Longitudinal effects of lipid indices on incident cardiovascular diseases adjusting for time-varying confounding using marginal structural models: 25 years follow-up of two US cohort studies

BACKGROUND: This study assesses the effect of blood lipid indices and lipid ratios on cardiovascular diseases (CVDs) using inverse probability-of-exposure weighted estimation of marginal structural models (MSMs). METHODS: A pooled dataset of two US representative cohort studies, including 16736 participants aged 42–84 years with complete information at baseline, was used. The effect of each lipid index, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C on coronary heart disease (CHD) and stroke were estimated using weighted Cox regression. RESULTS: There were 1638 cases of CHD and 1017 cases of stroke during a median follow-up of 17.1 years (interquartile range: 8.5 to 25.7). Compared to optimal levels, the risk of CVD outcomes increased substantially in high levels of TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C. If everyone had always had high levels of TC (≥240 mg/dL), risk of CHD would have been 2.15 times higher, and risk of stroke 1.35 times higher than if they had always had optimal levels (<200 mg/dL). Moreover, if all participants had been kept at very high (≥190 mg/dL) levels of LDL-C, risk of CHD would have been 2.62 times higher and risk of stroke would have been 1.92 times higher than if all participants had been kept at optimal levels, respectively. Our results suggest that high levels of HDL-C may be protective for CHD, but not for stroke. There was also no evidence of an adverse effect of high triglyceride levels on stroke. CONCLUSIONS: Using MSM, this study highlights the effect of TC and LDL-C on CVD, with a stronger effect on CHD than on stroke. There was no evidence for a protective effect of high levels of HDL-C on stroke. Besides, triglyceride was not found to affect stroke.