What measure from a lipid panel is the best predictor of cardiovascular risk?

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Evidence-Based Answer:

The ratio of total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) is the best predictor of total cardiovascular risk in the currently offered standard lipid panel. (SOR A, based on multiple prospective cohort studies.) The apoB/apoA-I ratio was shown to be superior in predicting risk of fatal myocardial infarction (MI) in 1 population, but the clinical importance of this finding is unclear.

A 2007 prospective cohort study of 3,322 middle-aged white participants compared different lipid measures for cardiovascular heart disease (CHD) prediction over 15 years. The incidence of the first CHD event was measured and risk ratios were calculated for various lipid markers. Adjusting for nonlipid risk factors, the ratio apoB/apoA predicted CHD with a hazard ratio (HR) per standard deviation increment of 1.39 (95% confidence interval [CI], 1.23–1.58) in men and 1.40 (95% CI, 1.16–1.67) in women. The incremental HR for TC/HDL-C was 1.39 (95% CI, 1.22–1.58) in men and 1.39 (95% CI, 1.17–1.66) in women. For the ratio of LDL-C/HDL-C, the incremental HR was 1.35 (95% CI, 1.18–1.54) in men and 1.36 (95% CI, 1.14–1.63) in women. The authors concluded that the data do not support apoB or apoA-I measurements in clinical practice when total cholesterol and HDL-C are available.1

In 2005, a 10-year prospective cohort study compared the clinical utility of total cholesterol, LDL-C, HDL-C, non-HDL-C, and apolipoproteins A-I and B100 among 15,632 healthy US women aged 45 years or older for the occurrence of future cardiovascular events. The HRs for future cardiovascular events were 1.62 (95% CI, 1.17–2.25) for LDL-C, 1.75 (95% CI, 1.30–2.38) for apoA-I, 2.08 (95% CI, 1.45–2.97) for total cholesterol, 2.32 (95% CI, 1.64–3.33) for HDL-C, 2.50 (95% CI, 1.68–3.72) for apoB, and 2.51 (95% CI, 1.69–3.72) for non-HDL-C. The HRs for the lipid ratios were 3.01 (95% CI, 2.01–4.50) for apoB/apoA-I, 3.18 (95% CI, 2.12–4.75) for LDL-C/HDL-C, 3.56 (95% CI, 2.31–5.47) for apoB/HDL-C, and 3.81 (95% CI, 2.47–5.86) for TC/HDL-C.2

Another recent prospective study of 1,414 men and 1,436 women aged 35 to 64 years without a prior coronary event investigated whether apolipoproteins are independent risk factors for incident coronary events and whether they are superior to the usual lipoprotein measurements in the assessment of CHD. The incidence of fatal and nonfatal MI and sudden cardiac death over a period of 13 years was examined. In both sexes, the predictive ability of the apoB/apoA-I ratio for incident coronary events was virtually identical to that of the TC/HDL-C ratio.3

In 2004, a large prospective cohort study (AMORIS) followed more than 100,000 Swedish men and women older than 40 years for 8 years, to determine whether the apoB/apoA ratio was superior to other cholesterol ratios in predicting risk of fatal MI. The apoB/apoA ratio was significantly better at identifying fatal MI (incremental HR 1.4 per standard deviation; 95% CI, 1.36–1.49 in men and 1.27–1.47 in women) than TC/HDL (incremental HR 1.1; 95% CI 1.10–1.15 in men and 1.11–1.17 in women) and LDL/HDL (incremental HR 1.1; 95% CI, 1.09–1.13 in men and 1.11–1.17 in women). The authors concluded that the apoB/apoA-I ratio is the single best predictor of fatal MI in both men and women.4

HelpDesk Answer From EBP,
Sarah George, DO Karen Lin, MD Beatrix Roemheld-Hamm, MD, PhD
UMDNJ-Robert Wood Johnson FMR New Brunswick, NJ
1. Ingelsson E, Schaefer EJ, Contois JH, et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA. 2007; 298(7):776–785. [LOE 1b]
2. Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005; 294(3):326–333. [LOE 1b]
3. Meisinger C, Loewel H, Mraz W, Koenig W. Prognostic value of apolipoprotein B and A-I in the prediction of myocardial infarction in middle-aged men and women: results from the MONICA/KORA Augsburg cohort study. Eur Heart J. 2005; 26(3):271–278. [LOE 1b]
4. Walldius G, Jungner I, Aastveit AH, Holme I, Furberg CD, Sniderman AD. The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk. Clin Chem Lab Med. 2004; 42(12):1355–1363. [LOE 1b]

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