Macrovascular Residual Risk Studies

Figure. Change in risk of acute myocardial infarction associated with a 1-SD change in cholesterol and apolipoprotein ratios in different ethnic groups.

COMMENT

One of the main strengths of the INTERHEART study is that it was conducted in a large number of patients and a large number of controls. The authors stress that a large population size was mandatory to ensure that “real differences in predictive power would not be obscured by the close correlation that exists between cholesterol and apolipoproteins,” especially when comparisons were made inside each ethnic group. Indeed, except for apolipoprotein B48-containing chylomicrons (and their remnants), all other atherogenic lipoprotein particles contains a single molecule of apolipoprotein B100 (ApoB), including LDL, the predominant atherogenic lipoprotein. ApoA-I is the hallmark lipoprotein of HDL.

The main result of INTERHEART is that the ApoB/ApoA-I ratio is a substantially better predictor of myocardial infarction than cholesterol ratios (TC/HDL-C and LDL-C/HDL-C). ApoB, the numerator, was a better predictor than LDL cholesterol. This is consistent with the fact that in people with atherosclerotic disease, LDL-C may be less representative of the number of LDL particles, when the latter are small and dense (whereas ApoB is unaffected by lipoprotein size, and mostly accounts for LDL-related apolipoprotein) and/or when LDL-C is computed using Friedewald’s formula in patients with raised triglycerides. The ratio denominator, ApoA-I was a better inverse predictor than HDL-C.

The INTERHEART findings are in line with those of the AMORIS cohort study1 conducted in 69,030 men and 57,168 women. In particular, the risk associated with a 1-SD change in the ApoB/ApoA-I ratio was virtually identical in both studies.

The measurement of ApoB and ApoA-I is simple and can be done with samples obtained from fasting or non-fasting individuals. The authors recommend to include these apolipoproteins in routine assessment of cardiovascular risk. A lesson can also be drawn in terms of reduction of residual cardiovascular risk. Through their action on cholesterol synthesis and LDL catabolism, statins markedly reduce the level of ApoB. The INTERHEART findings strongly suggest that therapeutic interventions able to raise ApoA-I may favorably impact on residual cardiovascular risk in patients treated with statins.