Cholesterin zurück

aus Wikipedia, der freien Enzyklopädie

Das Cholesterin ist eine Kohlenstoffverbindung, die den Fetten zugerechnet wird. Der Name leitet sich davon ab, dass Gallensteine meist große Mengen an Cholesterin enthalten (griechisch: Chole = Galle und stereos = fest).

In Pflanzenölen kommt es nicht vor.

Beim Menschen wird Cholesterin zum Großteil selber in der Leber und im Gehirn produziert (ca. 700 mg/Tag), zum kleineren Teil mit der Nahrung aufgenommen.

Funktion

Cholesterin ist ein wichtiger Bestandteil aller Zellmembranen und stellt den Ausgangsstoff für die Bildung von Gallensäuren, Hormonen und Vitamin D dar, ist also in richtigen Mengen ein unverzichtbarer Grundbaustein für den ganzen Körper.

Synthese

Die Synthese des scheibenförmigen Moleküls erfolgt über jeweils 3 aktiviert Essigsäurereste (Acetylcoenzym A) und über viele Zwischenstufen. Im Blut liegt es teilweise verestert mit Fettsäuren vor.

Blutspiegel

Cholesterin ist im Blut nicht löslich und braucht daher eine wasserlösliche Hülle aus Fett und Eiweiß, genannt Lipoprotein.

Bilder

Cholesterinkristall

Cholesterin im Plaque

chemische Struktur

Zusammenhang cholesterin HI Häufigkeit

Spiegelverlauf unter Cholesterinsenker

Interventionsstudien

Leptin

Cholesterinkreislauf

HDL

LDL

Planetenreihe

Plaque im Sono

Das "gute" und das "schlechte" Cholesterin

Das HDL-Cholesterin (High Density Lipoprotein) ist das "gute" Cholesterin, weil es einen Schutzfaktor gegen Gefäßverkalkungen und somit gegen den Herzinfarkt darstellt. Es transportiert das Cholesterin von den Gefäßen weg zur Leber zurück.

Das Cholesterin ist für Tiere und den Menschen ein lebenswichtiger Stoff, da jeder Mensch in seinem Körper Cholesterin synthetisiert.

Es gibt Menschen, die bei ihrer Ernährung völlig auf tierische Produkte inklusive Eier und Milch verzichten (Veganer) und somit kein Cholesterin mit der Nahrung aufnehmen. Solange sie auf eine ausreichende Vitamin- und Spurenelementzufuhr achten, hat der völlige Verzicht auf Cholesterin wahrscheinlich keine negativen Konsequenzen.

Die Höhe des Cholesterinspiegels hängt von der körpereigenen Produktion, von der äußeren Zufuhr mit der Nahrung und vom Verbrauch z. B. durch körperliche Bewegung ab. Bei der Mehrzahl der Menschen mit erhöhtem Cholesterinwert ist dieser Folge sowohl einer erhöhten Zufuhr mit der Nahrung, als auch eines verminderten Verbrauches bei mangelnder körperlicher Bewegung. Cholesterin kommt in den Organen in bedeutenden Mengen vor.

Das "böse", weil Gefäß schädigende Cholesterin, nennt sich LDL-Cholesterin (Low Density Lipoprotein).

Das Gesamt-Cholesterin im Blut sollte kleiner als 200 mg/100 ml, das HDL sollte größer als 35 mg HDL und das LDL sollte kleiner als 120 mg sein.

Das zu hohe Cholesterin im Blut ist (bei Männern) ein wesentlicher Risikofaktor für den Herzinfarkt, den Schlaganfall und andere Durchblutungsstörungen.

Das American National Heart, Lung and Blood-Institute führte Metastudien zum gesundheitlichen Nutzen der Cholesterinsenkung durch. 19 Studien wurden analysiert. Untersucht wurden 650 000 Menschen und 70 000 Todesfälle: Geringe Cholesterinspiegel gehen nicht mit einer allgemeinen Erhöhung der Lebenserwartung einher, sondern beziehen sich nur auf Herz-Kreislauferkrankungen, sie erhöhen das Risiko von Schlaganfällen und das Krebsrisiko. Durch eine Verringerung senkt sich auch der Serotoninspiegel ab und führt zu schlechter Stimmung unter Umständen sogar bis zur Selbsttötung.

Der Einfluss der Nahrungsfette auf den Cholesterinspiegel ist bei sehr vielen Menschen sehr gering. So hat die eine prospektive Studie, die Verbundstudie Ernährungserhebung und Risikofaktoren Analytik (VERA, von 1985-1988 mit 25.000 Teilnehmern) ergeben, dass auch bei verschiedenen Mengen von gesättigten, aber auch ungesättigten Fettsäuren sowohl die HDL-, als auch die LDL-Werte sich, wenn überhaupt, nur minimal änderten. Da das Cholesterin ein lebenswichtiger Stoff ist, hängt die Höhe des Cholesterinspiegels im Wesentlichen nicht von der Nahrungszufuhr ab, der Großteil wird synthetisiert.

Es gibt erbliche Störungen des Cholesterinstoffwechsels (familiäre Hypercholesterinämie), die unabhängig von der Nahrungsaufnahme zu stark erhöhten Cholesterinwerten im Blut führen. Träger dieser Erbfaktoren sind durch Herzinfarkte und andere Gefäßkrankheiten schon in jüngeren Jahren betroffen. Diese erblichen Formen des hohen Cholesterinspiegels sind zumindest in der reinerbigen Form eher selten.

Nutzen der Lipidtherapie

Antonio M. Gotto, New York, stellte zu Beginn seiner Ausfuehrungen die provokante, wenn auch rhetorische Frage, ob es sich bei der Cholesterin-Geschichte um eine Art Mafia-Story handle, in der es um eine Verschwörung von Ärzten und Pharmaindustrie gehe. Die Antwort auf seine Frage gibt die Forschung

der vergangenen Jahre und Jahrzehnte.

Sie hat in verschiedenen Studien einen kaum mehr zu negierenden kausalen Zusammenhang zwischen Serumlipidspiegel und Koronarrisiko nachgewiesen.

Es begann mit Studien zur Wirksamkeit von reinen Diätinterventionen (z.B. die Life-style Heart Study oder die Lion Heart Study). Die Resultate solcher sekundär-präventiver Massnahmen fielen mässig positiv aus. Entscheidend für die heutige Sicht der Lipidsenkung mit Pharmaka waren dann die Ergebnisse grosser primär-präventiver Studien wie der Helsinki Heart Studie oder der WOSCOPS (West of Scotland

Coronary Prevention Study) und sekundär-präventiv angelegter Studien wie der 4S- Studie (Scandinavian Simvastatin Survival Study) oder des Long term Intervention with Pravastatin in Ischemic Disease (LIPID)

trial. Sie haben die aktuellen Empfehlungen zur Lipidsenkung massgeblich geprägt. Alle Studien, so Gotto, endeten mit einer deutlichen relativen, wenn auch einer etwas weniger ausgeprägten absoluten Risikoreduktion. Die numbers needed to treat (NNT) im Hinblick auf die Verhütung koronarer Ereignisse liegen bei den erwähnten Studien zwischen 12 und 50

Fragen

Warum geht die Zahl der Herzinfarkttoten zurück , gleichzeitig steigt aber Zahl der Übergewichtigen und der durchschnittliche Cholesterinspiegel weiter an ?

führte die Anwendung der Framingham-Risikoformel bei Teilnehmern der PROCAM-Studie zu einer 2,5fachen Überschätzung des Herzinfarktrisikos - unter anderem deshalb, weil die US-Studie zu einer Zeit durchgeführt wurde, als die Herzinfarktrate deutlich höher war als jetzt.

"Für die Praxis bedeutet das, dass einerseits Personen behandelt werden, die einer Behandlung nicht bedürfen, andererseits Personen eine Therapie vorenthalten wird, obwohl diese davon profitieren würden",

"Es gibt keinen Normalwert für alle Menschen. Für Personen mit dem höchsten Risiko ist ein LDL-Cholesterin unter 100 mg/dl für erstrebenswert, für Personen mit mittlerem Risiko gelten 130 mg/dl und bei Personen mit niedrigem Risiko 160 mg/dl als normal."

