Effects of weight change on apolipoprotein B-containing emerging atherosclerotic cardiovascular disease (ASCVD) risk factors.

BACKGROUND AND AIMS: Non-high-density (HDL)-cholesterol, low-density lipoprotein (LDL)-particle number, apolipoprotein B, lipoprotein(a) (Lp(a)), and small-dense (sdLDL) and large-buoyant (lbLDL) LDL-subfractions are emerging apo B-containing atherosclerotic cardiovascular disease (ASCVD) risk factors. Current guidelines emphasize lifestyle, including weight loss, for ASCVD risk management. Whether weight change affects these emerging risk factors beyond that predicted by traditional triglyceride and LDL-cholesterol measurements remains to be determined. METHOD: Regression analyses of fasting ∆apo B-containing lipoproteins vs. ∆BMI were examined in a large anonymized clinical laboratory database of 33,165 subjects who did not report use of lipid-lowering medications. Regression slopes (±SE) were estimated as: *∆mmol/L per ∆kg/m2, †∆g/L per ∆kg/m2, ‡∆% per ∆kg/m2, and §∆µmol/L per ∆kg/m2. RESULTS: When adjusted for age, ∆BMI was significantly related to ∆nonHDL-cholesterol (males: 0.0238 ± 0.0041, P = 7.9 × 10- 9; females: 0.0330 ± 0.0037, P < 10- 16)*, ∆LDL-particles (males: 0.0128 ± 0.0024, P = 2.1 × 10- 7; females: 0.0114 ± 0.0022, P = 3.2 × 10- 7)*, ∆apo B (males: 0.0053 ± 0.0010, P = 7.9 × 10- 8; females: 0.0073 ± 0.0009, P = 2.2 × 10- 16)†, ∆sdLDL (males: 0.0125 ± 0.0015, P = 2.2 × 10- 16; females: 0.0128 ± 0.0012, P < 10- 16)*, ∆percent LDL carried on small dense particles (%sdLDL, males: 0.296 ± 0.035, P < 10- 16; females: 0.221 ± 0.023, P < 10- 16)‡, ∆triglycerides (males: 0.0358 ± 0.0049, P = 2.0 × 10- 13; females: 0.0304 ± 0.0029, P < 10- 16)*, and ∆LDL-cholesterol (males: 0.0128 ± 0.0034, P = 0.0002; females: 0.0232 ± 0.0031, P = 1.2 × 10- 13)* in both males and females. Age-adjusted ∆BMI was significantly related to ∆lbLDL in females (0.0098 ± 0.0024, P = 3.9 × 10- 5)* but not males (0.0007 ± 0.0026, P = 0.78)*. Female showed significantly greater increases in ∆LDL-cholesterol (P = 0.02) and ∆lbLDL (P = 0.008) per ∆BMI than males. ∆BMI had a greater effect on ∆LDL-cholesterol measured directly than indirect estimate of ∆LDL-cholesterol from the Friedewald equation. When sexes were combined and adjusted for age, sex, ∆triglycerides and ∆LDL-cholesterol, ∆BMI retained residual associations with ∆nonHDL-cholesterol (0.0019 ± 0.0009, P = 0.03)*, ∆LDL-particles (0.0032 ± 0.0010, P = 0.001)*, ∆apo B (0.0010 ± 0.0003, P = 0.0008)†, ∆Lp(a) (- 0.0091 ± 0.0021, P = 1.2 × 10- 5)§, ∆sdLDL (0.0001 ± 0.0000, P = 1.6 × 10- 11)* and ∆%sdLDL (0.151 ± 0.018, P < 10- 16) ‡. CONCLUSIONS: Emerging apo B-containing risk factors show associations with weight change beyond those explained by the more traditional triglyceride and LDL-cholesterol measurements.

Coronary artery calcium testing: A call for universal coverage.

Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.

The importance of cholesterol follow-up testing under current statin treatment guidelines.

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 (∆ ±â€¯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 ±â€¯0.10 mg/dL and -3.03 ±â€¯0.10 mg/dL for total cholesterol, -3.78 ±â€¯0.30 mg/dL and -2.26 ±â€¯0.19 mg/dL for triglycerides, and -2.54 ±â€¯0.09 mg/dL and -3.06 ±â€¯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 ±â€¯SE, men: -9.4 ±â€¯0.1, -11.9 ±â€¯0.2, -13.7 ±â€¯0.3; women: -8.0 ±â€¯0.1, -10.5 ±â€¯0.2, -12.6 ±â€¯0.3 mg/dL, respectively), triglycerides (men: -10.3 ±â€¯0.4, -12.8 ±â€¯0.5, -13.4 ±â€¯0.7; women: -6.4 ±â€¯0.2, -8.8 ±â€¯0.4, -10.1 ±â€¯0.5 mg/dL, respectively) and LDL-cholesterol (men: -7.8 ±â€¯0.1, -9.9 ±â€¯0.2, -11.1 ±â€¯0.2; women: -6.9 ±â€¯0.1, -9.0 ±â€¯0.2, -10.7 ±â€¯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.

