Disentangling the inverse LDL-C-hemorrhagic stroke association in Chinese adults with hypertension: findings from the Chinese Multi-provincial Cohort Study.

Why lower low-density lipoprotein cholesterol (LDL-C) was associated with a decreased atherosclerotic cardiovascular disease (ASCVD) risk but an increased hemorrhagic stroke (HS) risk in hypertensive adults remains unclear. We examined whether the inverse LDL-C-HS association partly arises from its effect on ASCVD. We estimated separable effects of LDL-C on HS outside (ie, separable direct effect) or only through its effect on ASCVD (ie, separable indirect effect) in hypertensive adults from the Chinese Multiprovincial Cohort Study. We quantified such effects using numbers needed to treat (NNT) to prevent or cause an extra HS based on the restricted mean event-free time until a 25-year follow-up. Low-density lipoprotein cholesterol <70 mg/dL was not associated with an increased HS risk compared to LDL-C $\ge$70 mg/dL regarding total and separable direct effects. However, a small separable indirect effect (ie, NNT to harm: 9722 participants) was noted and validated via a series of sensitivity analyses. Moreover, modified effects were observed, particularly among patients 35-49 years, men, and those with SBP $\ge$140 mm Hg. These results suggest the inverse LDL-C-HS association in hypertensive adults is partly due to its effect on ASCVD. A better understanding of such associations would provide more enlightening into stroke prevention.