Serum Non-High-Density Lipoprotein Cholesterol and Risk of Cardiovascular Disease in Community Dwellers with Chronic Kidney Disease: the Hisayama Study

Abstract

Aim: It is not clear whether elevated serum non-high-density lipoprotein cholesterol (non-HDL-C) levels are a risk factor for cardiovascular disease (CVD) in subjects with chronic kidney disease (CKD) in the general population.

Methods: A total of 2,630 community-dwelling Japanese subjects (1,107 men and 1,523 women) without history of CVD and aged ≥40 years were prospectively followed up for an average of 19 years, and the association between serum non-HDL-C levels and the incidence of type-specific CVD was estimated using a Cox proportional hazards model. CKD was defined as estimated glomerular filtration rate ＜60 mL/min/1.73 m² or proteinuria (≥1＋ on dipstick).

Results: At baseline, 357 subjects had CKD. During the follow up, 186 coronary heart disease (CHD) and 277 stroke events occurred. The age- and sex-adjusted incidence of CHD was significantly higher in subjects with higher non-HDL-C levels, both in those with and without CKD. In the CKD group, the risk of CHD was significantly higher in those with non-HDL-C levels of 150- 189 mg/dL [adjusted hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.04-4.77] and those with levels ≥190 mg/dL (adjusted HR, 3.20; 95% CI, 1.46-7.03) than in those with levels ＜150 mg/dL. In the non-CKD group, the risk of CHD was significantly higher only in those with nonHDL-C levels ≥190 mg/dL (adjusted HR, 2.12; 95% CI, 1.33-3.38). However, no such association was observed for the risk of stroke.

Conclusions: Our findings suggest that higher serum non-HDL-C levels are associated with greater risk of CHD in subjects with and without CKD and that this association is greater in subjects with CKD than in those without CKD.

Keywords: Cardiovascular disease; Chronic kidney disease; Cohort study; Non-high-density lipoprotein cholesterol; Risk factors.

Fig. 1.

Multivariable-adjusted HR for the development of coronary heart disease according to the CKD status and serum non-HDL-C levels CKD was defined as proteinuria (dipstick ≥ 1+) or estimated glomerular filtration rate < 60 mL/min/1.73 m², which was calculated using the modified Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSNCKDI) equation. Adjusted for age, sex, systolic blood pressure, antihypertensive medication, diabetes, body mass index, serum albumin and high-sensitivity C-reactive protein levels, electrocardiogram abnormalities, smoking habits, alcohol intake, and regular exercise Abbreviations: CKD, chronic kidney disease; non-HDL-C, non-high-density lipoprotein cholesterol; HR, hazard ratio.

Supplementary Fig. 1.

Multivariable-adjusted HR for the development of coronary heart disease according to CKD status and serum non-HDL-C levels (CKD defined by eGFR using the CKD-EPI equation) Adjusted for age, sex, systolic blood pressure, antihypertensive medication, diabetes, body mass index, serum albumin, serum high-sensitivity C-reactive protein, electrocardiogram abnormalities, smoking habits, alcohol intake, and regular exercise. Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; non-HDL-C, non-high-density lipoprotein cholesterol; HR, hazard ratio.