Age and Cardiovascular Risk Attributable to Apolipoprotein B, Low-Density Lipoprotein Cholesterol or Non-High-Density Lipoprotein Cholesterol

Sniderman AD, Islam S, et al
J Am Heart Assoc. 2016 Oct 13;5(10)

Background

Apolipoprotein B (apoB) is a major determinant of cardiovascular (CV) risk and this risk rapidly increases with age. One might therefore assume that the CV risk associated with apoB particles increases with age but in contrast, several prospective epidemiological studies showed that apoB as well as LDL-c and total cholesterol (TC) appear to be more potent risk factors below the age of 70 compared to above the age of 70 [1-5].

To elucidate whether apoB particles create greater risk of a first myocardial infarction (MI) in younger individuals, apoB, TC, LDL-c, non-HDL-c, apoA-I and HDL-c levels were examined over a broad range of age. For this, data from the INTERHEART study had been used, which includes more than 25,000 participants (cases and controls). Age groups were <40, 40-50, 50-60, 60-70 and ≥70 years.

Main results

• In controls, the concentrations of apoB, TC and LDL-c were slightly but significantly higher in older controls (lowest vs. highest age group 88 vs 91 mg/100 mL; P trend = 0.003, 192 vs 200; P trend < 0.0001 and 117 vs 124; P trend <0.0001 resp.), whereas apoA-I and HDL-c were lower in older controls (115 vs. 124 and 39 vs 45 resp., both P trend < 0.0001).
• In cases, the concentrations of apoB, LDL-c and non-HDL-c were lower in older than younger cases (lowest vs. highest age group 100 vs 91, 133 vs 126 and 169 vs 154 mg/100 mL resp., all P trend < 0.0001), whereas apoA-I and HDL-c were significantly higher in younger compared to older cases (105 vs 116 and 36 vs 44 mg/100 mL resp., both P trend < 0.0001).
• Adjusted odds ratio (OR) for apoB, LDL-c and non-HDL-c were highest in the two lowest age groups and decreased steadily thereafter (lowest vs highest age group OR 1.51 vs 1.12, 1.38 vs 1.18 and 1.32 vs 1.08 resp., P trend < 0.0001 for all). The OR for all age groups was higher for apoB than for non-HDL-c, but not significantly for LDL-c.
• For apoA-I and HDL-c there were, except for those ≥70 years, little OR differences between different age groups.

Conclusion

In contrast to what might have been expected based on the fact that the risk of CV disease increases with age, the ORs of elevated levels of atherogenic lipid particles LDL-c, apoB and non-HDL-c significantly decreased with age and also the concentration of these markers decreased with age. Risk associated with HDL-c and apoA-I did not seem to vary with age. These relationships suggest that there is a greater relative benefit of preventative lipid-lowering in younger age groups.

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References

1. Batty GD, Shipley M, Smith GD, Kivimaki M. Long term risk factors for coronary heart disease and stroke: influence of duration of follow-up over four decades of mortality surveillance. Eur J Prev Cardiol. 2015;22:1139–1145.
2. Simons LA, Simons J, Friedlander Y, McCallum J. Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years. Atherosclerosis. 2001;159:201–208.
3. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358:2026–2033.
4. Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF. Lack of association between cholesterol and coronary heart disease mortality and morbidity and allcause mortality in persons older than 70 years. JAMA. 1994;272:1335–1340.
5. Clarke R, Lewington S, Youngman L, Sherliker P, Peto R, Collins R. Underestimation of the importance of blood pressure and cholesterol for coronary heart disease mortality in old age. Eur Heart J. 2002;23:286–293.