Elevated high-sensitivity C-reactive protein as a risk marker of the attenuated relationship between serum cholesterol and cardiovascular events at older age. The ARIC Study

Abstract

The relationship between cholesterol and coronary heart disease (CHD) is attenuated at older age. We analyzed cholesterol level as a predictor of CHD in 8,947 participants from the Atherosclerosis Risk in Communities (ARIC) Study, a large multicenter cohort study that enrolled participants in 1987-1989 at 4 field centers in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Participants in the present analysis had no history of CHD and were stratified by age (<65 or ≥65 years) and high-sensitivity C-reactive protein (hs-CRP) level (<2 or ≥2 mg/L). Visit 4 (1996-1997) was the baseline for this analysis, with follow-up through 2008. Cholesterol level was significantly associated with CHD among younger participants, and cholesterol level was similarly predictive of CHD among older participants with an hs-CRP level of <2 mg/L. In contrast, among older participants with an hs-CRP level of 2 mg/L or higher, the association of CHD with total cholesterol level was borderline significant (hazard ratio = 1.14, 95% confidence interval: 1.00, 1.29), and the association of CHD with low-density lipoprotein cholesterol level was nonsignificant (hazard ratio = 1.10; 95% confidence interval: 0.96, 1.26). Among older persons with an elevated hs-CRP level, cholesterol level was significantly less predictive of CHD (P < 0.05), whereas for those with an hs-CRP level of <2 mg/L, there was no significant difference compared with younger participants. In conclusion, we found that among the young-old, the association of cholesterol level with CHD was strong when hs-CRP level was not elevated and weak when hs-CRP level was elevated. Therefore, hs-CRP level could be useful for stratifying the young-old to assess the strength of cholesterol level in CHD risk prediction.

Keywords: C-reactive protein; elderly persons; serum cholesterol.

Figure 1.

The association of crude coronary heart disease (CHD) incidence per 1,000 person-years of follow-up with total cholesterol category stratified by high-sensitivity C-reactive protein (hs-CRP) group, as measured at visit 4 (1996–1997) for participants less than 65 years of age (A) and 65–74 years of age (B) in the Atherosclerosis Risk in Communities Study, United States, 1987–2008. Lines without reference points represent the linear trend of the association between total cholesterol level and CHD incidence for each hs-CRP group.