Weniger als ein Drittel der Hochrisikopatienten nahm einen Cholesterin-Senker ein, wobei insbesondere Diabetiker, ältere Menschen, Schlaganfall-Patienten und Frauen viel zu selten behandelt wurden", sagte der Leiter des ACOS-Registers, Prof. Jochen Senges (Ludwigshafen), in Düsseldorf. Von den Patienten ohne Statintherapie verstarben 7,2 Prozent im Vergleich zu 5,5 Prozent der Statin-Patienten; bei den Koronarkranken beziehungsweise Patienten mit KHK-Äquivalent waren es sogar 10,0 versus 6,3 Prozent (p = < 0,01). RV

Nach Ansicht der Autoren rechtfertigt die Datenlage (4-S-Studie, Scandinavian Simvastatin Survival Study; CARE-Studie, Cholesterol and Recurrent Events Study; WOS-Studie, West of Scotland Coronary Prevention Study) die Anwendung von Statinen im Rahmen der Sekundärprävention (unabhängig vom Risikoprofil) und im Rahmen der Primärprävention (bei hohen LDL-Werten und zusätzlichen Risikofaktoren).
Sie begründen ihre Aussage mit sehr hohen Werten bei der Senkung von bestimmten Ereignissen. So soll Simvastatin im Vergleich zu Plazebo "zu einer 30prozentigen Reduktion der Gesamt- und > 40prozentigen Reduktion der koronaren Mortalität führen". Auch Ballondilatationen und Bypass-Operationen sollen "um über 35 Prozent reduziert werden".
Mit diesen Aussagen irren die Autoren gewaltig: Die wahren Werte der Ereignisreduktion liegen bei 3,3 Prozent, 3,5 Prozent beziehungsweise 6 Prozent. Bei den von der Pharma-Industrie bevorzugten und optisch eindrucksvoll hohen Werten über 30 Prozent handelt es sich um die sogenannte Risikoreduktion. Diese interessiert den Arzt aber überhaupt nicht. Ihn interessiert nur die Reduktion der Ereignisse, und diese Zahlen sind wesentlich weniger spektakulär. Trotzdem rechtfertigen sie eine Sekundärprävention.

Primärprävention mit Lovastatin greift

Bereits beim letzten Kongreß der American Heart Association wurden erste Ergebnisse der Air Force Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) vorgestellt: Die Einnahme von Lovastatin über im Mittel fünf Jahre hatte das relative Risiko für ein kardiovaskulär bedingtes Ereignis (instabile Angina pectoris, tödlicher/überlebter Myokardinfarkt, plötzlicher Herztod) um 37 Prozent (p = 0,00008) reduziert. Dies war vor allem deswegen beeindruckend, weil es sich um eine - doppelblind randomisierte, plazebokontrollierte - Untersuchung zur Primärprävention gehandelt hatte. Die 6 605 eingeschlossenen Personen im Alter von 45 bis 75 Jahren wiesen bei Studienbeginn keinerlei Anzeichen einer koronaren Herzkrankheit auf, und die Gesamt-/LDL-Cholesterin-Werte waren nicht pathologisch. Einziger Hinweis auf ein potentiell erhöhtes Risiko war die HDL-Konzentration, die im Durchschnitt bei nur 37 mg/dl lag. Inzwischen liegt die Endauswertung von AFCAPS/TexCAPS vor. Studienleiter Dr. Antonio Gotto (New York) hielt es für besonders wichtig, darauf hinzuweisen, daß von der Lovastatin-Prophylaxe nicht nur individuelle Patienten profitieren, sondern das Gesundheitssystem als Ganzes. Denn mit der reduzierten Morbidität ging auch ein verminderter Bedarf an diagnostischen (um 23 Prozent) und therapeutischen (um 32 Prozent) Interventionen einher. bl-ki

Lancet. 2001 Aug 4;358(9279):351-5.

Related Articles, Links

Comment in:

Lancet. 2001 Dec 1;358(9296):1903-4; author reply 1906.

Lancet. 2001 Dec 1;358(9296):1904-5; author reply 1906.

Lancet. 2001 Dec 1;358(9296):1904; author reply 1906.

Lancet. 2001 Dec 1;358(9296):1905-6.

Lancet. 2001 Dec 1;358(9296):1905; author reply 1906.

Lancet. 2001 Dec 1;358(9296):1906-7.

Lancet. 2001 Dec 1;358(9296):1907.

Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.

Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD.

Clinical Epidemiology and Geriatrics Division, Department of Medicine, John A Bums School of Medicine, University of Hawaii at Manoa, 1356 Lusitana Street, 7th Floor, Honolulu, HI 96813-2427, USA. schatzi@hawaii.edu

BACKGROUND: A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS: Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS: Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

PMID: 11502313 [PubMed - indexed for MEDLINE]

Gibt es einen Cholesterinmangel ?

Wann gibt es niedrige Cholesterinspiegel ?

Was bringen Cholesterin infusionen ?

Am J Med Genet. 1997 Jan 31;68(3):305-10.

Comment in:

Am J Med Genet. 1998 Jul 24;78(4):378-80.

Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS)

Elias ER, Irons MB, Hurley AD, Tint GS, Salen G.

Department of Pediatrics, Tufts-New England Medical Center, Boston, Massachusetts, USA.

We describe the clinical effects of cholesterol supplementation in 6 children with the RSH-"Smith-Lemli-Opitz" syndrome (SLOS). The children ranged in age from birth to 11 years at the onset of therapy, with pretreatment cholesterol levels ranging from 8 to 62 mg/dl. Clinical benefits of therapy were seen in all patients, irrespective of age at onset of treatment, or severity of cholesterol defect. Effects of treatment included improved growth, more rapid developmental progress, and a lessening of problem behaviors. Pubertal progression in older patients, a better tolerance of infection, improvement of gastrointestinal symptoms, and a diminution in photosensitivity and skin rashes were also noted. There were no adverse reactions to treatment with cholesterol. This preliminary study suggests that cholesterol supplementation may be of benefit to patients with the SLOS.

Publication Types:

Clinical Trial

PMID: 9024564 [PubMed - indexed for MEDLINE]

J Intern Med. 2002 Oct;252(4):314-21.

Related Articles, Links

Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome.

Starck L, Lovgren-Sandblom A, Bjorkhem I.

Sachs' Children's Hospital, S-11883 Stockholm, Sweden. lena.starck@sos.sll.se

OBJECTIVES: To investigate if exogenous cholesterol affects sterol turnover in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome (SLOS) and if clinical effects justify long-time supplementation. The SLOS is caused by a deficiency of the enzyme 7-dehydrocholesterol-7-reductase with markedly reduced cholesterol levels and greatly increased levels of 7-dehydrocholesterol (7-DHC). DESIGN: Treatment with dietary cholesterol in patients with SLOS in a case series study. SETTING: All biochemical analyses were performed in one laboratory. The clinical follow-up was carried out by one of the authors (LS), a paediatric neurologist. SUBJECTS: Seven patients with biochemically verified SLOS have been diagnosed in Sweden and all of them are included in the study. INTERVENTIONS: Six patients were treated for 0.5-6 years orally with cholesterol and the bile acid taurocholate and one patient was supplemented with cholesterol only. MAIN OUTCOME MEASURES: In addition to cholesterol, 7- and 8-DHC, lathosterol was used as a marker of endogenous cholesterol synthesis and the patients were followed clinically. Nerve conduction velocities (NCV) were measured before treatment in all patients and a UVA-light test was performed in one of them. RESULTS: Lathosterol was initially increased by cholesterol supply in subjects with very low cholesterol levels with subsequent rise of 7- and 8-DHC. Photosensitivity clinically improved in all, verified by UVA-light testing in one. Progressive polyneuropathy improved, whilst stationary forms did not. CONCLUSION: Dietary cholesterol can up-regulate sterol turnover in severely affected patients. Although some specific features are treatable and verifiable by objective methods, data supporting life-long treatment dietary cholesterol in all SLO patients are still lacking.

Publication Types:

Clinical Trial

PMID: 12366604 [PubMed - indexed for MEDLINE]

Mol Genet Metab. 2000 Sep-Oct;71(1-2):163-74.

Related Articles, Links

RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis.

Porter FD.

Heritable Disorders Branch, National Institutes of Health, Bethesda, Maryland 20892-1830, USA.

The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome caused by an inborn error of cholesterol biosynthesis. The RSH/SLOS phenotypic spectrum is broad; however, typical features include microcephaly, ptosis, a small upturned nose, micrognathia, postaxial polydactaly, second and third toe syndactaly, genital anomalies, growth failure, and mental retardation. RSH/SLOS is due to a deficiency of the 3beta-hydroxysterol Delta(7)-reductase, which catalyzes the reduction of 7-dehydrocholesterol (7-DHC) to cholesterol. This inborn error of cholesterol biosynthesis results in elevated serum and tissue 7-DHC levels. The 3beta-hydroxysterol Delta(7)-reductase gene (DHCR7) maps to chromosome 11q12-13, and to date 66 different mutations of this gene have been identified in RSH/SLOS patients. Identification of the biochemical basis of RSH/SLOS has led to development of therapeutic regimens based on dietary cholesterol supplementation and has increased our understanding of the role cholesterol plays during embryonic development. Copyright 2000 Academic Press.

Publication Types:

Review

Review, Tutorial

PMID: 11001807 [PubMed - indexed for MEDLINE]

Können alle Zellen im Körper Cholesterin synthetisieren ?

Wenn nein , warum nicht ?

Wann taucht in der Evolution Cholesterin das erste mal auf ?

Warum haben Vegetarier einen niedrigen Cholesterinspiegel ?

Nahrungsbedingt ? Verhaltensbedingt ?

Warum leiden die Zellen bei der familiären Hypercholesterinämie nicht unter einem Cholesterinmangel ?

