Does the impact of smoking on coronary heart disease differ by low-density lipoprotein cholesterol level? - The Atherosclerosis Risk in Communities (ARIC) Study

Background: The association of smoking with coronary heart disease (CHD) occurrence has been reported to be weaker for populations with lower plasma cholesterol levels. Recent studies suggest that low-density lipoprotein cholesterol (LDL-C) and smoking contribute to different stages of atherosclerosis, so the present study was designed to test the hypothersis that smoking is a stronger risk factor for CHD when LDL-C is high. Methods and Results: The study group of 13,410 middle-aged adults who were initially free of stroke and CHD were followed and over 13.3 years there were 932 incident CHD events. Tests for multiplicative interaction were performed using proportional hazards models. Both smoking and increased LDL-C were risk factors for CHD incidence. The relative hazard (RH) of CHD in relation to smoking tended to be larger among higher LDL-C categories compared with lower LDL-C categories. For example, when the participants were dichotomized into 4 categories, using smoking ≥15 cigarettes per day and LDL-C ≥130 mg/dl as cutoffs, those with high LDL-C and heavier cigarette smoking showed a very high RH of CHD (RH=2.81) compared with that expected from the product of the RHs of high LDL-C (RH=1.15) onlyxheavy smoking only (RH=1.71) (p for interaction=0.04). Conclusions: These results suggest positive multiplicative interactions between smoking and LDL-C for CHD incidence.