Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality.

Abstract-Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (Ͻ1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals ( Key Words: coronary artery disease Ⅲ lipids Ⅲ heart period Ⅲ angiography E levated heart rate (HR) and reduced HR variability are associated with an increased risk of cardiovascular morbidity and mortality in various populations, 1-8 but the pathophysiological link between these associations is not well understood. Experimental studies on monkeys fed an atherogenic diet have demonstrated a relationship between resting HR and progression of coronary atherosclerosis, 9 -11 and there is also a strong relationship between HR and arterial stiffness, 12 but there has been little evidence of any association between HR, or its variability, and human coronary atherosclerosis.Progression of coronary artery stenoses in repeated coronary angiograms increases the risk of adverse cardiac events, suggesting that rapid progression predisposes patients to acute complications of coronary artery plaques and serves as a surrogate end point for clinical events. 13,14 Lipid-modifying therapy has been shown to prevent the progression of coronary atherosclerosis, confirming that abnormalities in plasma lipid concentrations are strongly associated with the progression of coronary artery disease and the occurrence of adverse clinical events. 14 However, lipid theory may not explain all aspects of coronary artery disease, eg, the rapid progression of discrete stenoses in specific coronary arterial regions, which is thought to result from an interplay of hemodynamic, metabolic, and hemostatic factors. [15][16][17][18] To test the hypothesis that elevated HR and reduced HR variability are associated with the progression of human coronary atherosclerosis in patients with lipid abnormalities, we studied HR and its variability, measured by ambulatory ECG, and the angiographic progression of coronary artery disease in patients with reduced HDL cholesterol concentrations.