Wie äußert sich ein Cholesterinmangel ?

Was ist der Scavenger Weg der Cholesterinsenkung ?

In welchen Geweben findet sich viel Cholesterin ?

Warum steigt der durchschnittliche Cholesterinspiegel mit dem Alter ?

Welche Hormone beeinflußen den Cholesterinstoffwechsel ?

Links

• http://www.medizinfo.de/kardio/lipide/cholesterin.htm

Quellen

• M. Kohlmeier et al.: Verbreitung von klinisch-chemischen Risikoindikatoren in der BRD, Wiss. Fachverlag Dr. Fleck, VERA-Schriftenreihe BAND VII. Niederkleen 1993. M. Kestin et al. Effect of dietary cholesterol in normolipidemic subjects in not modified by nature and amount of dietary fat. American Journal of clinical Nutriation 1989/50/S.528. W.E.Stehbends: Diet and atherogenesis. Nutritions Reviews 1989/47/S.1 - zur Unabhängigkeit des Cholesterins von der Nahrung

• U. Ravnskov: Cholesterin lowering trials in coronary heart disease: frequency of citation and outcome. British Medical Journal 1993/305/S.15 - zum Einfluss des Cholesterins auf die Gesamtsterblichkeit

• Jörg Blech: Die Krankheitserfinder (S.78 ff.) - zur wirtschaftlichen Ausnutzung der Cholesterin-Phobi

Orginaltexte

DIE ZEIT

Cholesterin-Transporter von Darmzellen identifiziert

Wissenschaftler von Schering-Plough haben erstmalig ein Cholesterin-Transportprotein in Zellen der Dünndarmwand entdeckt. Die Aufnahme von Cholesterin aus der Nahrung in den Blutkreislauf könnte über diesen Transporters reguliert werden.

Auf der Suche nach dem Rezeptorprotein durchsuchten die Forscher öffentlich zugängliche DNA-Datenbanken von bei der Cholesterinaufnahme aktiven Darmzellen, den Enterocyten. Dabei erkannten sie Cholesterin bindende Strukturmotive an einem Protein, das sich auf der Zelloberfläche im Darminnenraum befindet. Als die Forscher dieses NPC1L1 genannte Eiweiß bei Mäusen durch ein Medikament gezielt blockierten, nahmen die Tiere nur noch knapp ein Drittel der üblichen Cholesterinmengen aus der Nahrung auf.

Gemeinsam mit körpereigenem, in der Leber produzierten Cholesterin beeinflusst aus der Nahrung stammendes Cholesterin den Cholesterinspiegel des Blutes. Hohe Blut-Cholesterinwerte werden mit verschiedenen Erkrankungen in Zusammenhang gebracht.

(c) wissenschaft-online / Quelle: Science 303: 1201-1204 (2004)

MRFIT Daten:

JAMA. 1986 Nov 28;256(20):2823-8.

Related Articles, Links

Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT).

Stamler J, Wentworth D, Neaton JD.

The 356,222 men aged 35 to 57 years, who were free of a history of hospitalization for myocardial infarction, screened by the Multiple Risk Factor Intervention Trial (MRFIT) in its recruitment effort, constitute the largest cohort with standardized serum cholesterol measurements and long-term mortality follow-up. For each five-year age group, the relationship between serum cholesterol and coronary heart disease (CHD) death rate was continuous, graded, and strong. For the entire group aged 35 to 57 years at entry, the age-adjusted risks of CHD death in cholesterol quintiles 2 through 5 (182 to 202, 203 to 220, 221 to 244, and greater than or equal to 245 mg/dL [4.71 to 5.22, 5.25 to 5.69, 5.72 to 6.31, and greater than or equal to 6.34 mmol/L]) relative to the lowest quintile were 1.29, 1.73, 2.21, and 3.42. Of all CHD deaths, 46% were estimated to be excess deaths attributable to serum cholesterol levels 180 mg/dL or greater (greater than or equal to 4.65 mmol/L), with almost half the excess deaths in serum cholesterol quintiles 2 through 4. The pattern of a continuous, graded, strong relationship between serum cholesterol and six-year age-adjusted CHD death rate prevailed for nonhypertensive nonsmokers, nonhypertensive smokers, hypertensive nonsmokers, and hypertensive smokers. These data of high precision show that the relationship between serum cholesterol and CHD is not a threshold one, with increased risk confined to the two highest quintiles, but rather is a continuously graded one that powerfully affects risk for the great majority of middle-aged American men.

Cardiology. 1993;82(2-3):181-90.

Related Articles, Links

Does the predictive value of baseline coronary risk factors change over a 30-year follow-up?

Pekkanen J, Tervahauta M, Nissinen A, Karvonen MJ.

Department of Environmental Epidemiology, National Public Health Institute, Kuopio, Finland.

The association of baseline serum total cholesterol, systolic blood pressure, smoking and body mass index with coronary heart disease (CHD) mortality was analyzed among 1,619 men aged 40-59 at baseline. Analyses were made separately for the first, second and third decade of follow-up. Serum cholesterol and smoking more than 9 cigarettes daily were strong predictors of risk of CHD death (n = 450) occurring early and late during the 30-year follow-up. After 20 years of follow-up, systolic blood pressure was no longer associated with CHD risk. In contrast, highest tertile of body mass index (over 24.7 kg/m2) was only then associated with increased CHD risk. The correlations between the baseline and the 30-year risk factor values were 0.42 for serum cholesterol (n = 444), 0.28 for systolic blood pressure (n = 444) and 0.57 for body mass index (n = 429). Our results showed large differences in the long-term predictive power of the classical coronary risk factors. The reasons for these differences are discussed.

PMID: 3773199 [PubMed - indexed for MEDLINE]

Arch Intern Med. 1992 Jul;152(7):1490-500.

Related Articles, Links

Comment in:

Arch Intern Med. 1993 May 24;153(10):1268, 1271.

Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.

Neaton JD, Blackburn H, Jacobs D, Kuller L, Lee DJ, Sherwin R, Shih J, Stamler J, Wentworth D.

Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis 55414.

BACKGROUND--With increased efforts to lower serum cholesterol levels, it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease, for which an etiologic relationship has been established. METHODS--For an average of 12 years, 350,977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single standardized measurement of serum cholesterol level and other coronary heart disease risk factors; 21,499 deaths were identified. RESULTS--A strong, positive, graded relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease. This relationship persisted over the 12-year follow-up period. No association was noted between serum cholesterol level and stroke. The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke. For the latter, a positive, graded association with serum cholesterol level was evident. For intracranial hemorrhage, cholesterol levels less than 4.14 mmol/L (less than 160 mg/dL) were associated with a twofold increase in risk. A serum cholesterol level less than 4.14 mmol/L (less than 160 mg/dL) was also associated with a significantly increased risk of death from cancer of the liver and pancreas; digestive diseases, particularly hepatic cirrhosis; suicide; and alcohol dependence syndrome. In addition, significant inverse graded associations were found between serum cholesterol level and cancers of the lung, lymphatic, and hematopoietic systems, and chronic obstructive pulmonary disease. No significant associations were found of serum cholesterol level with death from colon cancer, with accidental deaths, or with homicides. Overall, the inverse association between serum cholesterol level and most cancers weakened with increasing follow-up but did not disappear. The association between cholesterol level and death due to cancer of the lung and liver, chronic obstructive pulmonary disease, cirrhosis, and suicide weakened little over follow-up. CONCLUSIONS--The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence. Further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease, whether serum cholesterol level and noncardiovascular disease are both consequences of other factors, or whether these associations are causal.

Publication Types:

Clinical Trial

Multicenter Study

Randomized Controlled Trial

: BMJ. 1989 Jul 8;299(6691):81-5.

Related Articles, Links

Risk factors and 25 year risk of coronary heart disease in a male population with a high incidence of the disease: the Finnish cohorts of the seven countries study.

Pekkanen J, Nissinen A, Puska P, Punsar S, Karvonen MJ.

Department of Epidemiology, National Public Health Institute, Helsinki, Finland.

OBJECTIVE--To assess the efficacy of high serum cholesterol concentration, raised blood pressure, and smoking as predictors of coronary heart disease. DESIGN--Prospective cohort study of middle aged men conducted over 25 years. SETTING--Finish components of an ongoing international study (seven countries study). PARTICIPANTS--1520 Men who at age 40-59 in 1959 were free of clinically evident heart disease. INTERVENTIONS--At each follow up visit a detailed medical examination including resting electrocardiography was performed, blood pressure and serum total cholesterol concentration were measured, and smoking was assessed. MEASUREMENTS AND MAIN RESULTS--825 Deaths (54% of participants) occurred during follow up, of which 335 were due to coronary heart disease. The hazard ratio for death from coronary heart disease with respect to risk factors at entry were: for serum cholesterol concentrations above 8.4 mmol/l v below 5.2 mmol/l, 2.68 (95% confidence interval 1.62 to 4.42); for systolic blood pressure in the highest quintile v that in the lowest quintile, 2.46 (1.72 to 3.50); and for smoking 10 or more cigarettes daily v never smoking, 1.95 (1.36 to 2.79). The hazard ratios with respect to cholesterol concentrations and blood pressure remained constant during follow up but the ratio with respect to smoking diminished, mainly owing to men giving up the habit. The estimated conditional probability of a 50 year old man dying of coronary heart disease in the next 25 years ranged from 12% among those with the most favourable risk factor profile to 75% among those with the least favourable profile. CONCLUSIONS--High risk factor levels (as determined in this study) in middle aged men may greatly increase the absolute probability of death from coronary heart disease when the period of study is relevant to the human life span.

