Abstract
Background: Individuals with abnormal serum lipid levels are at an augmented risk of atherosclerotic cardiovascular diseases (CVDs). The purpose of this study was to evaluate the significance of serum lipid concentrations as determinants for the risk of CVD and all-cause mortality (ACM).
Methods: This prospective cohort study involved individuals who were part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study initiated in 2007. A total of 9704 individuals aged 35- 65 years were involved in the current study. The participants were monitored for about a decade to track mortality and its underlying causes. Multivariable Cox proportional hazards models were applied to estimate hazard ratios (HRs) for serum levels of LDL-C, HDL-C, non-HDL-C, and triglycerides (TG), analyzed both as continuous variables and categorized into tertiles. Three models were developed: Model 1 (unadjusted), Model 2 (adjusted for age and sex), and Model 3 (further adjusted for BMI, smoking status, diabetes, hypertension, CVD, job, marital status, education level, and lipid-lowering drugs use). Kaplan–Meier survival analysis compared outcomes across lipid tertiles. Subgroup analyses were also performed to evaluate and control for confounding variables related to serum lipid levels and mortality.
Results: Over a follow-up period of 10 years, there were 429 (4.4%) deaths, including 185 cases due to CVD and 124 cases due to cancer. LDL-C, HDL-C, non-HDL cholesterol, and TG were categorized into three groups based on tertiles. Based on Cox model analysis, after full adjustment, individuals in the second (37.9–45.8 mg/dL) and third (45.8–96.2 mg/dL) tertiles of HDL-C had a significantly lower risk of ACM compared with the lowest tertile (≤37.9 mg/dL) (HR=0.72, 95% CI: 0.57–0.92; and HR=0.81, 95% CI: 0.64–1.03, respectively). Similarly, the risk of cardiovascular mortality was reduced in the second tertile (HR=0.66, 95% CI: 0.46–0.94). No significant associations were found between LDL-C and mortality after adjustment. Kaplan–Meier analyses confirmed significant survival differences across HDL-C (P value=0.005), TG (P value=0.001), and non-HDL-C (P value<0.001) tertiles for ACM event. Significant differences were also observed in the Kaplan–Meier curves for cardiovascular death between HDL-C (P value=0.003) and TG groups (P value=0.015). The survival curves of HDL-C groups were significantly variable in terms of cancer mortality (P value=0.048). In exploratory subgroup analyses, the inverse correlation between elevated HDL-C levels and mortality was predominantly more pronounced in older people and those with hypertension or diabetes, whereas it was less significant in younger and healthier individuals.
Conclusion: Abnormal levels of serum lipids, specifically low HDL-C concentration, are associated with an elevated risk of both non-CVD and CVD mortality. These relationships were widely seen across clinical categories, exhibiting substantially greater patterns in older participants and in persons with hypertension or diabetes. These findings indicate that HDL-C may assist in identifying individuals at increased mortality risk within this population.