Remnant cholesterol predicts progression from prehypertension to incident hypertension: Evidence from a prospective cohort study and Mendelian randomization analysis

ObjectiveRemnant cholesterol (RC), a marker of triglyceride-rich lipoprotein remnants, has emerged as an important contributor to residual cardiometabolic risk. However, whether RC contributes to the transition from prehypertension to clinical hypertension remains unclear. We investigated the association between RC and incident hypertension among adults with prehypertension and further assessed genetic evidence using Mendelian randomization (MR).MethodsThis prospective cohort study included 2,858 adults with prehypertension from the China Health and Retirement Longitudinal Study, followed from 2011 to 2015. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Multivariable logistic regression, restricted cubic spline analysis, subgroup analyses, and receiver operating characteristic analysis were performed. Two-sample MR, including inverse-variance weighted and Bayesian weighted MR methods, was used to evaluate the genetic association between RC and hypertension-related traits.ResultsDuring 4 years of follow-up, 891 participants developed incident hypertension. Higher RC was independently associated with increased odds of incident hypertension. In the fully adjusted model, each 1 mg/dL increase in RC was associated with a 2% higher odds of hypertension. Compared with participants in the lowest RC quartile, those in the highest quartile had 67% higher odds of incident hypertension, corresponding to an absolute increase of 11.86% in cumulative hypertension incidence during follow-up. Compared with the lowest RC quartile, the highest quartile showed a significantly higher risk of incident hypertension. Restricted cubic spline analysis demonstrated a linear dose-response association, with no evidence of nonlinearity. Subgroup analyses suggested stronger associations among older adults, non-smokers, individuals with normal body weight, and participants without depressive symptoms. MR analyses further supported a positive genetic association between elevated RC and hypertension-related traits.ConclusionsAmong adults with prehypertension, elevated RC was independently and linearly associated with higher risk of progression to incident hypertension. Genetic evidence further supported a potential role of RC in hypertension-related traits. These findings suggest that RC, which can be readily calculated from routine lipid profiles, may complement existing approaches for hypertension risk assessment and targeted blood pressure monitoring among individuals with prehypertension.