PMID: 2504340 [PubMed - indexed for MEDLINE]

Monica

Z Kardiol. 2003 Jun;92(6):445-54.

Related Articles, Links

[Classical risk factors for myocardial infarction and total mortality in the community--13-year follow-up of the MONICA Augsburg cohort study]

[Article in German]

Heidrich J, Wellmann J, Hense HW, Siebert E, Liese AD, Lowel H, Keil U.

Institut fur Epidemiologie und Sozialmedizin, Universitat Munster, Domagkstr. 3, 48129 Munster, Germany. heidricj@uni-muenster.de

PURPOSE: The MONICA (MONItoring of trends and determinants in CArdiovascular disease) project in the region of Augsburg, Southern Germany, is the first population-based cohort study in Germany investigating the association of the risk factors hypertension, hypercholesterolemia and smoking with incident myocardial infarction and total mortality, and to assess their impact at the population level. METHODS: At baseline, 1074 men and 1013 women aged 45-64 years were randomly selected from the population in the Augsburg region and extensively interviewed and examined regarding their cardiovascular risk profile. They were traced over 13 years from 1984-1997. We calculated incidence rates, hazard rate ratios, population attributable risks (PAR), and rate advancement periods (RAP) according to the three risk factors and their combinations. RESULTS: Among men, 107 myocardial infarctions and 204 total mortality events occurred during the study period; in women the number of total mortality cases was 102. The three classical risk factors were associated with incident myocardial infarction in men and with total mortality in men and women over a period of 13 years. Heavily smoking men had a particularly high risk of total mortality (HRR=4.2; 95% CI 2.5-7.0) and myocardial infarction (HRR=3.8; 1.9-7.6). Men with treated hypertension were at equally high risk for both total mortality (HRR=2.4; 1.5-3.7) and myocardial infarction (HRR=2.4; 1.3-4.3). In women, treated hypertension (HRR=2.5; 1.5-4.1) and hypercholesterolemia (HRR=2.0; 1.2-3.3) were most strongly related to total mortality. Regarding the association of risk factor combinations and myocardial infarction among men, the presence of all three risk factors simultaneously (HRR=7.9; 3.6-17.3) and the combination smoking/hypercholesterolemia (HRR=5.8; 3.2-10.5) were particularly hazardous. In total, the three risk factors contributed 54% of the burden of myocardial infarction in the male study population. The rate advancement periods for myocardial infarction related to treated hypertension, hypercholesterolemia and heavy smoking were 10.5, 5.8 and 15.8 years, respectively. CONCLUSIONS: Our results confirm the outstanding impact of the classical risk factors on myocardial infarction and total mortality in a southern German population. Coronary heart disease is largely preventable through risk factor reduction. Therefore, risk factor counselling, education and treatment are crucial to prevent people from developing the disease or dying prematurely.

PMID: 12819993 [PubMed - indexed for MEDLINE]

Eur Heart J. 2003 May;24(10):937-45.

Related Articles, Links

Comment in:

Eur Heart J. 2003 Oct;24(19):1796; author reply 1796-7.

Framingham risk function overestimates risk of coronary heart disease in men and women from Germany--results from the MONICA Augsburg and the PROCAM cohorts.

Hense HW, Schulte H, Lowel H, Assmann G, Keil U.

Institute of Epidemiology and Social Medicine, University Muenster, D 48129, Muenster, Germany. hense@uni-muenster.de

BACKGROUND: The prediction of the absolute risk of coronary heart disease (CHD) is commonly based on risk prediction equations that originate from the Framingham Heart Study. However, differences in population risk levels compromise the external validity of these risk functions. SETTING AND STUDY POPULATION: Participants aged 35-64 years from the MONICA Augsburg (2861 men and 2925 women) and the PROCAM (5527 men and 3155 women) cohorts were followed-up with regard to incident non-fatal myocardial infarction (MI) and fatal coronary events. For each participant, the predicted absolute risk of fatal plus non-fatal events was derived using Framingham risk equations. Predicted and actually observed risks were compared. RESULTS: The two cohorts were similar in their baseline characteristics. Coronary risk predicted by the Framingham risk function substantially exceeded the risk actually observed in the German cohorts, irrespective of gender. The difference between predicted and observed absolute CHD risk increased with age while the ratio of predicted over observed risk remained constant at about a value of 2. Taking potentials for underascertainment in the German cohorts due to unrecognised MI and sudden deaths into account, the residual magnitude of risk overestimation by the Framingham risk function is probably at least 50%. CONCLUSIONS: Local guidelines for the management of patients with risk factors need to correct for this overestimation to avoid inadequate initiation of treatment and inflation of costs in primary prevention. Similar studies should be conducted in other populations with the aim of defining appropriate factors that calibrate absolute risk predictions to local population levels of CHD risk.

Publication Types:

Multicenter Study

Validation Studies

Eur J Nutr. 2001 Dec;40(6):282-8.

Related Articles, Links

Five year changes in waist circumference, body mass index and obesity in Augsburg, Germany.

Liese AD, Doring A, Hense HW, Keil U.

Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia 29208, USA. ALIESE@sph.sc.edu

AIMS: To assess temporal changes in body fat distribution, body mass index and obesity in Augsburg, Germany. METHODS: Waist circumference, weight and height were measured in two independent samples of 4804 and 4792, men and women, aged 25-74 years, in the MONICA Augsburg surveys 1989/90 and 1994/95. Abdominal obesity was defined as waist circumference greater than the 80th gender-specific percentile (men: 103, women: 92 cm) in the 1989/90 population. Obesity was defined as a body mass index (BMI) > or = 30 kg/m2. RESULTS: Age-standardized mean waist circumference increased by more than 1 cm (p-value < 0.00003) in both men and women while BMI increased by 0.3-0.4 kg/m2 (p-value < 0.01). We observed both a shift to higher values in the waist circumference distribution plus--particularly in women older than 45 years --a substantial right shift in the top of the distribution. Moreover, survey participants in 1994/95 who were at the higher end of the BMI distributions were disproportionately more obese than their respective peers in 1989/90. The prevalence of abdominal obesity rose by 3.3% in men and 3.6% in women, while the prevalence of obesity rose by 2% from 17% in men and by 2.5% from 19% in women. CONCLUSIONS: While changes in the Augsburg population may not be as alarming as in other countries, the secular increase in waist circumferences in both men and women occurring over a short time period indicates a need for prevention given the already high absolute weight, BMI and waist circumference levels in the population.

PMID: 11876492 [PubMed - indexed for MEDLINE]

Epidemiology. 1999 Jul;10(4):391-7.

Related Articles, Links

Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases.

Liese AD, Hense HW, Lowel H, Doring A, Tietze M, Keil U.

Institute of Epidemiology and Social Medicine, University of Munster, Germany.

Because previous findings have been inconsistent, we explored the association of serum concentrations of uric acid with all-cause and cardiovascular disease mortality and myocardial infarction prospectively. We used data from 1,044 men who are members of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) Augsburg cohort. The men, 45-64 years of age in 1984-1985, were followed through 1992. There were 90 deaths, 44 of which were related to cardiovascular disease; 60 men developed incident nonfatal or fatal myocardial infarction. We estimated hazard rate ratios from Cox proportional hazard models. Uric acid levels > or =373 micromol/liter (fourth quartile) vs < or =319 micromol/liter (first and second quartile) independently predicted all-cause mortality [hazard rate ratio = 2.8; 95% confidence interval (CI) = 1.6-5.0] after adjustment for alcohol, total cholesterol/high-density lipoprotein cholesterol ratio, hypertension, use of diuretic drugs, smoking, body mass index, and education. The adjusted risk of cardiovascular disease mortality was 2.2 (95% CI = 1.0-4.8), and that of myocardial infarction was 1.7 (95% CI = 0.8-3.3). Although residual confounding cannot be excluded, our results are among the few, in men, demonstrating a strong positive association of elevated serum uric acid with all-cause mortality. Future investigations may be able to evaluate whether uric acid contributes independently to the development of cardiovascular disease or is simply a component of the atherogenic metabolic condition known as the insulin resistance syndrome.

PMID: 10401873 [PubMed - indexed for MEDLINE]

1: Eur Heart J. 1998 Aug;19(8):1197-207.

Related Articles, Links

Classical risk factors and their impact on incident non-fatal and fatal myocardial infarction and all-cause mortality in southern Germany. Results from the MONICA Augsburg cohort study 1984-1992. Monitoring Trends and Determinants in Cardiovascular Diseases.

