Low-density lipoprotein-lowering strategies: target versus maximalist versus population percentile.

Item does not contain fulltextPURPOSE OF REVIEW: Maximalist low-density lipoprotein (LDL)-lowering strategies such as lowering LDL as much as possible or, alternatively, using the most potent LDL-lowering regimens have become increasingly popular. Almost all attention has focused on the potential advantages of these approaches with little focus on their potential disadvantages. Moreover, it is increasingly assumed that the lower and lower is better and better approach is supported by unassailable evidence. RECENT FINDINGS: This article will examine how strongly the findings of the statin clinical trials actually support the maximalist strategy. We will also introduce a new approach, the population percentile strategy, which is based on the fact that the amount of cholesterol in LDL can differ substantially. When cholesterol-depleted LDL particles are present, LDL cholesterol (LDL-C) underestimates apolipoprotein B (apoB) and LDL particle number. Statins lower LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) more than they lower apoB and LDL particle number. This means that, even if LDL-C, non-HDL-C and apoB are equal markers of on-treatment risk, apoB is a better marker of the adequacy of LDL-lowering therapy. SUMMARY: Our analysis indicates that the LDL-lowering regimen should be tailored to the individual using a population percentile strategy to ensure the greatest number of patients receive the greatest overall benefit. With this approach, apoB is the best marker of the adequacy of LDL-lowering therapy.1 juli 201

Should preclinical vascular abnormalities be measured in asymptomatic adults to improve cardiovascular risk stratification?

Item does not contain fulltextPURPOSE OF REVIEW: Guideline groups have issued contradictory decisions as to the value of noninvasive tests in asymptomatic adults at intermediate cardiovascular risk. Reclassification has only recently been accepted as a critical criterion to determine the utility of a diagnostic test. The present review examines potential limitations in reclassification and evaluates the utility of carotid ultrasound, pulse wave velocity and ankle brachial index from a clinical perspective. RECENT FINDINGS: Reclassification is less useful than generally believed, because therapy is already indicated in the majority of patients at intermediate risk and it is far from clear that treatment should be withheld in those who are downgraded in risk. Moreover, the additional benefit from more intensive therapy is much less than often thought. Reproducibility, standardization and reference values of noninvasive tests are obligatory before introduction in clinical care. SUMMARY: Routine screening of all those at intermediate risk does not appear to be justified. Screening should be performed on those individuals in whom the noninvasive test changes clinical care, which is most apparent for individuals at intermediate risk with LDL level less than 2.5 mmol/l, in whom positive noninvasive tests will result in the start of statin treatment. The primary value of these tests should not be to determine risk but to identify preclinical anatomic disease

Phenotypes of hypertriglyceridemia caused by excess very-low-density lipoprotein

Item does not contain fulltextOBJECTIVE: To characterize the composition of very-low-density lipoprotein (VLDL) particles and the proportion of VLDL to total apolipoprotein B (apoB) particles in patients with hypertriglyceridemia caused by excess VLDL. METHODS: Subjects were selected from 2023 consecutive patients attending the Lipid Clinic at the Laval University Centre. Plasma lipids, apoB, and apoA-I were measured and chylomicron lipids and VLDL and LDL lipids and apoB determined after ultracentrifugation. Patients with hypertriglyceridemia caused by excess VLDL were divided into four groups on the basis of triglyceride and apoB. RESULTS: A total of 440 controls, 387 subjects with normotriglyceridemic hyperapoB, 38 with type III dysbetalipoproteinemia, 270 with mild hypertriglyceridemic normoapoB, 163 with moderate hypertriglyceridemic normoapoB, 458 with mild hypertriglyceridemic hyperapoB, and 295 subjects with moderate hypertriglyceridemic hyperapoB were compared. In patients with hypertriglyceridemia caused by excess VLDL, the VLDL particles were triglyceride and cholesterol-enriched. HyperapoB is associated with greater low-density lipoprotein (LDL) apoB than normoapoB, whereas greater triglycerides are associated with greater VLDL apoB. Thus, the ratio of VLDL apoB/total apoB was significantly less in those with mild hypertriglyceridemia compared with those with moderate hypertriglyceridemia, irrespective of the plasma apoB. CONCLUSIONS: The apoB phenotypes in hypertriglyceridemia caused by excess VLDL appear to be determined by the extent to which VLDL secretion increases, the extent to which VLDL particles can be converted to LDL particles, and the effects of core lipid exchange. More accurate characterization of hypertriglyceridemia caused by excess VLDL should lead to a better understanding of the determinants of VLDL clearance and conversion to LDL as well as of the atherogenic potential of VLDL

