Serum non-high-density lipoprotein cholesterol concentration and risk of death from cardiovascular diseases among U.S. adults with diagnosed diabetes: the Third National Health and Nutrition Examination Survey linked mortality study

Abstract

Background: Non-high-density lipoprotein cholesterol (non-HDL-C) measures all atherogenic apolipoprotein B-containing lipoproteins and predicts risk of cardiovascular diseases (CVD). The association of non-HDL-C with risk of death from CVD in diabetes is not well understood. This study assessed the hypothesis that, among adults with diabetes, non-HDL-C may be related to the risk of death from CVD.

Methods: We analyzed data from 1,122 adults aged 20 years and older with diagnosed diabetes who participated in the Third National Health and Nutrition Examination Survey linked mortality study (299 deaths from CVD according to underlying cause of death; median follow-up length, 12.4 years).

Results: Compared to participants with serum non-HDL-C concentrations of 35 to 129 mg/dL, those with higher serum levels had a higher risk of death from total CVD: the RRs were 1.34 (95% CI: 0.75-2.39) and 2.25 (95% CI: 1.30-3.91) for non-HDL-C concentrations of 130-189 mg/dL and 190-403 mg/dL, respectively (P = 0.003 for linear trend) after adjustment for demographic characteristics and selected risk factors. In subgroup analyses, significant linear trends were identified for the risk of death from ischemic heart disease: the RRs were 1.59 (95% CI: 0.76-3.32) and 2.50 (95% CI: 1.28-4.89) (P = 0.006 for linear trend), and stroke: the RRs were 3.37 (95% CI: 0.95-11.90) and 5.81 (95% CI: 1.96-17.25) (P = 0.001 for linear trend).

Conclusions: In diabetics, higher serum non-HDL-C concentrations were significantly associated with increased risk of death from CVD. Our prospective data support the notion that reducing serum non-HDL-C concentrations may be beneficial in the prevention of excess death from CVD among affected adults.

Figure 1

Estimated relative risk of death among U.S. adults aged 20 years and older with diagnosed diabetes, the NHANES III Linked Mortality Study, 1988-2006. The red solid line indicates the fitted relationship between the relative risk of death from total CVD (A), IHD (B), stroke (C), and other CVD (D) in relation to the continuum of serum non-HDL-C concentrations with a 3-knot cubic regression spline. The blue dashed lines indicate the 95% confidence intervals surrounding the estimates. Adults with a serum non-HDL-C concentration of 130 mg/dL were set as the reference group. Relative risks (hazard ratios) and their 95% CIs were adjusted for sex, race/ethnicity, education attainment, diabetes duration, body mass index, leisure-time physical activity, smoking status, alcohol consumption, systolic blood pressure, serum HDL-C concentration, glomerular filtration rate, C-reactive protein, glycated hemoglobin A1C, and self-reported use of prescribed medicine to lower blood cholesterol. N = 1,122. To convert non-HDL-C concentration in mg/dL to mmol/L, multiply by 0.02586.N Abbreviations: CVD, cardiovascular disease; IHD, ischemic heart disease; NHANES III, Third National Health and Nutrition Examination Survey; Non-HDL-C, non-high-density lipoprotein cholesterol.

Figure 2

Hazard ratios of death among U.S. adults aged 20 years and older with diagnosed diabetes, the NHANES III Linked Mortality Study, 1988-2006. Unadjusted (blue dots) and adjusted (red dots) hazard ratios of death from total CVD (A), IHD (B), stroke (C), and other CVD (D) and their 95% CIs (high-low lines) were adjusted for sex, race/ethnicity, education attainment, diabetes duration, body mass index, leisure-time physical activity, smoking status, alcohol consumption, systolic blood pressure, serum HDL-C concentration, glomerular filtration rate, C-reactive protein, glycated hemoglobin A1C, and self-reported use of prescribed medicine to lower blood cholesterol. Adults with a serum non-HDL-C concentration below 130 mg/dL were set as the reference group. N = 1,122. To convert non-HDL-C concentration in mg/dL to mmol/L, multiply by 0.02586. Abbreviations: CVD, cardiovascular disease; IHD, ischemic heart disease; NHANES III, Third National Health and Nutrition Examination Survey; Non-HDL-C, non-high-density lipoprotein cholesterol.