Keil U, Liese AD, Hense HW, Filipiak B, Doring A, Stieber J, Lowel H.

Institute of Epidemiology and Social Medicine, University of Munster, Germany.

BACKGROUND:The MONICA (Monitoring Trends and Determinants in Cardiovascular Diseases) project in Augsburg provides the first population-based cohort study in Germany to quantify the associations of the risk factors hypertension, hypercholesterolaemia and smoking with incident non-fatal and fatal myocardial infarction and all-cause mortality, and to assess their impact at the population level. METHODS: The cohort comprises 1074 men and 1013 women aged 45-64 years; they were followed over 8 years from 1984-1992. In the men, there were 61 non-fatal and fatal myocardial infarctions and 92 all-cause mortality events over this period; in the women the number of deaths from all causes was 45. Incidence rates, hazard rate ratios, population attributable fractions and rate advancement periods were calculated. RESULTS: Adjusting for confounders, the myocardial infarction hazard rate ratios for men with hypertension, or a total cholesterol/HDL-cholesterol ratio > or =5.5, or smoking > or =20 cigarettes/day, were 2.0 (95% CI 1.2-3.5), 2.9 (95%, CI 1.7-5.0), and 2.7 (95% confidence interval (CI) 1 4-5.0), respectively. The risk factor combination total cholesterol/HDL cholesterol ratio > or = 5.5 and cigarette smoking was particularly hazardous. The three risk factors contributed 65% of the burden of myocardial infarction in the population. The rate advancement period for myocardial infarction associated with hypertension, total cholesterol/HDL cholesterol ratio > or =5.5 or smoking > or =20 cigarettes/day was 8.3, 12.4 and 11.5 years, respectively. In women, these risk factors were similarly predictive of all-cause mortality. Comparing the cohort data from Augsburg with those of two occupational cohorts from Germany reveals higher absolute myocardial infarction risks in the Augsburg population; however, the relative risk estimates in the Augsburg and the two occupational cohorts were very similar. CONCLUSION: Our results confirm the important contribution of the classical risk factors to the risk of myocardial infarction and all-cause mortality in Germany. The results pertaining to the concept of rate advancement periods particularly demonstrate the great potential for prevention.

PMID: 9740341 [PubMed - indexed for MEDLINE]

Ann Epidemiol. 1991 Nov;1(6):487-92.

Related Articles, Links

Comment in:

Ann Epidemiol. 1991 Nov;1(6):567-9.

Weight change and change of total cholesterol and high-density-lipoprotein cholesterol. Results of the MONICA Augsburg cohort study.

Eberle E, Doering A, Keil U.

GSF-Forschungszentrum fur Umwelt und Gesundheit (GSF), Institute of Epidemiology, Neuherberg, Federal Republic of Germany.

Data from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg cohort were used to study the effect of weight change on changes in serum levels of total and high-density-lipoprotein cholesterol. Weight gain was associated with rising levels of total cholesterol and falling levels of high-density-lipoprotein cholesterol in both sexes, more so in men than in women. Moreover, these relationships weakened with advancing age in women, but not in men. The results support the view that weight loss may more favorably affect lipid levels in men than in women, particularly at older ages.

PMID: 1669528 [PubMed - indexed for MEDLINE]

Ann Nutr Metab. 1991;35(5):284-91.

Related Articles, Links

1: Rev Epidemiol Sante Publique. 1990;38(5-6):411-7.

Related Articles, Links

Morbidity and mortality of myocardial infarction in the Augsburg MONICA study area in 1985, 1986 and 1987.

Lowel H, Lewis M, Hormann A, Eberle E, Keil U.

GSF Munchen-Medis Institut, Neuherberg, FR Germany.

In the years 1985, 1986 and 1987, the MONICA Augsburg Coronary Event Register recorded 1488 coronary events (1214 men and 274 women) occurring in 35-64 year old residents of the study region (population: 102,000 men and 105,000 women). The rates presented include all coronary events with a definite acute myocardial infarct (AMI), possible AMI, resuscitated cardiac arrest, and insufficient data. The age-standardized attack rates in men are 390 (1985) to 372 (1987) and in women 51 (1985) to 72 (1987) per 100,000 population. The age-standardized 28-day case fatalities in men are 44 (1985) to 44 (1987) and in women 67 (1985) to 55 (1987) per 100 coronary events. With the exception of the attack rates in women, no statistically significant differences between yearly rates could be established.

PMID: 2082446 [PubMed - indexed for MEDLINE]

Selected nutrient intakes of middle-aged men in southern Germany: results from the WHO MONICA Augsburg Dietary Survey of 1984/85.

Winkler G, Doring A, Keil U.

GSF-Institut fur Epidemiologie, Neuherberg, BRD.

In the WHO MONICA Augsburg survey of 1984/85 dietary intake was assessed in an age-stratified cluster sample of 899 men aged 45-64 years by 7-day records. The mean energy intake was 2,609 kcal (10.9 MJ), 15.9% of which came from protein, 38.1% from fat, and 36.6% from carbohydrate. A remarkably high proportion of 9.4% was derived from alcohol. Saturated fatty acids accounted for 14.6% of total energy, monounsaturated fatty acids for 13.2% and polyunsaturated fatty acids for 5.2%. The results showed that current dietary habits do not conform with the national nutritional guidelines.

Soz Praventivmed. 1989;34(1):10-4.

Related Articles, Links

Awareness and treatment of hypercholesterolemia: results of the first survey of the MONICA Project Augsburg.

Doring A, Filipiak B, Winkler G, Keil U.

GSF-Medis Institut, Neuherberg bei Munchen.

In the first survey of the MONICA project Augsburg (1984/1985), awareness and treatment of hypercholesterolemia was determined on a two-stage cluster sample of 5069 25-64 year old citizens (participation 79.6%). Hypercholesterolemia was defined according to the Conference of the European Atherosclerosis Society (EAS) and of the National Cholesterol Education Program (NCEP). Awareness (elevated lipid levels found during the last 12 months), and drug and dietary treatment were determined by an interview. The awareness was low and varied between 4 and 24% in the different age-sex groups with no significant differences between sexes, with one exception: The awareness in women aged 55-64 years with cholesterol levels greater than or equal to 300 mg/dl was 38% and differed significantly from that found in men in the same age group (21%). Older participants showed a higher degree of awareness than younger; in men the awareness was independent from the cholesterol level, in women those with higher levels showed a better awareness than those with lower levels (results from a logistic regression analysis for cholesterol levels greater than or equal to 240 mg/dl). The use of lipid-lowering drugs was low in the study population (2% in men, 1% in women). The drug treatment of hypercholesterolemia was low and in no age-sex group higher than 7%, despite the definition of hypercholesterolemia; the dietary treatment was not higher than 20%. In conclusion it is shown, that there is a great need for the identification and management of hypercholesterolemia in the examined population in Southern Germany.

PMID: 2711758 [PubMed - indexed for MEDLINE]

Acta Med Scand Suppl. 1988;728:119-28.

Related Articles, Links

The cardiovascular risk factor profile in the study area Augsburg. Results from the first MONICA survey 1984/85.

Keil U, Stieber J, Doring A, Chambless L, Hartel U, Filipiak B, Hense HW, Tietze M, Gostomzyk JG.

GSF-Medis Institute, Munchen, F.R. Germany.

The main objective of the first survey was the investigation of the prevalence and distribution of hypertension, hypercholesterolemia and cigarette smoking in the study area. The data-collection phase lasted from October 1984 to May 1985. A two-stage cluster sample of 5312 persons of German nationality was drawn from a population of 282,279 inhabitants, aged 25-64. The data were gathered through interview, physical examination and self-administered questionnaire. A response of 79% was achieved. Sixteen percent of men and 10% of women had high blood pressure (BP) values (greater than or equal to 160/95 mmHg). Only 16% of male and 34% of female hypertensives had controlled BP values. The prevalence of hypercholesterolemia (greater than or equal to 6.72 mmol/L = greater than or equal to 260 mg/dl) was 26% in men and 22% in women. Forty percent of men and 22% of women reported they were current cigarette smokers. Among participants, aged 25-44, cigarette smoking was the most prevalent risk factor in men and women. Thirty-seven percent of men and 52% of women, aged 25-64, had none of the three major risk factors.

PMID: 3264450 [PubMed - indexed for MEDLINE]

Soz Praventivmed. 1988;33(1):17-21.

Related Articles, Links

Morbidity and mortality of myocardial infarction in the MONICA study area Augsburg in 1985.

Lowel H, Keil U, Koenig W, Hormann A, Lewis M, Bolte HD, Gostomzyk J.

GSF-Medis-Institut, Neuherberg.

In the year 1985, 998 (734 men, 264 women) cases of acute coronary events were registered among the 25-74 year-old residents of the study area (151,489 men and 171,093 women) of whom 583 (403 men, 180 women) died within 28 days (case fatality). Both AMI as a clinical diagnosis and AMI as a cause of death are validated by defined MONICA diagnostic criteria (acute symptoms, enzyme level, ECG, autopsy diagnosis). The AMI-risk (MONICA diagnostic categories 1, 2, 3, 9) in the study area Augsburg is relatively low (incidence: men 302, women 113; attack rate: men 444, women 138; death rate: men 241, women 92; all per 100,000 for each group). The 28-day case fatality is comparatively high (men 54%, women 67%). A comparison of the Augsburg rates with those of three other centers shows that the Augsburg figures are in the lower range.

Klin Wochenschr. 1988;66 Suppl 11:58-65.

Related Articles, Links

B-scan ultrasound examination of the carotid arteries within a representative population (MONICA Project Augsburg).

Gostomzyk JG, Heller WD, Gerhardt P, Lee PN, Keil U.

Gesundheitsamt der Stadt Augsburg.

As part of the MONICA project carried out in Augsburg, 1388 male and female subjects, aged 25 to 65 years, participated in a B-scan ultrasound examination of the carotid arteries. The segments of the carotid arteries examined on both sides of the neck were the A. carotis communis, the A. carotis interna, and A carotis externa. As a result plaques were found in 330 subjects (23.9%). The presence of plaques in subjects is strongly correlated to age (increasing trend in both sexes, P less than 0.001) and the process of establishing plaques starts in men earlier than in women (P less than 0.01). For both sexes a different correlation structures is found for the relationship of cardiovascular risk factors to presence of plaques as well as to number of plaques in the carotid arteries. In men, total cholesterol (P less than 0.05) and personal history of diabetes, myocardial infarction, and stroke (P less than 0.01) were positively correlated with the presence of plaques while HDL/total cholesterol ratio shows a negative correlation (P less than 0.01). In women, none of the analyzed risk factors is found to correlate significantly with the presence of plaques. Regarding the number of vessels with plaques, a consistent and significant relationship with both hypertension and total cholesterol is seen in males and with hypertension in females. Comparing the different factors analyzed, age is obviously much more related to the occurrence of plaques than all the other risk factors together. Age is followed by a decrease in HDL cholesterol and, at a much lower level, by hypertension and smoking.

PMID: 3054282 [PubMed - indexed for MEDLINE]

1: Arch Intern Med. 2002 Jan 14;162(1):82-9.

Related Articles, Links

Sex differences in risk factors for incident type 2 diabetes mellitus: the MONICA Augsburg cohort study.

Meisinger C, Thorand B, Schneider A, Stieber J, Doring A, Lowel H.

Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany. kora.augsburg@t-online.de

OBJECTIVE: To examine sex-specific associations between cardiovascular risk factors, a parental history of diabetes, and type 2 diabetes mellitus (DM). METHODS: The study is based on 3052 men and 3114 women (aged 35 to 74 years) who participated in one of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995, who were free of DM at baseline and returned a follow-up questionnaire in 1998. Sex-specific hazard ratios (HRs) were estimated from Cox proportional hazard models. RESULTS: A total of 128 cases of incident DM among men and 85 cases among women were registered during the follow-up period. The age-standardized incidence rate was 5.8 per 1000 person-years for men and 4.0 per 1000 person-years for women. In multivariable survival analyses, age, body mass index, and a positive parental history of diabetes were important independent risk factors for DM in both sexes. High-density lipoprotein cholesterol level was inversely associated with DM in men and women. For other risk factors, sex-related differences were observed. Systolic blood pressure (HR per 10 mm Hg increase, 1.16), regular smoking (HR, 1.75), and high daily alcohol intake (HR, 1.95) predicted the development of DM in men only, whereas uric acid (HR per 1 mmol/L increase, 2.05) and physical inactivity during leisure time (HR, 1.80) were associated with diabetes development in women only. CONCLUSIONS: In men and women, most variables predicting future diabetes in the present study are also known to be important risk factors for cardiovascular disease and arteriosclerosis. However, there are sex-related dissimilarities that seem to be involved in disease development.

PMID: 11784224 [PubMed - indexed for MEDLINE]

J Epidemiol Community Health. 2002 Feb;56 Suppl 1:i19-24.

Related Articles, Links

Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe.

Bots ML, Elwood PC, Nikitin Y, Salonen JT, Freire de Concalves A, Inzitari D, Sivenius J, Benetou V, Tuomilehto J, Koudstaal PJ, Grobbee DE.

Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands. M.L.Bots@jc.azu.nl

BACKGROUND: Controversy remains on the relation between serum lipids levels and stroke risk. This paper investigated the association of total and HDL cholesterol level to fatal and non-fatal, and haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and risk factors were available from cohorts in Cardiff (84 cases), Kuopio (74 cases), Rotterdam (157 cases), and Novosibirsk (79 cases). RESULTS: Pooled analyses showed no significant association between total cholesterol and risk of stroke (odds ratio for increase of 1 mmol/l in cholesterol of 0.98 (95% CI 0.88 to 1.09)). Analyses for haemorrhagic stroke and cerebral infarction revealed odds ratios of 0.80 (95% CI 0.61 to 1.05) and 1.06 (95% CI 0.94 to 1.19), respectively. The association of HDL cholesterol to stroke was different in men compared with women. In men, there was a general trend towards a lower risk of stroke with an increase in HDL (odds ratio per 1 mmol/l increase in HDL cholesterol 0.68 (95% CI 0.40 to 1.16)). In women, however, an increase in HDL was associated with a significant increased risk of non-fatal stroke and of cerebral infarction (odds ratios of 2.46 (95% 0.1.20 to 5.04) and 2.52 (95% CI 1.15 to 5.50), respectively. The difference between men and women in the association of HDL with stroke seemed to differ mainly in smokers and never smokers, but not among ex smokers. CONCLUSION: This analysis of the EUROSTROKE project could not disclose an association of total cholesterol with fatal, non-fatal, haemorrhagic or ischaemic stroke. HDL cholesterol however, seemed to be related to stroke differently in men than in women.

PMID: 11815640 [PubMed - indexed for MEDLINE]

Show:

Write to the Help Desk

NCBI | NLM | NIH

Department of Health & Human Services

Freedom of Information Act | Disclaimer

Jan 29 2004 15:06:34

Z Gerontol Geriatr. 1998 Jun;31(3):184-92.

Related Articles, Links

[Family status and social integration as predictors of mortality: a 5-year follow-up study of 55- to 74-year-old men and women in the Augsburg area]

[Article in German]

Baumann A, Filipiak B, Stieber J, Lowel H.

Institut fur Epidemiologie GSF-Forschungszentrum fur Umwelt und Gesundheit.

The relation between marital status, social integration and the mortality from all causes was examined in a population based cohort study. The 5-year-cohort consisted of 1,030 men and 957 women, aged 55-74 years who participated in the second MONICA Survey Augsburg, F.R.G., 1989/90 (MONICA = Monitoring of trends and determinants of cardiovascular disease). They were followed for mortality until 1995. Altogether 120 men and 45 women had died. Social integration was measured by an index of social ties. The index of social ties examined in these analyses includes (a) presence of a spouse, (b) number of close friends and relatives, (c) reported contact with close friends and relatives. Age standardized mortality rates (per 10,000 person years) were computed for men and women. Sex-specific Cox-proportional hazard models were used and hazard rate ratios (HRR) were calculated adjusting for age, hypertension, cigarette smoking, cholesterol, drinking alcohol, number of chronic diseases and self-reported health. Mortality rates were higher for men who were living alone (437.3) than for married men (235.3). Respectively in women the rates were 121.6 compared to 80.7. After controlling for age and self-reported health a HRR of 1.5 (95% CI: 1.0-2.4) was observed for single, divorced or widowed men and a HRR of 1.6 (95% CI: 0.8-3.0) for women living alone. Low mortality rates were observed in people with many social ties (men: 180.1, women: 29.9). Mortality rates of people who gave no informations about social ties (men: 349.5, women: 124.9) were similar to those who had only few social ties (men: 321.1, women: 132.5). The findings showed that people with few social ties were more likely to die in the follow-up period than those with more extensive contacts. After adjusting for age and self-reported health the HRR for those with few ties compared to those with many social ties were 1.6 (95% CI: 1.1-2.5) for men and 2.7 (95% CI: 1.1-6.6) for women. Similar results were found for people who gave no informations about their social ties (men: HRR = 1.4, 95% CI: 0.9-2.3; women: HRR = 2.6, 95% CI: 1.0-6.9). Social relationships were shown to be important predictors of mortality in elderly women and men. These findings confirm the need for further research, which enables to take steps against high mortality of the social isolated elderly.

PMID: 9702829 [PubMed - indexed for MEDLINE]

Eur Heart J. 1997 Aug;18(8):1220-30.

Related Articles, Links

ESC Population Studies Lecture 1996. Cardiovascular monitoring of a city over 30 years.

Wilhelmsen L.

Department of Medicine, Ostra University Hospital, Goteborg, Sweden.

