Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Triglyceride-Mediated Pathways and Coronary Disease: Collaborative Analysis of 101 Studies
Topic: Prevention/Vascular
Date Posted: 5/11/2010
Author(s): Sarwar N, Sandhu MS, Ricketts SL, et al., on behalf of the Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration.
Citation: Lancet 2010;375:1634-1639.
Clinical Trial: No
Study Question: Are triglyceride-mediated pathways causally relevant to coronary heart disease (CHD)?
Methods: The study assessed the –1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of CHD. The disease risk was assessed for genetically-raised triglyceride concentration (20,842 patients with CHD and 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302,430 participants with no history of cardiovascular disease; 12,785 incident cases of CHD during 2.79 million person-years at risk). The authors also analyzed –1131T>C in 1,795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy.
Results: The minor allele frequency of –1131T>C was 8% (95% confidence interval, 7-9). –1131T>C was not significantly associated with several nonlipid risk factors or low-density lipoprotein (LDL) cholesterol; however, it was significantly but modestly associated with lower high-density lipoprotein cholesterol (HDL-C) (mean difference per C allele, 3.5%; lower apolipoprotein A-I [1.3%; 0.023 g/L]; and higher apolipoprotein B [3.2%; 0.027 g/L]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% or 0.25 mmol/L, higher (p = 4.4 Ч 10–24). The odds ratio for CHD was 1.18 (p = 2.6 Ч 10–7) per C allele, which was concordant with the hazard ratio of 1.10 per 16% higher triglyceride concentration recorded in prospective studies. –1131T>C was significantly associated with higher very LDL (VLDL) particle concentration (mean difference per C allele, 12.2 nmol/L; p = 9.3 Ч 10–8) and smaller HDL particle size (0.14 nmol; p = 7.0 Ч 10–5), factors that could mediate the effects of triglyceride.
Conclusions: The authors concluded that these data are consistent with a causal association between triglyceride-mediated pathways and CHD.
Perspective: The mechanisms considered for triglycerides increasing risk for CHD and CV events are thought to be the increase in VLDL triglyceride-rich remnant particles, small highly atherogenic LDL particles, less efficient small dense HDL particles, and prothrombosis. The finding that a genetic determinant of triglyceride levels appears to increase risk independent of other known risk factors including diabetes further supports the rationale for considering targeting triglycerides. Future drug trials should consider the impact of the –1131T>C (rs662799) promoter polymorphism of the APOA5 gene, which appears to impact the effect of both statins and fibrates. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Association of Temporal Trends in Risk Factors and Treatment Uptake With Coronary Heart Disease Mortality, 1994-2005
Topic: Prevention/Vascular
Date Posted: 5/11/2010 4:00:00 PM
Author(s): Wijeysundera HC, Machado M, Farahati F, et al.
Citation: JAMA 2010;303:1841-1847.
Clinical Trial: No
Study Question: Are trends in coronary heart disease (CHD) risk factors and management associated with mortality?
Methods: This was a prospective analytic study of the general population (age 25-84 years) residing in Ontario, Canada between 1994 and 2005, using the IMPACT model (which integrates data on population size, CHD mortality, risk factors, and treatment uptake). The association between CHD mortality and risk factors for eight separate CHD populations, and population trends in six risk factors was quantified using relative risks and regression coefficients from published literature. The main outcome of interest was number of deaths prevented or delayed in 2005. Secondary outcomes included improvements in medical treatments and trends in risk factors.
Results: Age-adjusted CHD mortality decreased by 35%, from 191 to 125 deaths per 100,000 inhabitants over the time period examined (1994-2005). This translated into an estimated 7,585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range 11-124%) of the total mortality decrease, most notably for acute myocardial infarction (8%, range -5% to 40%), chronic stable coronary artery disease (17%, range 7-35%), and heart failure occurring while in the community (10%, range 6-31%). Trends in risk factors accounted for 48% (range 28-64%) prevented or delayed CHD deaths or 3,660 fewer deaths. Improvements in total cholesterol and systolic blood pressure accounted for much of this mortality reduction. Increases in diabetes and body mass index (BMI) were associated with higher CHD mortality (6%, range 4-8% for diabetes and 2%, range 1-4% for BMI).
Conclusions: The authors concluded that decreases in CHD mortality observed between 1994 and 2005 were associated primarily with improvements in CHD risk factors, but also with improvements in medical management of heart disease.
Perspective: These findings support the continued primary and secondary prevention efforts to improve traditional risk factors in our population. This together with continued advancement in the treatment of CHD will likely assist in the continued reduction of CHD mortality rates. However, the epidemic of obesity and associated medical problems such as diabetes will retard progress in reducing mortality and morbidity related to CHD. Elizabeth A. Jackson, M.D., F.A.C.C.