Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis

Abstract

Background: Worldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk.

Methods and results: We examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, ≥ 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol ≥ 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol <1.03 mmol/L (40 mg/dL) for men or <1.29 mmol/L (50 mg/dL) for women, and triglycerides ≥ 1.69 mmol/L (150 mg/dL). Our main outcome measure was incident CVD (myocardial infarction, angina resulting in revascularization, resuscitated cardiac arrest, stroke, cardiovascular death). Over a median follow-up of 7.6 years, more than half of events (55%) occurred in the 21% of participants with CAC ≥ 100. Conversely, 65% of events occurred in participants with 0 or 1 LA. In those with CAC ≥ 100, CVD rates ranged from 22.7 to 29.5 per 1000 person-years across LA categories. In contrast, with CAC=0, CVD rates ranged from 2.7 to 5.9 per 1000 person-years across LA categories. Individuals with 0 LA and CAC ≥ 100 had a higher event rate compared with individuals with 3 LA but CAC=0 (22.7 versus 5.9 per 1000 person-years). Similar results were obtained when we classified LA using data set quartiles of total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or low-density lipoprotein particle concentration and guideline categories of low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol.

Conclusions: CAC may have the potential to help match statin therapy to absolute CVD risk. Across the spectrum of dyslipidemia, event rates similar to secondary prevention populations were observed for patients with CAC ≥ 100.

Keywords: atherosclerosis; cardiovascular diseases; cholesterol; computed tomography.

Figure 1

Flowchart illustrating study population. MESA = Multi-Ethnic Study of Atherosclerosis.

Figure 2

Distribution of CAC by (A) LA and (B) TC/HDL-C Quartiles. CAC = coronary artery calcium score; LA = lipid abnormality; TC/HDL-C = ratio of total cholesterol to high-density lipoprotein cholesterol.

Figure 2

Distribution of CAC by (A) LA and (B) TC/HDL-C Quartiles. CAC = coronary artery calcium score; LA = lipid abnormality; TC/HDL-C = ratio of total cholesterol to high-density lipoprotein cholesterol.

Figure 3

Cumulative incidence of CVD events associated with CAC strata by (A) LA and (B) TC/HDL-C Quartiles. An unadjusted Nelson-Aalen cumulative function was used. CVD = atherosclerotic cardiovascular disease; abbreviations otherwise per Figure 2.

Figure 3

Cumulative incidence of CVD events associated with CAC strata by (A) LA and (B) TC/HDL-C Quartiles. An unadjusted Nelson-Aalen cumulative function was used. CVD = atherosclerotic cardiovascular disease; abbreviations otherwise per Figure 2.

Figure 4

CVD events per 1,000 person-years by strata of CAC and (A) LA or (B) TC/HDL-C Quartiles. Abbreviations per Figure 2.

Figure 4

CVD events per 1,000 person-years by strata of CAC and (A) LA or (B) TC/HDL-C Quartiles. Abbreviations per Figure 2.

Figure 5

CVD events per 1,000 person-years by strata of CAC and (A) LDL-C or (B) non-HDL-C levels based on NCEP ATP categories. LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; NCEP ATP = National Cholesterol Education Program Adult Treatment Panel; abbreviations otherwise per Figures 2 and 3.

Figure 5

CVD events per 1,000 person-years by strata of CAC and (A) LDL-C or (B) non-HDL-C levels based on NCEP ATP categories. LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; NCEP ATP = National Cholesterol Education Program Adult Treatment Panel; abbreviations otherwise per Figures 2 and 3.