This lecture on population studies was given in memory and honour of the late Professor Frederick Epstein. It relates to studies performed in Goteborg, Sweden. The main topics discussed in the presentation are: Coronary heart disease and stroke incidence according to the MONICA Project. Risk factors with special emphasis on relative and population attributable risk. Incidence and mortality of coronary heart disease in hospital and out of hospital. Quantitative aspects on treatment and prevention of myocardial infarction. The analysis was based upon a Myocardial Infarction Register which started in 1970, cross-sectional and prospective population studies primarily among men which started in 1963, cross-sectional studies among men and women based upon population studies (the MONICA Project) as well as studies of myocardial infarction. We have also been involved in many intervention trials in primary and secondary prevention regarding physical training, beta-blockers, thrombolytics, aspirin, anti-arrhythmics, ACE-inhibitors and lipid lowering drugs. In the Primary Prevention Study it was found during a 16 years' follow-up that the coronary heart disease risk was related to entry level of serum cholesterol both among those who had signs of coronary heart disease or angina pectoris, as well as among those with no such previous coronary heart disease events at entry. For each cholesterol level, the risk was about seven times higher among those who had had a myocardial infarction compared to those without any coronary heart disease event at entry. In those with angina the risk was about three to four times higher. An example shows how important it is to take the so-called 'regression dilution bias' into account, which results in steeper risk factor-incidence curves. The concept of 'population attributable risk' is also discussed. It is a general finding that the many with moderate elevations of risk factors contribute to most disease events. This is true for smoking, serum cholesterol, blood pressure etc. Results from various prospective studies have repeatedly demonstrated three main risk factors for coronary heart disease: cholesterol, high blood pressure and smoking, and they explain more than 90% of infarct cases in the middle-aged population. Other risk factors, including psychological, are, however, also of some importance and they are discussed briefly. The Goteborg population studies started in 1963. The data to 1990 show that among men there has been a decline in serum cholesterol and blood pressure, which has resulted in a decline in risk for coronary heart disease of 37%, well compatible with the registered decline of 30-40% in coronary heart disease incidence among men aged 45-54 years. Simultaneously, there has been a marked decline, especially among men, of 28-day fatality among hospitalized patients, but because most deaths occur outside hospital the decline in incidence has had greater importance for overall coronary heart disease mortality. Several studies have demonstrated the importance of stopping smoking, at least after myocardial infarction. Other interventions after a myocardial infarction are also important for the outcome, which has improved considerably over the last 20 years. In the general population in whom there is no sign of coronary heart disease, it is important to reduce risk factors among the many with moderate risk, by stopping smoking and changing diet.

Publication Types:

Lectures

: Acta Med Scand Suppl. 1988;728:150-8.

Related Articles, Links

Factors influencing total cholesterol and high-density lipoprotein cholesterol concentrations in a population at high coronary risk.

Patterson CC, McCrum E, McMaster D, Kerr M, Sykes D, Evans AE.

Belfast MONICA Project, Department of Community Medicine & Medical Statistics, Queen's University of Belfast Northern Ireland.

Serum total cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 1122 men and 1147 women aged between 25 and 64 years during the first Belfast MONICA survey, and the results subjected to multiple regression analysis. In both men and women, total cholesterol increased with age. Although HDL-cholesterol showed little variation with age, the values were considerably higher in women than men. Total cholesterol increased with body mass index while HDL-cholesterol decreased, and these findings persisted after adjustment for age. Regular exercise was associated with higher HDL-cholesterol values, even after adjustment for age and body mass index. Among men and women who abstained from alcohol, lower values of HDL-cholesterol were observed. In both sexes, cigarette smoking was associated with significant increases in total cholesterol values and decreases in HDL-cholesterol values, though some of these findings became apparent only after adjustment for other relevant factors. Perhaps surprisingly, a measure of health knowledge showed no association with blood lipid concentrations.

PMID: 3202024 [PubMed - indexed for MEDLINE]

Chronobiol Int. 2001 May;18(3):541-57.

Related Articles, Links

Influence of dietary intake and physical activity on annual rhythm of human blood cholesterol concentrations.

Bluher M, Hentschel B, Rassoul F, Richter V.

III. Medical Department, Faculty of Medicine, University of Leipzig, Germany. bluma@medizin.uni-leipzig.de

Seasonal variation in the plasma total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) have been repeatedly reported, with contradictory results regarding the pattern of seasonal variation of these parameters. Furthermore, it is still not well established whether the variation is due to changes in the nutrition or changes in physical activity depending on the season. The aim of this study was therefore to determine plasma TC and HDL-C in different groups of healthy participants: 19 vegetarians with a constant diet independent of the season, 14 athletes with almost constant physical activity over the year, and 114 controls in the age groups 20-26 years (mean age 24 + 1.5 years) and 40-48 years (mean age 44.3 + 2.1 years). Over 2 years, blood samples were collected every 2-3 months and were analyzed for plasma TC and HDL-C. At all visits, body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and nutrition and physical activity profiles were obtained. The seasonal model was calculated using object-oriented software for the analysis of longitudinal data in S (OSWALD); multiple regression analysis was used to determine the influence of age, gender, diet, and physical activity on seasonal changes of the lipid parameters. In all groups, we found an annual rhythm of the plasma TC and HDL-C concentrations, which can be mathematically described by a sine curve with a maximum in winter and a minimum in summer. This rhythm was independent of the age, gender, BMI, diet, or physical activity. The observed seasonal differences between the maximum and the minimum were about 5%-10% for TC and about 5%-8% for HDL-C concentration. These differences were greater than the determined circadian (TC 3.5%, HDL-C 4%) and day-to-day changes for TC and HDL-C (coefficient of variation <5% for both). In conclusion, annual rhythm of TC and HDL-C is not primarily induced by seasonal differences in dietary intake or physical activity. Therefore, the annual rhythm in cholesterol levels is most likely determined by endogenous factors or factors directly related to seasonal changes in the environment.

PMID: 11475422 [PubMed - indexed for MEDLINE]

Am J Cardiol. 2000 Apr 15;85(8):969-72.

Related Articles, Links

Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women.

Barnard ND, Scialli AR, Bertron P, Hurlock D, Edmonds K, Talev L.

Physicians Committee for Responsible Medicine, Washington DC, USA. nbarnard@pcrm.org

Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 10760336 [PubMed - indexed for MEDLINE]

Am J Clin Nutr. 1999 Sep;70(3 Suppl):525S-531S.

Related Articles, Links

The Oxford Vegetarian Study: an overview.

Appleby PN, Thorogood M, Mann JI, Key TJ.

Imperial Cancer Research Fund, Cancer Epidemiology Unit, Radcliffe Infirmary, Oxford, United Kingdom. appleby@icrf.icnet.uk

The Oxford Vegetarian Study is a prospective study of 6000 vegetarians and 5000 nonvegetarian control subjects recruited in the United Kingdom between 1980 and 1984. Cross-sectional analyses of study data showed that vegans had lower total- and LDL-cholesterol concentrations than did meat eaters; vegetarians and fish eaters had intermediate and similar values. Meat and cheese consumption were positively associated, and dietary fiber intake was inversely associated, with total-cholesterol concentration in both men and women. After 12 y of follow-up, all-cause mortality in the whole cohort was roughly half that in the population of England and Wales (standardized mortality ratio, 0.46; 95% CI, 0.42, 0.51). After adjusting for smoking, body mass index, and social class, death rates were lower in non-meat-eaters than in meat eaters for each of the mortality endpoints studied [relative risks and 95% CIs: 0.80 (0. 65, 0.99) for all causes of death, 0.72 (0.47, 1.10) for ischemic heart disease, and 0.61 (0.44, 0.84) for all malignant neoplasms]. Mortality from ischemic heart disease was also positively associated with estimated intakes of total animal fat, saturated animal fat, and dietary cholesterol. Other analyses showed that non-meat-eaters had only half the risk of meat eaters of requiring an emergency appendectomy, and that vegans in Britain may be at risk for iodine deficiency. Thus, the health of vegetarians in this study is generally good and compares favorably with that of the nonvegetarian control subjects. Larger studies are needed to examine rates of specific cancers and other diseases among vegetarians.

Br Med J (Clin Res Ed). 1987 Aug 8;295(6594):351-3.

Related Articles, Links

Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain.

Thorogood M, Carter R, Benfield L, McPherson K, Mann JI.

Department of Community Medicine and General Practice, Radcliffe Infirmary, Oxford.

Concentrations of total cholesterol and cholesterol in the various lipoprotein fractions were measured in vegans, vegetarians, fish eaters (who did not eat meat), and meat eaters. Total and low density lipoprotein cholesterol concentrations were higher in meat eaters than vegans, with vegetarians and fish eaters having intermediate and similar values. High density lipoprotein cholesterol concentration was highest in the fish eaters but did not differ among the other groups. There were striking trends with age in total and low density lipoprotein cholesterol concentrations, which differed between men and women: women showed a steady increase in concentration with age, whereas concentrations in men did not increase appreciably after the age of 40, which may partly explain sex differences in the prevalence of coronary heart disease. The differences in total cholesterol concentration suggest that the incidence of coronary heart disease may be 24% lower in lifelong British vegetarians and 57% lower in lifelong vegans than in meat eaters.

nn N Y Acad Sci. 2001 Apr;928:305-15.

