Effect of age on the association of non-high-density-lipoprotein cholesterol and apolipoprotein B with cardiovascular mortality in a Mediterranean population with type 2 diabetes: the Casale Monferrato study

Abstract

Aims/hypothesis: Measurement of plasma apolipoprotein (Apo) B may improve prediction of cardiovascular risk, as it provides a measure of the total number of atherogenic particles. The aim of this population-based study was to compare the association of non-HDLcholesterol, ApoB and the ApoB:ApoA-I ratio with cardiovascular mortality in people with type 2 diabetes. Subjects and methods: We assessed the association of lipids, lipoprotein lipids and apolipoproteins with 11-year mortality from cardiovascular disease in the populationbased cohort of the Casale Monferrato Study (1,565 people with diabetes; median age 68.9 years), and determined the effect of age (≤70 and >70 years) on these relationships. Results: On the basis of 341 deaths from cardiovascular disease in 10,809 person-years of observation, there was a decreasing trend in risk adjusted for multiple factors across quartiles of total cholesterol, and LDL-and non-HDL-cholesterol in people aged >70 years, but no trend in those aged ≤70 years. Age did not affect the protective effect of HDL-cholesterol. ApoB and ApoB:ApoA-I were associated with outcome in people in both age groups independently of non-HDLcholesterol. After adjustment for multiple factors, including non-HDL-cholesterol, the hazard ratios for ApoB: ApoA-I in the upper vs lower quartile were 2.98 (95% CI 1.15-7.75; p for trend=0.009) for people aged ≤70 years and 1.94 (95% CI 1.20-3.13; p for trend=0.003) for those aged >70 years. Conclusions/interpretation: In this cohort of Mediterranean subjects with diabetes, ApoB and the ApoB:ApoA-I ratio were associated with cardiovascular disease mortality independently of non-HDLcholesterol. Our findings support the recommendation that ApoB and ApoA-I should be measured routinely in all people with diabetes, particularly in the elderly.

A Meta-Analysis of Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, and Apolipoprotein B as Markers of Cardiovascular Risk

“…These results pointed to a hierarchy of accuracy among the 3 markers, with apoB having the highest RRR, LDL-C having the lowest RRR, and non-HDL-C an intermediate RRR. Each individual study RRRs were significantly (PϽ0.05) Ͼ1.0 except for non-HDL-C in the Casale Monferrato study (Pϭ0.22) 19 and Copenhagen Heart women (Pϭ0.058) 13 and for LDL-C in the health professionals with diabetes (Pϭ0.08), 16 Casale Monferrato (Pϭ0.17), Copenhagen Heart women (Pϭ0.13), and Framingham Offspring (Pϭ0.13 in men; Pϭ0.07 in women; reported as significant when pooled, however) studies.…”

“…We chose a random-effects rather than a fixed-effects model for a number of reasons, among which was the fact that not all studies had the same mixture of clinical ischemic events, as follows: The Casale Monferrato study 19 was based only on fatal ischemic events; the INTERHEART study 22 and International Studies of Infarct Survival (ISIS) 23 were based only on nonfatal ischemic events; and the remainder included both nonfatal and fatal events. By choosing a random-effects model, we do not assume that the atherogenic parameters being compared have exactly the same relation to fatal as to nonfatal ischemic events.…”

Opening a New Lipid “Apo-thecary”: Incorporating Apolipoproteins as Potential Risk Factors and Treatment Targets to Reduce Cardiovascular Risk

“…[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] In the 52-country INTERHEART study, the Apo B:A-1 ratio accounted for 54% of the population-attributable risk of acute myocardial infarction (MI). Apo B was also superior to LDL cholesterol and non-HDL cholesterol in predicting coronary heart disease (CHD) ( Table 1).…”

“…15,98 Still, many clinicians justifiably contemplate which other atherogenic parameter needs to be altered to minimize atherosclerotic progression and cardiovascular events (Table 4). 8,23,24,[26][27][28][29][30][31]35,44,47,51,54,[99][100][101][102][103][104][105][106][107][108] Levels of Apo B or non-HDL cholesterol are in general superior to levels of LDL cholesterol in stratifying patient populations according to baseline (pretreatment) cardiovascular risk. With their ease of computation, their improvement in risk prediction over LDL cholesterol levels, their consistency with the current "cholesterol" paradigm familiar to practitioners, and their cost-effectiveness, non-HDL cholesterol levels seem to represent an attractive route to more informed decision making.…”

“…Despite having relatively "normal" LDL cholesterol and non-HDL cholesterol levels at baseline, this population, which had Clinical settings in which parameter provides additional risk Potential advantages and disadvantages of Lipid/lipoprotein stratification and/or treatment effectiveness information using parameter to guide risk assessment/treatment Apo B Evaluation of residual risk and monitoring therapeutic Can be used to identify the residual risk or "cholesterol-Apo B effectiveness in patients receiving statins for primary or mismatch/treatment gap" in many patients who achieve secondary prevention of CV events LDL-C and non-HDL-C target levels but not Statin therapy reduces LDL-C levels by a greater percentage correspondingly low population-equivalent Apo B targets. than it does Apo B levels ("cholesterol−Apo B This gap can be closed with more intensive therapy 101 mismatch") 8,47,54,99,100 Apo B is superior to lipid variables (including LDL-C, non-HDL-C, and TC:HDL-C ratio) in predicting on-treatment clinical events 8,29,35,44 Patients (eg, with type 2 DM, metabolic syndrome) having More closely associated with insulin resistance and markers of elevated TGs and TG-rich lipoproteins in the presence of metabolic syndrome than either LDL-C or non−HDL-C normal LDL-C and/or low HDL-C levels [27][28][29]51 levels 23 LDL-C may underestimate CV risk in these patients Evaluation of CV risk in patients with low baseline LDL-C There is a stoichiometric 1:1 relationship between numbers of levels (<130 mg/dL) potentially atherogenic particles (LDL-C, IDL-C, VLDL-C, In the JUPITER trial, the baseline LDL-C level cholesterol-rich remnant particles) and Apo B level (108 mg/dL) was in the 25th percentile of the US (1 molecule of Apo B per atherogenic particle). In contrast, population, whereas the baseline Apo B level the cholesterol contents of these particles' cores are (109 mg/dL) was in only the 60th percentile for men and heterogeneous; eg, LDL is a very long-lived species that 70th percentile for women 102,103 becomes depleted of cholesteryl esters over time and Apo B is more predictive of CV risk in those with LDL-C enzymatic activity/reverse cholesterol transport.…”