Context:
Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role.
Objective:
The objective of ...the study was to determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD.
Design:
This was a cross-sectional study.
Setting:
The study was conducted at a university hospital.
Patients:
Patients were recruited from outpatient clinics or from the general population (n = 188).
Interventions:
Measurement of hepatic triglyceride content by magnetic resonance spectroscopy, histology (liver biopsy), metabolic profile by means of an oral glucose tolerance test, and lipoprotein analyses were performed.
Outcomes:
Outcomes measured included standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, low-density lipoprotein (LDL) particle size/phenotype, and LDL/high-density lipoprotein subfractions), and insulin resistance.
Results:
Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared with patients without NAFLD. Despite small differences in triglycerides and high-density lipoprotein-cholesterol, patients with NAFLD had a significantly higher plasma apolipoprotein B to apolipoprotein A1 ratio (0.66 ± 0.02 vs 0.58 ± 0.02, P = .01) and smaller LDL particle size (216.2 ± 0.7 vs 219.4 ± 1.1 Å, P = .01). Of note, these differences between patients with/without NAFLD were independent of the presence of obesity. Severity of steatohepatitis did not significantly influence the lipoprotein profile. Worse atherogenic dyslipidemia was best predicted by the degree of liver fat accumulation and adipose tissue and systemic insulin resistance.
Conclusions:
NAFLD was associated with a worse atherogenic lipoprotein profile, regardless of similar body mass index and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease (nonalcoholic steatohepatitis).
Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins ...can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo.
In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio HR per SD, 1.03; 95% confidence interval CI, 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk.
In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
Background
Over a 14‐year period, age‐adjusted high total cholesterol (≥240 mg/dL) in the United States declined from 18.3% in 1999 to 2000 to 11.0% in 2013 to 2014, coinciding with the 2001 National ...Cholesterol Education Program Adult Treatment Panel (ATP)‐III guidelines that endorsed low‐density lipoprotein (LDL)‐cholesterol blood value goals. Statin treatment recommendations were revised by the American College of Cardiology and the American Heart Association (ACC/AHA) in November 2013 to a “risk‐based prescription” approach that did not utilize blood cholesterol values. This increased dosage and expanded the statin‐eligible population by an estimated 12.8 million US adults. These changes should further lower total and LDL cholesterol concentrations nationally.
Methods
We examined data from 507 752 patients nationally aged ≥16 years whose fasting bloods were sent to Boston Heart Diagnostics for direct LDL‐cholesterol measurements. Between 2012 and 2017, age‐adjusted concentrations were examined by analysis of covariance and LDL‐cholesterol ≥160 mg/dL by logistic regression.
Results
Contrary to expectations, age‐adjusted mean LDL‐cholesterol concentrations (±SE, mg/dL) increased significantly (P < 10−16) in men (2012:113.8 ± 0.3; 2013:115.3 ± 0.2; 2014:114.7 ± 0.2; 2015:116.0 ± 0.2; 2016:117.6 ± 0.2; and 2017:117.1 ± 0.2 mg/dL) and women (2012:119.5 ± 0.3; 2013:120.7 ± 0.2; 2014:119.8 ± 0.02; 2015:120.8 ± 0.2; 2016:122.7 ± 0.1; and 2017:123.8 ± 0.2 mg/dL). The percentage with LDL‐cholesterol ≥160 mg/dL also increased significantly (P < 10−9) in men and women. Similar results were obtained for ages 40 to 75 years olds (corresponding to ACC/AHA guidelines).