Related Articles, Links

Caloric restriction in primates and relevance to humans.

Roth GS, Ingram DK, Lane MA.

Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. geor@vax.grc.nia.nih.gov

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a long-term longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake.

Publication Types:

Review

Review, Tutorial

PMID: 11795522 [PubMed - indexed for MEDLINE]

Am J Clin Nutr. 2003 Sep;78(3):361-9.

Related Articles, Links

Calorie restriction and aging: review of the literature and implications for studies in humans.

Heilbronn LK, Ravussin E.

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

Calorie restriction (CR) extends life span and retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism or mechanisms through which this occurs are unclear. CR reduces metabolic rate and oxidative stress, improves insulin sensitivity, and alters neuroendocrine and sympathetic nervous system function in animals. Whether prolonged CR increases life span (or improves biomarkers of aging) in humans is unknown. In experiments of nature, humans have been subjected to periods of nonvolitional partial starvation. However, the diets in almost all of these cases have been of poor quality. The absence of adequate information on the effects of good-quality, calorie-restricted diets in nonobese humans reflects the difficulties involved in conducting long-term studies in an environment so conducive to overfeeding. Such studies in free-living persons also raise ethical and methodologic issues. Future studies in nonobese humans should focus on the effects of prolonged CR on metabolic rate, on neuroendocrine adaptations, on diverse biomarkers of aging, and on predictors of chronic age-related diseases.

Publication Types:

Review

Review, Tutorial

PMID: 12936916 [PubMed - indexed for MEDLINE]

Science. 2003 Feb 28;299(5611):1346-51.

Related Articles, Links

The endocrine regulation of aging by insulin-like signals.

Tatar M, Bartke A, Antebi A.

Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA.

Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism.

Publication Types:

Review

Review, Tutorial

PMID: 12610294 [PubMed - indexed for MEDLINE]

: Cerebrovasc Dis. 2004;17 Suppl 1:81-8.

Related Articles, Links

Statins and stroke prevention.

Amarenco P, Lavallee P, Touboul PJ.

Department of Neurology and Stroke Center, Bichat-Claude-Bernard University Hospital and Medical School, Denis-Diderot University-Paris VII, Paris, France. amarenco@ccr.jussieu.fr

Four randomized trials with a statin and one trial with a fibrate showed a modest but significant absolute reduction in the incidence of stroke in patients with a previous myocardial infarction. The reasons for the positive effect of statins on stroke end-point are unclear since, paradoxically, the link between serum cholesterol level and stroke has never been fully established. Furthermore, the positive results of statins trials were mainly obtained in patients with an average or a low serum cholesterol level. This suggests nonhypolipidemic effects of these drugs, so-called pleiotropic effects, acting on the biologic promoters of plaque instability. Statins have a good overall safety profile with no increase of hemorrhagic stroke and no increase in cancer. They have positive effects in primary prevention of cardiovascular disease in high-risk young as well as elderly populations. Statins reduced stroke incidence in high-risk (mainly CHD, diabetics and hypertensives) population even with a normal baseline blood cholesterol level, which argues for a global cardiovascular risk-based treatment strategy. In patients with prior strokes, statins likely reduce the incidence of cononary events, but it is not yet proven that statins actually reduce the incidence of recurrent strokes in secondary prevention. If current hypotheses are verified by ongoing trials, we may expect between 20 to 30 more stroke events avoided per 1,000 patients treated during 2 years with a lipid-lowering agent, which adds to the 28 stroke events prevented with an antiplatelet agent over the same time period. This would be one of the most significant advances in stroke and vascular dementia prevention since the era of aspirin therapy. Copyright 2004 S. Karger AG, Basel

PMID: 14694285 [PubMed - in process]

Demnächst Lipidsenkung mit Rosuvastatin

More Power to Lower

DAVOS - "Je niedriger das Cholesterin, desto niedriger die Mortalität", erinnerte Professor Dr. Martin J. Kendall, University of Birmingham. In den grossen Lipidstudien 4S, CARE, LIPID und HPS konnte das Cholesterin zwischen 25 und 35 % gesenkt werden, was als extrem gut galt. Derzeit ist Atorvastatin das stärkste Statin, das, hochdosiert mit 80 mg, in der GREACE-Studie das LDL-Cholesterin um 46 % senken konnte. "Das ist exzellent", so der Experte. "Die Frage ist nur: Können wir es nicht besser machen?" Und er gab auch sogleich die Antwort: Mit Rosuvastatin* steht bald das stärkste Statin, das zudem niedrig dosiert wird, zur Verfügung.

Int J Clin Pract. 2002 Jan-Feb;56(1):53-6.

Related Articles, Links

The MRC/BHF Heart Protection Study: preliminary results.

Collins R, Peto R, Armitage J.

Oxford Clinical Trials Service Unit.

The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial of statin therapy ever conducted. It provides important and definitive new information on women, the elderly, diabetics, and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease. It is a prospective double blind randomised controlled trial with a 2 x 2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS specifically included patients with high risk for coronary heart disease (CHD) but characteristics that excluded them from participation in previous statin trials. Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated. Results show a 12% reduction in total mortality, a 17% reduction in vascular mortality, a 24% reduction in CHD events, a 27% reduction in all strokes and a 16% reduction in non-coronary revascularisations. Among high-risk patients in this western population (with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit; even among those with pre-treatment cholesterol levels below current national recommended targets. Over the 5.5 year study period patients and their doctors were encouraged to add an active non-study statin to the study regimen if they wished to do so. Thus the trial eventually had only two-thirds complying with the original intention-to-treat design. Nevertheless, results were highly significant for the study statin--simvastatin 40 mg once daily. Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 11831837 [PubMed - indexed for MEDLINE]

MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.

Heart Protection Study Collaborative Group.

BACKGROUND: It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. METHODS: 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. FINDINGS: There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. INTERPRETATION: Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.

Publication Types:

Clinical Trial

Multicenter Study

Randomized Controlled Trial

PMID: 12114037 [PubMed - indexed for MEDLINE]

Cholesterinwerte verändern sich im Rhythmus der Jahreszeiten

Hoher Blutfettspiegel im Winter

von Sonja Kastilan

Menschen sind ein bisschen wie Wetterkarten. Auf Regen folgt Sonnenschein, Hochs und Tiefs wechseln sich ab, und abgesehen von der Stimmung unterliegt auch der Blutdruck - innerhalb bestimmter Grenzen - einem stetigen Wandel. Seine Werte können tagesbedingt stark schwanken, was gerade bei jüngeren Menschen häufig zu der Fehldiagnose "Bluthochdruck" führt.

So warnen Mediziner der Universität Birmingham in der Fachzeitschrift "British Medical Journal" davor, bei unter 35-Jährigen eine oft lebenslang andauernde Therapie zu beginnen auf Basis sporadischer Blutdruckmessungen. Für ihre Studie hatten die Forscher untersucht, wie oft Bluthochdruck bei Menschen unter 35 Jahren diagnostiziert wird, und berechneten, bei wie vielen davon der Blutdruck tatsächlich zu hoch ist: Meist war die Diagnose falsch.

Um zu vermeiden, dass Gesunde unnötig zu Bluthochdruckpatienten erklärt werden und gar Tabletten einnehmen, raten die britischen Mediziner, die Diagnose entweder erst nach mehreren Messungen zu stellen oder aber den entsprechenden Grenzwert höher anzusetzen. Aber damit nicht genug an Auf und Ab: Den Wechsel der Jahreszeiten sollten Mediziner ebenfalls berücksichtigen. Zumindest wenn sie die Cholesterinwerte ihrer Patienten beurteilen. US-Forscher stellen in "The Archives of Internal Medicine" fest, dass im Herbst der Anteil der Fette im Blut zunimmt und den höchsten Level in den Wintermonaten erreicht. Bei Frauen war dies besonders deutlich, sie hatten die höchsten Werte im Januar - etwa 5,4 Milligramm Cholesterin mehr pro Deziliter Blut. Ähnlich reagierten auch Menschen mit bereits höherem Cholesterinspiegel.

Die Forscher von der University of Massachusetts in Worcester hatten für ihre Studie Daten von mehr als 500 Freiwilligen untersucht: Ernährung, Sport, Licht und Cholesterinwerte. Als Ursache für die steigenden Blutfettspiegel im Winter vermuten sie vor allem Änderungen des Plasmavolumens - beeinflusst durch Temperaturunterschiede und Bewegungsmangel. Die Schwankungen im Rhythmus der Jahrszeiten könnten dafür verantwortlich sein, dass einige im Winter die Diagnose "zu hohe Cholesterinwerte" hören. Sport kann nicht schaden, aber vielleicht sollte die Messung wiederholt werden: Tiefstwerte herrschen im Sommer, dann ist vor allem die Stimmung hoch.

Artikel erschienen am 27. April 2004

© WELT.de 1995 - 2004