European Heart Journal Advance Access originally published online on August 1, 2008
European Heart Journal 2009 30(6):710-717; doi:10.1093/eurheartj/ehn347
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Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population
1 Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Building L8:03, S-17176 Stockholm, Sweden
2 Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic college of Medicine, Mayo Foundation, Rochester, MN 55905, USA
3 AstraZeneca, Södertälje, Sweden
Received 17 February 2008; revised 9 July 2008; accepted 11 July 2008; online publish-ahead-of-print 1 August 2008.
* Corresponding author. Tel: +46 8 51773222, Fax: +46 8 311298, Email: anders.hamsten{at}ki.se
Aims: Prospective studies indicate that apolipoprotein measurements predict coronary heart disease (CHD) risk; however, evidence is conflicting, especially in the US. Our aim was to assess whether measurements of apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) can improve the ability to predict CHD death beyond what is possible based on traditional cardiovascular (CV) risk factors and clinical routine lipid measurements.
Methods and results: We analysed prospectively associations of apolipoprotein measurements, traditional CV risk factors, and clinical routine lipid measurements with CHD mortality in a multi-ethnic representative subset of 7594 US adults (mean age 45 years; 3881 men and 3713 women, median follow-up 124 person-months) from the Third National Health and Nutrition Examination Survey mortality study. Multiple Cox-proportional hazards regression was applied. There were 673 CV deaths of which 432 were from CHD. Concentrations of apoB [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.09–3.61], apoA-I (HR 0.48, 95% CI 0.27–0.85) and total cholesterol (TC) (HR 1.17, 95% CI 1.02–1.34) were significantly related to CHD death, whereas high density lipoprotein cholesterol (HDL-C) (HR 0.68, 95% CI 0.45–1.05) was borderline significant. Both the apoB/apoA-I ratio (HR 2.14, 95% CI 1.11–4.10) and the TC/HDL-C ratio (HR 1.10, 95% CI 1.04–1.16) were related to CHD death. Only apoB (HR 2.01, 95% CI 1.05–3.86) and the apoB/apoA-I ratio (HR 2.09, 95% CI 1.04–4.19) remained significantly associated with CHD death after adjusting for CV risk factors.
Conclusion: In the US population, apolipoprotein measurements significantly predict CHD death, independently of conventional lipids and other CV risk factors (smoking, dyslipidaemia, hypertension, obesity, diabetes and C-reactive protein). Furthermore, the predictive ability of apoB alone to detect CHD death was better than any of the routine clinical lipid measurements. Inclusion of apolipoprotein measurements in future clinical guidelines should not be discarded.
Key Words: Apolipoprotein A-I • Apolipoprotein B • ApoB/apoA-I ratio • Cardiovascular risk factors • Cardiovascular mortality • Coronary heart disease • HDL-cholesterol • Outcomes • NHANES