Remnant cholesterol and risk of hypertension: a prospective cohort study and meta-analysis

Abstract Background To date, few studies have reported a significant association between remnant cholesterol (RC) and hypertension. However, the vast majority of previous studies have not considered systolic and diastolic blood pressure (SBP and DBP) as covariates in their statistical analyses, which raises questions regarding the independent role of RC in the development of hypertension. Purpose We evaluated the association between RC and two decades risk of incident hypertension within the context of a prospective cohort study. Then, we combined them with previous results as part of a meta-analysis. Methods At baseline, 5,264 participants (3,312 women) with mean age of 39.1 years were recruited. Hypertension was defined as: SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or a history of anti-hypertensive medication prescription. Low-density lipoprotein cholesterol (LDL-C) was calculated according to the Martin-Hopkins method. RC was calculated as the difference between total cholesterol and the sum of high-density lipoprotein cholesterol (HDL-C) and LDL-C. Multivariable Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) with three models: model 1: age and sex adjusted; model 2: model 1 + smoking + marital + education + physical activity + cardiovascular diseases (CVD)+ diabetes + lipid-lowering medication + body mass index (BMI) + waist circumference + estimated glomerular filtration rate + triglyceride to HDL-C ratio; model 3: model 2 + SBP + DBP. We further examined this association, combining our results with results for reported from five other observational studies in a meta-analysis. Results During a median follow-up duration of 12.4 years, 2,189 events of hypertension occurred. In the continuous analysis, HRs (95%CIs) of incident hypertension per each 1-standard deviation increment of RC in model 1, 2 and 3 were calculated as 1.20 (1.16-1.23), 1.11 (1.06-1.15) and 1.00 (0.91-1.10), respectively. Similarly, in our categorical analysis, the HRs (95% CIs) for incident hypertension in the fourth quartile of RC compared to the first quartile were 2.01 (1.76-2.30) in Model 1, 1.28 (1.07-1.54) in Model 2, and 1.02 (0.85-1.22) in Model 3. Moreover, the results of the meta-analysis showed a significant and positive association between high compared to low RC levels and the risk of hypertension, with an effect size of 1.36 (95% CI: 1.18-1.56), although substantial heterogeneity was observed across studies (I² = 99.83%). Conclusion Our results indicated that although higher RC levels were associated with an increased risk of incident hypertension, this risk was not independent of SBP and DBP levels.