Heart rate variability and progression of coronary atherosclerosis

Low heart rate (HR) variability is associated with increased risk of cardio vascular morbidity and mortality, but the causes and mechanisms of this ass ociation are not well known. This prospective study was designed to test th e hypothesis that reduced HR variability is related to progression of coron ary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a m ulticenter study to evaluate the angiographic progression of coronary arter y disease in patients with prior coronary artery bypass surgery and low hig h-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participant s were randomized to receive a placebo or gemfibrozil therapy. The progress ion of coronary atherosclerosis was estimated by quantitative, computer-ass isted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The prog ression of focal coronary atherosclerosis of the patients randomized to pla cebo therapy was more marked in the tertile with the lowest standard deviat ion of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interv al [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; m ean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0.04 to 0.02 mm) (P<0.001 betwe en the tertiles). This association was abolished by gemfibrozil. SDNN was l ower (P<0.001) and minimum HR was faster (P<0.01) in the patients with mark ed progression than in those with regression of focal coronary atherosclero sis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary at herosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001) . Low HR variability analyzed from ambulatory ECG predicts rapid progressio n of coronary artery disease. HR variability provided information on progre ssion of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.