Emerging Cholesterol Modulators for Atherosclerotic Cardiovascular Disease.

Experimental and clinical studies have conclusively demonstrated that lowering elevated low-density lipoprotein cholesterol levels results in fewer major adverse cardiac events. Over the past few decades, statins have become the mainstay of lipid-lowering therapy, contributing significantly to the reduction of lipids, and providing patients with a cost-effective approach. However, with growing evidence in support of combination therapies providing increased benefits to certain patient populations, such as those intolerant to statins, there is an urgent need to investigate the safety and efficacy of alternative lipid-lowering drugs. In this paper, we review the current alternative and adjuvant cholesterol targeting agents. We further discuss the clinical trials that have evaluated the safety and efficacy of these alternative and adjuvant therapies as well as their implications for practical use. These drugs target levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or lipoprotein(a) as treatments for hyperlipidemia and atherosclerotic cardiovascular disease.

Maximal Sustained Isokinetic Power at Exercise Intolerance is not Critical Power.

The asymptote of the hyperbolic power-duration relationship, critical power (CP), demarcates sustainable from non-sustainable exercise. CP is a salient parameter within the theoretical framework determining exercise tolerance. However, measuring CP is time consuming - typically 4 constant-power exercise tests to intolerance, or a 3-min all-out sprint is required.To determine whether 30 s of maximal isokinetic cycling, immediately following the limit of tolerance, approximates CP.Fifteen participants (7 women, 8 men, 23±5 yr, 71±12 kg, V̇O2peak 4.39±1.04 L·min-1; 61±9 mL·kg·min-1) completed 4 constant supra-CP exercise tests to intolerance. Each test was followed immediately by a 30 s maximal isokinetic effort at 80 rpm. Mean isokinetic power was compared to the known CP.Mean±SD CP was 159±47 W (CI95 133, 185 W). Maximal isokinetic power immediately following intolerance was greater (p<0.05) than CP in all but one comparison (181±51 vs. 159±47 W; p>0.07). However, this closest estimation, following the longest duration constant-power test, resulted in 21 W of mean bias and wide limits of agreement (±84 W).Isokinetic power measured immediately following intolerance consistently overestimated critical power. Thus, an adjunct of 30 s maximal isokinetic cycling immediately following the limit of tolerance does not approximate critical power.

Dynamics of Locomotor Fatigue during Supra-critical Power Exercise.

PURPOSE: We aimed to measure 1) the dynamics of locomotor fatigue during constant supra-critical power cycling and 2) the magnitude of any reserve in locomotor power at intolerance to constant and ramp-incremental cycling in recreationally active volunteers. METHODS: Fifteen participants (7 women and 8 men, 22 ± 3 yr, 3.34 ± 0.67 L·min V˙O2peak) completed ramp-incremental and very-heavy constant power (205 ± 46 W) exercise to the limit of tolerance. Immediately after intolerance, the ergometer was switched into the isokinetic mode, and participants completed a short (~5 s) maximal isokinetic effort at 70 rpm. The time course of locomotor fatigue during constant supra-critical power exercise was characterized with these short maximal isokinetic sprints at 30, 60, 120, and 180 s and at the limit of tolerance. Each bout was terminated after the isokinetic sprint. RESULTS: Constant power exercise duration was 312 ± 37 s. Isokinetic power production values at 30, 60, 120, and 180 s and at the limit of tolerance (at 312 ± 37 s) was 609 ± 165, 503 ± 195, 443 ± 157, 449 ± 133, and 337 ± 94 W, respectively. Of the total decline in isokinetic power, ~36% occurred within the first minute of exercise, and significant (P < 0.05) reductions in isokinetic power occurred at all time points versus the baseline maximal isokinetic power (666 ± 158 W). In addition, a significant power reserve of 132 ± 74 W (64% of the task requirement) and 119 ± 80 W (47%) was present at the limit of constant power and ramp-incremental exercise, respectively. CONCLUSIONS: Locomotor fatigue occurred rapidly during supracritical power exercise with pseudo-exponential kinetics. Instantaneous isokinetic power production at the limit of tolerance exceeded that of the task requirement, regardless of the constant or ramp work rate profile. Thus, the perceptual and physiologic limits were dissociated at the limit of tolerance in recreationally active volunteers.