1.
The 2018 AHA/ACC/Multi-Society Cholesterol guidelines: Looking at past, present and future.
Stone, NJ, Grundy, SM
Progress in cardiovascular diseases. 2019;(5):375-383
Abstract
The authors review more than three decades of progress in providing clinicians and patients with guidance on risk assessment, patient evaluation and cholesterol management. Beginning with the National Cholesterol Education Program's Initial Adult Treatment Panel report, the cholesterol guidelines increasingly reflect the progress made in understanding the benefits of improved lifestyle and nutrition to improve lipid profiles, major risk factors and reduce ASCVD risk. Moreover, they now provide qualitative and quantitative assessment tools to guide appropriate risk reduction LDL-C lowering therapy. Use of the Pooled Cohort Equations to determine Low, Borderline, Intermediate and High 10-year ASCVD risk is now joined by recognition of conditions and biomarkers that enhance ASCVD risk. This personalizes the risk discussion for the patient. An important addition is the selective use of coronary artery calcium (CAC) scoring to reclassify risk in patients at borderline or intermediate risk, but for whom a risk decision regarding statin therapy is uncertain. In secondary prevention, current guidelines provide criteria for determining a "very high" risk group in whom risk is especially high and in whom aggressive LDL-C lowering can be shown to provide increased absolute benefit. Current guidelines provide a comprehensive look at children and adolescents, young adults, elderly, women and issues specific to women through the life course. They provide guidance for those adults at risk due to severe hypercholesterolemia, persistent hypertriglyceridemia after secondary causes have been addressed, those with inflammatory disorders and HIV, those adults with chronic kidney disease, and those affected by issues of race/ethnicity. They conclude with a brief summary of recommendations emphasizing important concepts for providing safety with LDL-C lowering therapy. This combination of best external evidence and clinical expertise from the expert panel should provide a solid foundation for lipid management of patients at risk for or with clinical ASCVD.
2.
Robustness and evidence of mechanisms in early experimental atherosclerosis research.
Parkkinen, VP
Studies in history and philosophy of biological and biomedical sciences. 2016;:44-55
Abstract
This article considers the evaluation of experimental evidence for a causal relation between cholesterol and atherosclerosis from the beginning of the 1900s until the late 1950s. It has been argued that the medical community failed to see the implications of this early research, and at first unjustifiably rejected a causal link between cholesterol and atherosclerosis. This article argues to the contrary that the medical community was justified to conclude based on the experimental evidence that cholesterol (dietary or blood) is probably not an effective target for preventive treatment. However, the evidence would have been sufficient to ascribe to cholesterol a contributing causal role in atherosclerotic heart disease. This view is argued for based on a rational reconstruction of the researchers' evaluation of evidence, specifically, the robustness of evidence for a manipulable dependence between cholesterol and atherosclerosis on the one hand, and the evidence for a mediating mechanism on the other. The case study is used to illustrate that robustness is a feasible methodological principle even when evidence is discordant, and evidence of mechanism should be evaluated on a par with evidence of statistical dependence in establishing causal claims.
3.
Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.
Pastore, RL, Brooks, JT, Carbone, JW
Nutrition research (New York, N.Y.). 2015;(6):474-9
Abstract
Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations.
4.
Beyond cholesterol lowering: pleiotropic effects of bile acid binding resins against cardiovascular disease risk factors in patients with metabolic syndrome.
Yamaoka-Tojo, M, Tojo, T, Izumi, T
Current vascular pharmacology. 2008;(4):271-81
Abstract
Prospective epidemiologic studies have shown that dyslipidemia and hyperglycemia are major risk factors for atherosclerotic cardiovascular diseases. Undesirable metabolic conditions are observed to coexist in patients with metabolic syndrome, which is an important risk factor for cardiovascular disease. To prevent cardiovascular disease, a pleiotropic agent is needed to improve the metabolic disorder in patients with metabolic syndrome. Bile acid binding resins increase the fecal excretion of bile acids. The decrease in bile acids returned to the liver leads to an up-regulation of hepatic low-density lipoprotein (LDL) receptor activity, which decreases LDL cholesterol (LDL-C) in the circulation and increases high-density lipoprotein cholesterol. On the other hand, bile acids can also regulate the transcription of genes involved in LDL-C synthesis and cholesterol homeostasis via nuclear hormone receptors. Consequently, these receptors may represent novel therapeutic targets for dyslipidemia and provide insight into the role of the bile acid pathway in other metabolic processes. This review focuses on the recent findings on bile acid binding resins and cardiovascular disease risk factors. Moreover, known and proposed mechanisms of how bile acid binding resins may improve glucose and energy metabolism are discussed; these effects may help to explain the mechanisms by which bile acid binding resins may reduce cardiovascular disease.