Showing papers by "Scott M. Grundy published in 2016"

Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis

Abstract: Importance The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain. Objective To evaluate the association between lowering LDL-C and relative cardiovascular risk reduction across different statin and nonstatin therapies. Data Sources and Study Selection The MEDLINE and EMBASE databases were searched (1966-July 2016). The key inclusion criteria were that the study was a randomized clinical trial and the reported clinical outcomes included myocardial infarction (MI). Studies were excluded if the duration was less than 6 months or had fewer than 50 clinical events. Studies of 9 different types of LDL-C reduction approaches were included. Data Extraction and Synthesis Two authors independently extracted and entered data into standardized data sheets and data were analyzed using meta-regression. Main Outcomes and Measures The relative risk (RR) of major vascular events (a composite of cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, or stroke) associated with the absolute reduction in LDL-C level; 5-year rate of major coronary events (coronary death or MI) associated with achieved LDL-C level. Results A total of 312 175 participants (mean age, 62 years; 24% women; mean baseline LDL-C level of 3.16 mmol/L [122.3 mg/dL]) from 49 trials with 39 645 major vascular events were included. The RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was 0.77 (95% CI, 0.71-0.84;P Conclusions and Relevance In this meta-regression analysis, the use of statin and nonstatin therapies that act via upregulation of LDL receptor expression to reduce LDL-C were associated with similar RRs of major vascular events per change in LDL-C. Lower achieved LDL-C levels were associated with lower rates of major coronary events.

Comparison of visceral fat mass measurement by dual-X-ray absorptiometry and magnetic resonance imaging in a multiethnic cohort: the Dallas Heart Study.

Abstract: Visceral adipose tissue (VAT) mass, a risk factor for cardiometabolic complications of obesity, is usually measured by magnetic resonance imaging (MRI) but this method is not practical in a clinical setting. In contrast, measurement of VAT by dual-x-ray absorptiometry (DXA) appears to circumvent the limitations of MRI. In this study, we compared measurements of VAT mass by MRI and DXA in the large, multiethnic cohort of the Dallas Heart Study (DHS). About 2689 DHS participants underwent paired measurement of VAT by MRI and DXA. Sex-stratified analyses were performed to evaluate the correlation and agreement between DXA and MRI. Model validation was performed using bootstrapping and inter-reader variability was assessed. Mean age of the cohort was 44 years, with 55% female, 48% Black and 75% overweight/obese participants. Regression analysis showed a linear relationship between DXA and MRI with R2=0.82 (95% confidence interval (CI) 0.81–0.84) for females and R2=0.86 (95% CI 0.85–0.88) for males. Mean difference between methods was 0.01 kg for females and 0.09 kg for males. Bland–Altman analysis showed that DXA tended to modestly underestimate VAT compared with MRI at lower VAT levels and overestimate it compared with MRI at higher VAT levels. Results were consistent in analyses stratified by race, body mass index status, waist girth and body fat. Inter-individual reader correlation among 50 randomly selected scans was excellent (inter-class correlation coefficient=0.997). VAT mass quantification by DXA was both accurate and valid among a large, multiethnic cohort within a wide range of body fatness. Further studies including repeat assessments over time will help determine its long-term applicability.

Overnutrition, ectopic lipid and the metabolic syndrome

Abstract: The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome.

Does Dietary Cholesterol Matter

Abstract: An ongoing dispute in the nutrition field is whether dietary cholesterol contributes significantly to elevated serum cholesterol and to atherosclerotic disease. Carefully controlled metabolic studies have shown that high-cholesterol intakes cause moderate increases in serum cholesterol levels. It is been difficult to verify this in population studies because of confounding factors. Nonetheless, meta-analysis of controlled studies documents a cholesterol-raising action of dietary cholesterol. Most of this effect occurs in low-density lipoproteins (LDLs), but the cholesterol content of other lipoproteins can be increased as well. Moreover, population studies strongly suggest that dietary cholesterol is atherogenic beyond any rise in LDL concentrations. It must be emphasized that dietary cholesterol is only one of several dietary factors influencing serum cholesterol levels. Others include saturated fatty acids, trans fatty acids, soluble fiber, and total caloric intake. To achieve substantial serum cholesterol lowering, favorable changes in all of these factors must be combined. To maximize cardiovascular risk reduction, a lifetime of a healthy diet is needed. Reduced cholesterol intake is only one of several factors required to achieve such a diet. In addition, reduction of cholesterol absorption can enhance serum cholesterol lowering. This can be attained by the addition of plant sterols or plant stanols to the diet or by use of ezetimibe, a cholesterol absorption blocker. By combining dietary cholesterol reduction with other cholesterol-lowering modalities, it should be possible to substantially reduce atherosclerosis throughout life short of using cholesterol-lowering drugs that act systemically.

Dyslipidaemia in 2015: Advances in treatment of dyslipidaemia.

Abstract: Statins remain the first-line therapy for dyslipidaemia. In 2015, however, effectiveness in reducing serum cholesterol levels and decreasing rates of cardiovascular disease in combination with statins has been demonstrated for two new classes of drugs: cholesterol-absorption inhibitors and PCSK9 inhibitors. The latter rival statins in their capacity to lower cholesterol levels.