Conclusion
These results provide additional evidence that declining blood LDL‐cholesterol levels observed following the ATP‐III recommendations, did not further decline (actually increased) following the 2013 ACC/AHA recommendations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Statin-related myopathy (SRM) undermines drug adherence that is critical for achieving the benefits of lipid-lowering therapy. While the exact mechanism of SRM remains largely unknown, ...recent evidence supports specific genetic and immunologic influence on the development of intolerance. Genes of interest include those involved in the pharmacokinetics of statin response (i.e. drug metabolism, uptake transporters, and efflux transporters), pharmacodynamics (i.e. drug toxicity and immune-mediated myopathy), and gene expression. We examine the influence of genetic and immunologic variation on the pharmacokinetics, pharmacodynamics, and gene expression of SRM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, UL, UM, UPCLJ, UPUK
Objective To assess the clinical utility of measuring high-density lipoprotein (HDL) subfractions to assess coronary heart disease (CHD) risk. Methods Literature review of 80 published ...investigations. Results Measurements of HDL2b by gradient gel electrophoresis provided more consistent evidence of CHD risk than measurement of HDL2 cholesterol. Five of the seven studies that compared the extent or progression of atherosclerosis with gradient gel electrophoresis estimates of HDL subclasses (71%) assigned statistical significance to HDL2b. Ten of the 11 case-control comparisons (91%) reported lower HDL2b in cases. In contrast, of the 16 association studies relating HDL2 cholesterol and HDL3 cholesterol to extent of disease, five reported no significant relationships with either subfraction, two reported significant relationships with both HDL2 and HDL3 cholesterol, four reported significant relationships with HDL2 but not HDL3 cholesterol, and five reported relationships with HDL3 but not HDL2 cholesterol. Forty-five percent of the case-control comparisons reported that both HDL2 cholesterol and HDL3 cholesterol were significantly lower in cases than controls, 17% failed to find significance for either subfraction, and the remainder reported significantly lower values in cases for HDL2 cholesterol only (26%) or HDL3 cholesterol only (11%). On average, the case-control differences were similar for HDL2 (−0.12 ± 0.01 mmol/L) and HDL3 cholesterol (−0.10 ± 0.02 mmol/L), although relative to controls, the percent reduction was twice as great for HDL2 (−25.7 ± 2.9%) than HDL3 cholesterol (−12.1 ± 1.5%). Eight prospective studies were identified and four reported that both HDL2 and HDL3 predicted lower risk for CHD, one reported reductions in risk for HDL2 but not HDL3 cholesterol, and three reported reductions in risk for HDL3 but not HDL2 cholesterol. None of the prospective studies show that measurements of HDL cholesterol subfractions improve the identification of persons at risk. Conclusions HDL2 and HDL3 cholesterol do not distinguish cardioprotective differences between HDL subclasses. More extensive characterization of HDL particles by one or two dimensional gel electrophoresis, ion mobility, or ultracentrifugation may provide more specific information about CHD risk than the measurement of HDL cholesterol, HDL3 cholesterol, or HDL2 cholesterol.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Under “treat to risk” goals, low-density (LDL)-cholesterol follow-up measurements monitor statin compliance rather than titration to target levels, however, there is little evidence showing that ...more-frequent monitoring reduces LDL-cholesterol. We therefore tested whether frequency of blood tests significantly predicted lipoprotein improvements in a large anonymized clinical laboratory database. Differences (∆ ± SE) in total cholesterol, triglycerides, and LDL-cholesterol between baseline and follow-up visits were calculated for 97,548 men and 110,424 women whose physicians sent blood to Boston Heart Diagnostics for analysis between 2010 and 2017. When adjusted for age and follow-up duration, plasma concentration changes per each follow-up measurement in men and women respectively were −2.84 ± 0.10 mg/dL and −3.03 ± 0.10 mg/dL for total cholesterol, −3.78 ± 0.30 mg/dL and −2.26 ± 0.19 mg/dL for triglycerides, and −2.54 ± 0.09 mg/dL and −3.06 ± 0.09 mg/dL for LDL-cholesterol (all P < 10−16). Relative to baseline, significant decreases (P < 10−16) were observed for the 1st, 2nd, and 3rd follow-up measurements for total cholesterol (mean ± SE, men: −9.4 ± 0.1, −11.9 ± 0.2, −13.7 ± 0.3; women: −8.0 ± 0.1, −10.5 ± 0.2, −12.6 ± 0.3 mg/dL, respectively), triglycerides (men: −10.3 ± 0.4, −12.8 ± 0.5, −13.4 ± 0.7; women: −6.4 ± 0.2, −8.8 ± 0.4, −10.1 ± 0.5 mg/dL, respectively) and LDL-cholesterol (men: −7.8 ± 0.1, −9.9 ± 0.2, −11.1 ± 0.2; women: −6.9 ± 0.1, −9.0 ± 0.2, −10.7 ± 0.2 mg/dL, respectively). When adjusted for regression to the mean, 6.9%, 9.9% and 11.8% of men, and 5.7%, 9.7% and 11.5% of women, went from having an LDL-cholesterol ≥160 to <160 mg/dL for their 1st, 2nd, and 3rd follow-up measurements, respectively. We conclude that under usual physician care, total cholesterol, triglyceride, and LDL-cholesterol concentrations decreased progressively with increased physician monitoring within a large patient population.
•Current treat to risk goals recommend LDL monitoring to assess statin compliance.•Whether more frequent testing predict lipoprotein improvements is unknown.•LDL improvement per follow-up measurement was assessed in 207,972 patients.•LDL decreased 2.54 mg/dL in men and 3.06 mg/dL in women per follow-up measurement.•Total cholesterol and triglycerides also decreased with increased physician monitoring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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