Effects of weight change on HDL-cholesterol and its subfractions in over 28,000 men and women.

BACKGROUND: Changes in body mass index (ΔBMI) have well-established relationships to changes in high-density lipoprotein (ΔHDL)-cholesterol concentrations; however, their relationships to ΔHDL subfractions are less well understood. OBJECTIVE: Assess the associations between ΔHDL and ΔBMI in a very large cohort. METHOD: Age and sex-adjusted Δapo A1 concentrations were measured within 10 HDL subfractions in 14,121 women and 13,969 men using two-dimensional HDL-mapping. Significance was identified at .01 < P ≤ .05 (*), .001 < P ≤ .01 (†), .0001 < P ≤ .001 (‡), and P ≤ .0001 (§). RESULTS: ΔBMI was significantly associated with Δα-1 (very large HDL, slope ± SE, females: -0.39 ± 0.07§; males: -0.51 ± 0.05§), Δα-3 (medium HDL, females: 0.18 ± 0.04§; males: 0.19 ± 0.04§), and Δα-4 (small HDL, females: 0.14 ± 0.03§; males: 0.15 ± 0.04§ mg/dL per kg/m2). As a percent of baseline, the changes in α-1 per ΔBMI were nearly twice as great as the changes in HDL-cholesterol per ΔBMI in both males (-1.53% vs -0.77%) and females (-0.79% vs -0.42%). HDL-cholesterol decreased significantly in healthy-weight patients who became overweight, overweight patients who became class I or class II obese, class I obese patients who became class II obese, and class II obese patients who became class III. In contrast, HDL-cholesterol increased in class III obese patients who became class II or class I, class II obese patients who became class I or overweight, class I patients who became overweight or healthy weight, overweight patients who became healthy weight, and healthy weight patients who became underweight. CONCLUSIONS: Weight change significantly affects HDL-cholesterol concentrations throughout the obesity spectrum. ΔBMI's effect on Δα-1 was nearly twice as great as its effect on HDL-cholesterol.

Trends in low-density lipoprotein-cholesterol blood values between 2012 and 2017 suggest sluggish adoption of the recent 2013 treatment guidelines.

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.

Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD.

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).

Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Genetic and immunologic susceptibility to statin-related myopathy.

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.

Omega-3 Fatty Acid Blood Levels Clinical Significance Update.

The potential benefit of fish oil (omega-3 fatty acids) consumption to reduce cardiovascular disease (CVD) risk remains controversial. Some investigations report reduced CVD risk associated with fish or fish oil consumption while others report no benefit. This controversy is in part resolved when consideration is given to omega-3 blood levels in relation to CVD risk as well as blood levels achieved in clinical trials of omega-3 supplementation and CVD benefit. There is a wide variation in omega-3 blood levels achieved between individuals in response to a given dose of an omega-3 supplement. Many studies tested a daily dose of 1 gram omega-3 supplementation. The individual variation in blood omega-3 levels achieved in response to a fixed daily dose helps to explain why some individuals may obtain CVD protection benefit while others do not due to failure to achieve a therapeutic threshold. Recent development of a population range in a United States population helps to provide clinical guidance since population omega-3 blood level ranges may vary due to environmental and genetic reasons. Omega-3 supplementation may also be of benefit in reducing the adverse impact of air pollution on CVD risk.

Genetics and personalized medicine--a role in statin therapy?

Pharmacogenetics uses the genetic variation in metabolic pathways to identify groups of patients who may respond differently in terms of therapeutic and adverse effects. Much clinical interest lies in drug metabolism and the opportunity to improve prescribing efficacy and safety. Owing to widespread use and increasing concern regarding side effects, statins are of significant interest in this area. Among other benefits, statins have been shown to improve lipid profiles and reduce coronary heart disease event rates in many populations. However, variability in drug response exists, and genetic variability may be a contributing factor. Our primary goal is to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genome-wide association studies and the candidate gene approach.

Blood cholesterol trends 2001-2011 in the United States: analysis of 105 million patient records.

OBJECTIVES: We report annual trends in low density lipoprotein cholesterol (LDL-C) from an in-care patient population of nearly 105 million adults across the United States (U.S.), from 2001 through 2011. BACKGROUND: Average blood cholesterol values have declined in the U.S. since at least 1960. The National Health and Nutrition Examination Survey (NHANES) reported declining blood cholesterol values from 1999 through 2010. In the absence of more recent published data, we examined LDL-C values from a single clinical laboratory database to determine whether these values continued to decline through 2011. METHODS AND RESULTS: We extracted almost 247 million LDL-C results from nearly 105 million adults who received diagnostic testing from a single national clinical laboratory. Annual age-adjusted mean LDL-C values were calculated, and analyzed by gender. Piecewise regression analysis of the total study population indicates a breakpoint, or change in slope, in the years following 2008 (F = 163.13; p<0.05). Between 2001 and 2008, the average rate of annual decline was -2.05 mg/dL (95% CI [-2.35, -1.75]). After 2008, mean LDL-C levels flattened out, with a slope not statistically different from zero (slope = -0.10 mg/dL/year; 95% CI [-1.46, 1.26]). This stabilization was observed in both genders and all age ranges, and was also reflected in the percentage of results in low- and high-risk categories. CONCLUSIONS: The trends reported suggest historical progress in decreasing LDL-C levels, observed from 2001-2008, may have stalled in recent years. Further research is needed to determine the cause of the observed trends and develop new strategies to reduce lipid-based cardiovascular risk further.

Statins personalized.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor medications, commonly referred to as statins, are among the most widely prescribed medications. Variation in individual response to statins concerning low-density lipoprotein cholesterol reduction, clinical event benefit, and side effects has been observed. Some of this variability is attributed to demographic and environmental issues, chief of which is compliance. A large portion of the individual response to statin therapy is attributed to single nucleotide polymorphisms that have recently been elucidated, several of which seem to have clinical utility.

High-density lipoprotein subclasses and their relationship to cardiovascular disease.

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.

Genetic testing for early detection of individuals at risk of coronary heart disease and monitoring response to therapy: challenges and promises.

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient's lifetime, can help guide therapy selection, and may be of utility in family counseling.

Firefighters, heart disease, and aspects of insulin resistance: the FEMA Firefighter Heart Disease Prevention study.

OBJECTIVE: To determine the association of cardiovascular risk markers with noninvasive imaging of atherosclerosis in firefighters. METHODS: Cross-sectional investigation of subclinical atherosclerosis with metabolic, work related, and life-style variables in 296 professional firefighters. RESULTS: Calcified coronary atherosclerosis (CAC), carotid arterial intimal thickness (CIMT), and electrocardiogram provided independent CVD assessments. Homeostatic Model Assessment (HOMA) concentrations were related to heart-rate-corrected QT (QTc) (slope ± SE: 2.16 ± 65, P = 0.001), average common CIMT (0.019 ± 0.005 mm, P = 0.0005), and total CAC lesions (0.269 ± 0.116, P = 0.02). Stepwise linear regression selected fasting insulin as the strongest predictor for QTc, HOMA as the strongest predictor of average CIMT, and fasting glucose as the strongest predictor of total coronary lesion number and score. CONCLUSION: Firemen's HOMA and fasting insulin and glucose concentrations were significantly associated with three measures of CVD. Aspects of insulin resistance are related to CVD risk among firefighters.

Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy.

OBJECTIVE: To compare the effects of combination niacin extended-release + simvastatin (NER/S) versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia. PATIENTS AND METHODS: Patients (n = 137) with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4-5 weeks prior to the study) received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks) or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo) A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher's exact test. RESULTS: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B < 80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003). NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022), small LDL (55% versus 45%; P = 0.011), very low-density lipoprotein (VLDL) and total chylomicrons (63% versus 39%; P < 0.001), and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007) and VLDL (9.3% versus 0.1%; P < 0.001), compared with atorvastatin. CONCLUSION: NER/S treatment significantly improved apo A-I levels and the apo B:A-I ratio, significantly lowered the number of atherogenic LDL particles and VLDL and chylomicron particles, and increased the mean size of LDL and VLDL particles, compared with atorvastatin.

Family coronary heart disease: a call to action.

A family history of coronary heart disease (CHD) is an accepted risk factor for cardiovascular events and is independent of common CHD risk factors. Advances in the understanding of genetic influences on CHD risk provide the opportunity to apply this knowledge and improve patient care. Utility of inherited cardiovascular risk testing exists by utilizing both phenotypes and genotypes and includes improved CHD risk prediction, selection of the most appropriate treatment, prediction of outcome, and family counseling. The major impediment to widespread clinical adoption of this concept involves un-reimbursed staff time, educational needs, access to a standardized and efficient assessment mechanism, and privacy issues. The link between CHD and inheritance is indisputable and the evidence strong and consistent. For clinicians, the question is how to utilize this information, in an efficient manner, in order to improve patient care and detection of high-risk family members.

KIF6 polymorphism as a predictor of risk of coronary events and of clinical event reduction by statin therapy.

Evidence from multiple large prospective studies suggests that a common polymorphism that encodes an arginine (Arg)-to-tryptophan substitution at position 719 in the KIF6 gene is associated with coronary heart disease (CHD) and reduction in coronary events from statin therapy. Carriers of the 719Arg allele were at greater risk for primary and secondary CHD events, and statin therapy significantly reduced coronary events in 719Arg carriers but not in noncarriers. The number needed to treat to prevent a single CHD event ranged from 10 to 20 for 719Arg carriers, compared to >80 for noncarriers in the Cholesterol and Recurrent Events (CARE) study, the West of Scotland Coronary Prevention Study (WOSCOPS), the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) study. In conclusion, assessment of 719Arg carrier status holds promise for stratification of coronary event risk and for selection of optimal therapy in primary and secondary CHD prevention.