Marek H. Dominiczak

Meta-analysis and causality: what about evidence-based biochemistry?

In 2009, The Emerging Risk Factor Collaboration (ERFC) published a paper based on the meta-analysis of 68 studies of people without history of coronary heart disease (CHD) [1 ]. In this study, plasma triglycerides were shown to be related to CHD risk with a hazard ratio of 1.37 [95% confidence interval (CI) 1.31–1.42] per 1 SD change in plasma concentration. However, after adjustment for nonlipid risk factors [age, sex, systolic blood pressure (SBP), smoking diabetes and BMI] and for nonhigh-density cholesterol (non-HDL-C) and high-density cholesterol (HDL-C), the hazard ratio was attenuated to 0.99, suggesting no independent association of triglyceride concentration with CHD risk. The conclusion then was that, as far as population-wide assessment of cardiovascular risk is concerned, ‘lipid assessment in vascular disease can be simplified by measurement of either cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride’.

Hyperlipidaemia and cardiovascular disease: apolipoprotein measurements and metabolic syndrome as predictors of cardiovascular risk.

Apolipoproteins predict cardiovascular risk better than conventional lipid measurements Whether apolipoproteins are the best parameters to assess the risk of cardiovascular disease (CVD) is not a new question. Substantial data suggest that they are superior to conventional lipid analyses. However, current risk assessment procedures and guidelines, as well as the majority of clinical studies underpinning cardiovascular prevention, have been based on conventional lipid analyses: total cholesterol, LDL-cholesterol, HDLcholesterol and triglycerides. The recent data from the INTERHEART study [1 ] suggest again that the apolipoprotein (Apo) B/A-I ratio predicts acute myocardial infarction (MI) better than traditional lipid parameters.

Hyperlipidaemia and cardiovascular disease: nonfasting triglycerides gain momentum--but nothing changes on the metabolic syndrome front.

A clear association was observed between nonfasting triglyceride concentration, the incidence of myocardial infarction, ischaemic heart disease and total mortality, with odds ratio for data adjusted for age and HDL cholesterol being in the range of 1.3–3.3. After a multifactorial adjustment the odds ratios were 1.4–5.3 for myocardial infarction, and 1.4–2.6 for coronary heart disease (CHD) in women and 1.1–1.5 for CHD in men. The study is complemented by an elegant demonstration, in a sample of over 5000 individuals from a different cohort, of a relationship between nonfasting triglycerides and the concentration of remnant lipoproteins. Generation of the atherogenic remnants in postprandial state is the lynchpin of the hypothesis that atherosclerosis is a postprandial phenomenon. Postprandial increase in plasma triglycerides is more protracted than an increase in glucose concentration: hypertriglyceridaemia takes 10 h to return to baseline, the curve being rather flat with a peak concentration 4 h after a meal.

A matter of judgement: clinical guidelines and scientific reductionism

The European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) I, II and III surveys were conducted in 1995, 1999–2000 and 2006–2007, respectively [1 ]. Their aim was to gain insight into the status of preventive cardiology practice. In the current study, the surveys conducted in eight European countries were compared. The participants were men and women 70 years or younger (mean age 60 years) who underwent coronary artery bypass graft (CABG), percutaneous transluminal coronary intervention (PCI) or were admitted with myocardial infarction (MI) or unstable angina. The participants were interviewed and their risk factors and treatment were assessed between 1 and 1.5 years after the index event: 3180, 2975 and 2392 patients were seen in EUROASPIRE I, II and III, respectively. Results show that the prevalence of smoking was similar across the three surveys but in EUROASPIRE III there were more women smokers below 50 years of age. Obesity steadily increasedfrom 25%inEUROASPIRE I to 38% in EUROASPIRE III. The prevalence of hypertension was similar across the three surveys, whereas raised cholesterol (above 4.5 mmol/l) became less frequent (prevalence 94.5% in EUROASPIRE I and 46.2% in EUROASPIRE III).Self-reporteddiabetes increased from 17.4 to 28%. Interestingly, the proportion of blood pressure values remaining below target has remained virtually unchanged between EUROASPIRE I and EUROASPIRE III, staying below 50%. On the contrary, the prevalence of hypercholesterolaemia very much decreased.

Hyperlipidaemia and cardiovascular disease - Back to basics: dietary patterns, foods and cardiovascular risk

Diet and other lifestyle measures remain the mainstay of cardiovascular prevention. They gain even more importance in the face of current obesity epidemics. Yet dietary recommendations are often confusing, and could be contradictory in different medical specialties. Dietary patterns are important, and yet recommendations often focus on particular nutrients in a way not directly translatable into practical measures. Changing the diet is never an issue of simple avoidance of a particular nutrient; it is about changing the pattern. Here, recent articles address the effects of the Mediterranean dietary pattern, and that of coffee and particular kinds of tea on cardiovascular diseases (CVD).

Hyperlipidaemia and cardiovascular disease: nonlipid-lowering effects of omega-3 fatty acids, statins and fibrates.

Here, as part of the randomized, placebo-controlled GISSI-heart failure (GISSI-HF) study [1 ], n-3 PUFAs were given to patients with New York Heart Association (NYHA) class II–IV heart failure. Most patients had left ventricular ejection fraction below 40%; 3494 participants were treated with n-3 PUFA in addition to the standard treatment of heart failure, and 3481 received placebo. The median follow-up time was 3.9 years. The average age of participants was 67 years, and 22% were women. Approximately 70% of the participants were also involved in the rosuvastatin study addressed below.

Hyperlipidaemia and cardiovascular disease: ALLHAT, low-fat diet and apolipoprotein measurements: are there emerging issues?

The aim of ALLHAT-LLT, the Lipid-Lowering Trial (LLT) of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), was to compare treatment with 40 mg of pravastatin (n = 5170) with a ‘usual-care’ group (n = 5185) [1]. Mean age of participants was 66 years, 49% were women, 38% were black and 23% Hispanic; 14% had a history of coronary heart disease (CHD) and 35% had diabetes. Baseline low-density lipoprotein (LDL) cholesterol was 120–189 mg/dl (3.1–4.89 mM) and 100–129 mg/dl (2.59– 3.34 mM) in those with CHD, and serum triglyceride concentration was below 350 mg/dl (4.0 mM). Mean follow up time was 4.8 years. During the trial, 30% of participants in the usual-care group commenced statin treatment and this, not unexpectedly, affected the final difference in cholesterol levels between the two groups. In the final analysis serum cholesterol was reduced by 17% in the pravastatin group and by just 8% in the usualcare group; LDL cholesterol was reduced by 28 and 11%, respectively. The overall total mortality was 12.3%, which was close to the original predictions. Disappointingly however, the principal endpoint, the all-cause mortality, did not differ between the pravastatin and the usual-care group. The number of cardiovascular deaths was also similar in the two groups, as were the rates of stroke and heart failure. Although the number of CHD events was lower in the pravastatin group (380 compared with 421) this was not statistically significant (P = 0.16).