Hyperlipidemias: Stefanadis CI

Michaelides AP, Fourlas CA, Pitsavos C, Andrikopoulos GK, Skoumas I, Kartalis A, Katsaros A, Stougiannos P, Stefanadis CI. · Department of Cardiology Clinic, Medical School of Athens University, Athens, Greece. · Coron Artery Dis. · Pubmed #15585985 No free full text.

Abstract: OBJECTIVE: Familial hypercholesterolaemia (FH) is a frequent genetic disorder in Europe, affecting one in 500 people in its heterozygous form. Both homozygous and heterozygous forms are correlated with increased incidence of cardiovascular events. METHODS: We investigated clinical and biochemical parameters possibly associated with the results of exercise testing (ET) in asymptomatic patients with heterozygous FH. The study population was derived from outpatients of the Lipid Center in our department and consisted of 194 patients with heterozygous FH who had no medical history of coronary artery disease (CAD) or angina-like symptoms and who had agreed to undergo ET. RESULTS: Sex, body mass index, smoking status, diabetes mellitus, family history of CAD, presence of xanthomas and total cholesterol, triglyceride, low-density and high-density lipoprotein cholesterol, apolipoproteins A and B and lipoprotein (a) levels did not differ significantly between patients with positive and negative ET. Higher fibrinogen levels, arterial hypertension and family history of CAD were more frequent among patients with positive ET. However, in multivariate analysis adjusted for all the aforementioned variables, only high fibrinogen levels were significantly and independently associated with a positive result of ET. CONCLUSIONS: Lipid and coronary risk factor profiles do not seem to predict exercise-induced myocardial ischaemia in asymptomatic patients with heterozygous FH. However, in this high-risk population for cardiovascular events, fibrinogen levels are an independent predictor of positive ET. The adverse effects of FH on the cardiovascular system may be partly mediated by coagulability factors, whose role in the management of FH patients remains to be fully clarified.

Andrikopoulos GK, Richter DJ, Needham EW, Tzeis SE, Zairis MN, Gialafos EJ, Vogiatzi PG, Papasteriadis EG, Kardaras FG, Foussas SG, Gialafos JE, Stefanadis CI, Toutouzas PK, Mattu RK, Anonymous00361. · First Cardiac Department, Evangelismos Hospital, Athens, Greece. · Eur J Cardiovasc Prev Rehabil. · Pubmed #15580058 No free full text.

Abstract: BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). DESIGN AND METHODS: Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. RESULTS: In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.

Pitsavos CH, Chrysohoou C, Panagiotakos DB, Kokkinos P, Skoumas J, Papaioannou I, Michaelides AP, Singh S, Stefanadis CI. · First Cardiology Department, School of Medicine, University of Athens, Greece. · Atherosclerosis. · Pubmed #15064112 No free full text.

Abstract: BACKGROUND: Several clinical and observational studies have established that exercise capacity and activity status are strong predictors of cardiovascular and overall mortality. We aimed to evaluate the relationship between exercise tolerance test (ETT) indices and occurrence of coronary heart disease (CHD), in patients with heterozygous Familial Hypercholesterolemia (eFH). METHODS: During 1987-1997, we enrolled 639 cardiovascular disease-free patients with heterozygous eFH; 58 (9%) patients were excluded since they had a positive ETT. A fatal or non-fatal CHD event was the end point. Cox proportional hazards models were applied to evaluate the association between the investigated outcome and ETT indices. RESULTS: During the follow-up (1987-2002), 53 (18%) men and 34 (10%) women developed a CHD event (11 were fatal). The age-adjusted event rate was 87 events per 2915 person-years (3%). Statistical analysis revealed that exercise capacity (hazard ratio = 0.82, P < 0.001), heart rate recovery at 1 min (hazard ratio = 0.91, P < 0.05), and peak pulse pressure levels (hazard ratio = 1.03, P < 0.001), were predictors of CHD, after controlling for several potential confounders. CONCLUSION: Decreased exercise capacity, a delayed decrease in heart rate during the first minute of graded exercise, and increased peak pulse pressure are strong predictors of coronary events in patients with eFH. Physical activity should be strongly recommended in these patients.

Panagiotakos DB, Pitsavos C, Skoumas J, Chrysohoou C, Toutouza M, Stefanadis CI, Toutouzas PK. · Department of Cardiology, School of Medicine, University of Athens, Greece. · Curr Med Res Opin. · Pubmed #12755140 No free full text.

Abstract: This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p < 0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio = 2.45, p < 0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the postmenopausal status (hazard ratio = 0.26, p < 0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio = 1.17, p < 0.05); hypertension increased the risk for an adverse event (hazard ratio = 3.02, p < 0.05) and a 1 mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio = 1.04, p < 0.05). With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH.