Randomized, double-blind study on 15,607 subjects with high CVR, who received (a) atorvastatin + torcetrapib or (b) atorvastatin + placebo.
Although treatment with torcetrapib raised HDL-C 72% from the baseline (), it entailed an increase in cardiovascular mortality in these subjects (HR: 1.25; 95% CI: 1.09–1.44; ).
Prospective, multicentric, randomized, double-blind study on 1,188 patients with CAD who underwent intravascular ultrasonography and received (a) atorvastatin + torcetrapib or (b) atorvastatin + placebo.
Subjects on atorvastatin + torcetrapib had a 61% increase in HDL-C and a 20% decrease in LDL-C levels when compared to the group on atorvastatin + placebo. However, the former also suffered a greater rise in blood pressure (21.3% versus 8.2%) and incidence of hypertensive cardiovascular events (23.7% versus 10.6%), without significant differences in progression of atherosclerosis, as evaluated by intravascular ultrasonography.
850 heterozygotes with familial hypercholesterolemia were treated with 20, 40, or 80 mg of atorvastatin for a 4-week period, followed by (a) atorvastatin monotherapy or (b) atorvastatin + torcetrapib 60 mg for 24 months, and underwent ultrasonography for evaluation of intima-media thickness.
HDL-C levels were significantly higher in the atorvastatin + torcetrapib group (81.5 ± 22.6 mg/dL versus 52.4 ± 13.5 mg/dL; ), who also displayed lower LDL-C and TAG concentrations. Nevertheless, those on monotherapy were found to have greater intima-media thickness in the common carotid artery.
Mendelian randomization study which evaluated the association between the LIPG Asn396Ser SNP and incident myocardial infarction in 50,763 participants from six prospective cohort studies and case-control studies involving an additional 16,685 cases of myocardial infarction and 48,872 controls and proposed a genetic score combining 14 common SNP that exclusively associate with HDL cholesterol and then tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls.
The LIPG Asn396Ser allele had a prevalence of 2.6% and was associated with increased HDL-C, without effect on LDL-C y TAG. In meta-analysis, carrier status for Asn396Ser was associated with an increase of roughly 0.29 SD units in HDL-C (), with no associations to other risk factors. Nevertheless, this allele was not associated with myocardial infarction (OR: 0.99; 95% CI 0.88–1.11, ), without significant heterogeneity among the studies included (). Finally, a 1 SD increase in HDL-C due to genetic score was not associated with risk of myocardial infarction (OR: 0.93; 95% CI: 0.68–1.26, ).
The APOA1 gene was resequenced in 190 subjects, evaluating the effects of mutations on HDL-C levels, risk of ischemic heart disease, myocardial infarction, and mortality in 10,440 individuals from the prospective Copenhagen City Heart Study, who were followed for 31 years. Results were validated in an independent case-control study with 16,035 subjects.
The A164S mutation was found to be a predictor of ischemic heart disease (HR: 32; 95% CI: 1.6–6.5), myocardial infarction (HR: 5.5; CI 95% 2.6–11.7), and mortality (HR: 2.5; 95% CI: 1.3–4.8) in heterozygotes, in comparison to noncarriers. A164S heterozygotes also showed normal levels of Apo A-I, as well as HDL-C and other serum lipids.
Multiethnic, population-based cohort study on 2,416 adults free from CVD who were participants in the Dallas Heart Study, where the association between cholesterol efflux capacity and CVD incidence was assessed.
HDL-C levels were found to be unrelated to CVD incidence after adjustment for traditional cardiovascular risk factors. Cholesterol efflux capacity was associated with lower CVR, even after adjustment for HDL-C concentration, HDL particle concentration, and traditional cardiovascular risk factors (HR: 0.33; 95% CI: 0.19–0.55).
21 subjects with the Apo A-IMilano mutation were compared with age- and sex-matched control subjects from the same kindred and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HDL-C levels under the 10th percentile for their gender and age), regarding ultrasonographic findings in carotid arteries.
Subjects with hypoalphalipoproteinemia had greater intima-media thickness (0.86 ± 0.25 mm) than the control group (0.64 ± 0.12 mm) and subjects with the Apo A-IMilano mutation (0.63 ± 0.10 mm); . Moreover, subjects with hypoalphalipoproteinemia had a significantly higher prevalence of atherosclerotic plaques than both of the other groups, despite the lower HDL-C levels (19.8 ± 9.8 mg/dL, ).
Randomized, single-blind study on 15,781 subjects with recent diagnoses of acute coronary syndrome who received (a) dalcetrapib 600 mg daily or (b) placebo.
Subjects on dalcetrapib had a 31–40% increase in HDL-C levels, with minimal effects on LDL-C. Compared to placebo, the dalcetrapib group did not show significantly higher CVR (HR: 1.04; 95% IC: 0.93–1.15, ).
