M. H. Frick

The Helsinki Heart Study: an 8.5-year safety and mortality follow-up

Abstract. Objectives. Earlier monitoring of all symptoms, hospital admissions, cancer diagnoses and causes of death during gemfibrozil treatment had raised some suspicions which called for further follow‐up.

Leukocytes as a coronary risk factor in a dyslipidemic male population

The role of an elevated serum leukocyte count (WBC) as a coronary risk factor was investigated using a nested case-control design in dyslipidemic middle-aged men (n = 420) participating in the Helsinki Heart Study, a coronary primary prevention trial. Baseline WBC was significantly higher, 6.93 (2.11) x 10(9)/L in subjects with cardiac events, than in controls, 6.26 (1.88) x 10(9)/L; p less than 0.002. This association was time-dependent, however, since the difference was not significant for events occurring during the second half of the 5-year study. Using nonsmokers in the lowest WBC tertile as the reference sample, the relative risks in the highest WBC tertile were 1.86 (95% confidence intervals [CI] 0.81 to 4.28) for nonsmokers and 3.07 (95% CI 2.23 to 8.19) for smokers. Logistic regression analysis including smoking in the model disclosed an independent contribution of elevated WBC to coronary heart disease. We conclude that elevated leukocyte count was a coronary risk factor even in this dyslipidemic population.

Seasonal variation in high density lipoprotein cholesterol

We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol > or = 5.2 mmol/l) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 +/- 0.265 mmol/l) compared with a stable level (5-year mean 1.248 +/- 0.281 mmol/l) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence.

Antihypertensive Therapy in Dyslipidemic Men: Effects on Coronary Heart Disease Incidence and Total Mortality

To investigate the influence of antihypertensive therapy and the success of blood pressure control on coronary heart disease incidence and total mortality, we studied dyslipidemic middle-aged men participating in the placebo arm of the Helsinki Heart Study, a randomized coronary primary prevention trial with gemfibrozil. Based on blood pressure level and the presence of antihypertensive therapy at study entry, the participants were classified into four categories. Relative risks of coronary heart disease (nonfatal myocardial infarction or cardiac death) and total mortality during the 5-year trial period were calculated using Cox proportional hazards models. With subjects who were not using antihypertensive drugs and who had normal blood pressure (category I) as reference, the relative risks of coronary heart disease during the trial period were 2.1 (95% confidence interval [CI], 1.3 to 3.3) in untreated hypertensive subjects (category II), 0.9 (95% CI, 0.2 to 3.8) in subjects with successful antihypertensive therapy (category III), and 2.0 (95% CI, 1.0 to 4.1) in subjects who remained hypertensive despite drug therapy (category IV). The relative risks of death were 1.9 (95% CI, 0.9 to 3.9) in category II and 1.0 (95% CI, 0.1 to 7.3) in category III; in category IV subjects, those with unsuccessful antihypertensive therapy, the relative risk was 4.4 (95% CI, 2.0 to 9.6). The excess mortality in this category was due to cardiovascular causes and was clustered in subjects with multiple drug therapy for hypertension control. We conclude that successful antihypertensive therapy in dyslipidemic men reduced coronary heart disease incidence despite its adverse effects on high-density lipoprotein cholesterol and triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)