Malnutrition-inflammation modifies the relationship of cholesterol with cardiovascular disease

Abstract

In moderate and severe CKD, the association of cholesterol with subsequent cardiovascular disease (CVD) is weak. We examined whether malnutrition or inflammation (M-I) modifies the risk relationship between cholesterol levels and CVD events in African Americans with hypertensive CKD and a GFR between 20 and 65 ml/min per 1.73 m². We stratified 990 participants by the presence or absence of M-I, defined as body mass index <23 kg/m² or C-reactive protein >10 mg/L at baseline. The primary composite outcome included cardiovascular death or first hospitalization for coronary artery disease, stroke, or congestive heart failure occurring during a median follow-up of 77 months. Baseline total cholesterol (212 ± 48 versus 212 ± 44 mg/dl) and overall incidence of the primary CVD outcome (19 versus 21%) were similar in participants with (n = 304) and without (n = 686) M-I. In adjusted analyses, the CVD composite outcome exhibited a significantly stronger relationship with total cholesterol for participants without M-I than for participants with M-I at baseline (P < 0.02). In the non-M-I group, the cholesterol-adjusted hazard ratio (HR) for CVD increased progressively across cholesterol levels: HR = 1.19 [95% CI; 0.77, 1.84] and 2.18 [1.43, 3.33] in participants with cholesterol 200 to 239 and ≥240 mg/dl, respectively (reference: cholesterol <200). In the M-I group, the corresponding HRs did not vary significantly by cholesterol level. In conclusion, the presence of M-I modifies the risk relationship between cholesterol level and CVD in African Americans with hypertensive CKD.

Figure 1.

Associations of the adjusted HRs with 95% confidence intervals for the primary composite cardiovascular disease outcome with total cholesterol (A; P = 0.002) and with non-HDL cholesterol (B; P = 0.008) are significantly different between the M-I and non–M-I groups. (A) The total cholesterol reference value is 200 mg/dl. Total cholesterol level was modeled nonparametrically by using restricted cubic spline with four degrees of freedom, where the knots are 144, 191, 226, and 288 mg/dl. (B) The non-HDL cholesterol reference value is 130 mg/dl. Non-HDL cholesterol level was modeled nonparametrically by using restricted cubic spline with four degrees of freedom, where the knots are 97, 143, 179, and 237 mg/dl. All models were adjusted for age, gender, pre-existing cardiovascular disease, baseline iodine 125-iothalamate GFR, annual income, abnormal electrocardiogram, randomization group, and statin use and were stratified by center.

Figure 2.

Higher total cholesterol level associates with a gradual and significantly greater cumulative incidence of the primary composite cardiovascular disease outcome only in participants without M-I. The P value is <0.001 for the non–M-I group and is 0.45 for the M-I group. Cumulative cardiovascular (CV) event by cholesterol categories: <200, 200 to 239, and ≥240 mg/dl.

Figure 3.

Higher non-HDL cholesterol level associates with a significantly greater cumulative incidence of the primary composite CVD outcome only in participants without M-I. The P value is 0.009 for the non–M-I group and is 0.47 for the M-I group. Cumulative cardiovascular (CV) event by non-HDL cholesterol categories: <130, 130 to 159, and ≥160 mg/dl.