The spectrum of type III hyperlipoproteinemia

Item does not contain fulltextBACKGROUND: Type III hyperlipoproteinemia is a highly atherogenic dyslipoproteinemia characterized by hypercholesterolemia and hypertriglyceridemia due to markedly increased numbers of cholesterol-enriched chylomicron and very-low-density lipoprotein (VLDL) remnant lipoprotein particles. Type III can be distinguished from mixed hyperlipidemia based on a simple diagnostic algorithm, which involves total cholesterol, triglycerides, and apolipoprotein B (apoB). However, apoB is not measured routinely. OBJECTIVE: The objective of the present study was to determine if patients with type III could be distinguished from mixed hyperlipidemia based on lipoprotein lipids. METHODS: Classification was based first on total cholesterol and triglyceride and then on the apoB diagnostic algorithm using apoB plus total cholesterol plus triglycerides, and validated by sequential ultracentrifugation. Four hundred and forty normals, 637 patients with hypertriglyceridemia, and 714 with hypertriglyceridemia and hypercholesterolemia were studied. Plasma lipoproteins were separated by sequential ultracentrifugation and heparin-manganese precipitation. Cholesterol, triglyceride, and apoB were measured in plasma and isolated lipoprotein fractions. RESULTS: Of the 1351 patients with hypertriglyceridemia, 49 had type III hyperlipoproteinemia, as diagnosed by the apoB algorithm and validated by ultracentrifugation. Plasma triglycerides were higher in the type III subjects: 4.16 mmol/L (3.35-6.08, 25th-75th percentile), but there was considerable overlap with the hypertriglyceridemic subjects 2.65 mmol/L (1.91-4.20, 25th-75th percentile) and the combined hyperlipidemic subjects 3.02 mmol/L (2.07-5.32, 25th-75th percentile). Similarly, total cholesterol was 4.79 mmol/L (4.31-5.58, 25th-75th percentile) for type III vs 5.5 mmol/L (4.64-5.78, 25th-75th percentile) and 7.02 mmol/L (6.39-7.96, 25th-75th percentile), respectively. By contrast, as identified by the apoB algorithm, the VLDL-C/TG, VLDL-C/VLDL-TG, VLDL-C/VLDL apoB, and VLDL apoB/LDL apoB ratios were all higher in type III than in the other hypertriglyceridemic dyslipoproteinemias with the exception of type V as diagnosed by the apoB algorithm. CONCLUSION: Cholesterol and triglycerides cannot reliably distinguish type III hyperlipoproteinemia from mixed hyperlipidemia. Adding apoB and applying the apoB algorithm makes reliable diagnosis possible and easy. However, unless apoB is introduced into routine clinical care, type III hyperlipoproteinemia will often not be recognized. Given the cardiovascular risk associated with type III and its responsiveness to treatment, this should not be acceptable

A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk

Item does not contain fulltextBACKGROUND: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. METHODS AND RESULTS: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (PLDL-C (PLDL-C (P=0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy. CONCLUSIONS: These results further validate the value of apoB in clinical care

Preparing for a post-net-zero world

Current greenhouse gas emissions will continue to affect the climate even after we reach net-zero emissions. We must understand how and prepare for a cooling planet. For the last century, the planet has experienced warming due to humanity’s collective, albeit unequal, greenhouse gas emissions. The rise in global-average temperatures has been accompanied by rapidly warming land and slower warming oceans, rising sea levels and shrinking ice coverage. However, with global greenhouse gas emissions hopefully peaking soon and international, and some national and sub-national, targets in place to reach net-zero emissions (that is, a state where anthropogenic greenhouse gas emissions into the atmosphere are balanced by anthropogenic removal from the atmosphere), a new and very different climate is potentially on the horizon. Net-zero emissions would probably be followed by net-negative emissions (where anthropogenic removal of greenhouse gases exceeds anthropogenic emissions) as policies to support emissions reductions and greater carbon removal progress. If global net-zero greenhouse gas emissions are reached, then global cooling will probably follow. Under net-negative greenhouse gas emissions, this cooling would be even greater

A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation

Item does not contain fulltex