Treatment Of High Blood Cholesterol Research Articles

Metabolic syndrome, C-reactive protein, and mortality in U.S. Blacks and Whites: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

OBJECTIVEWe evaluate associations of metabolic syndrome (MetS), C-reactive protein (CRP), and a CRP-incorporated definition of MetS (CRPMetS) with risk of all-cause mortality in a biracial population.RESEARCH DESIGN AND METHODSWe studied 23,998 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of black and white adults ≥45 years old across the U.S. Elevated CRP was defined as ≥3 mg/L and MetS by the revised Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III; ATP III) criteria (three of five components). CRPMetS was defined as presence of three out of six components, with elevated CRP added to ATP III criteria as a sixth component. Cox models were used to calculate hazard ratios (HRs) for all-cause mortality, and population attributable risk (PAR) was calculated. Stratified analyses based on race and diabetes status were performed.RESULTSThere were 9,741 participants (41%) with MetS and 12,179 (51%) with CRPMetS at baseline. Over 4.8 years of follow-up, 2,050 participants died. After adjustment for multiple confounders, MetS, elevated CRP, and CRPMetS were each significantly associated with increased mortality risk (HRs 1.26 [95% CI 1.15–1.38], 1.55 [1.41–1.70], and 1.34 [1.22–1.48], respectively). The PAR was 9.5% for MetS, 18.1% for CRP, and 14.7% for CRPMetS. Associations of elevated CRP and of CRPMetS with mortality were significantly greater in whites than blacks, while no differences in associations were observed based on diabetes status.CONCLUSIONSBy definition, CRPMetS identifies more people at risk than MetS but still maintains a similar mortality risk. Incorporating CRP into the definition for MetS may be useful in identifying additional high-risk populations to target for prevention.

Functional impairment and Internet use among older adults: implications for meaningful use of patient portals.

Functional impairment and Internet use among older adults: implications for meaningful use of patient portals.

A current approach to statin intolerance.

Statins are the first-line pharmacotherapy for cholesterol reduction. Use of these drugs in large randomized clinical trials has consistently shown significant reductions in major vascular events, including death, myocardial infarction, stroke, and coronary revascularization. The updated guidelines for the treatment of high blood cholesterol from the American College of Cardiology/American Heart Association (ACC/AHA), will lead to an increase in the number of patients taking statins. Hence, the number of cases of statin intolerance may subsequently increase, emphasizing the need to understand and treat this important problem.

Validation of the friedewald formula in patients with metabolic syndrome.

Currently, the Friedewald formula (FF) is the main method for evaluating low-density lipoprotein cholesterol (LDL-c). Recently, many limitations have emerged regarding its use, including patients with triglyceride levels ≥400 mg/dL, diabetes mellitus, and kidney or hepatic chronic diseases. We analyzed the use of the FF in patients with metabolic syndrome. We selected patients with known metabolic syndrome that fulfilled the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report and excluded patients with triglyceride levels ≥400 mg/dL and chronic liver and/or kidney disease. Using direct assays, we measured total cholesterol, high-density lipoprotein cholesterol, triglycerides, and LDL-c. Then, LDL-c was estimated using the FF and compared with the LDL-c by direct assay. The sample size was 135 patients. Using the FF, the mean LDL-c value was 124.4 ± 42.1 mg/dL; it was 125.1 ± 38.5 mg/dL by direct assay. The correlation coefficient between these two methods was 0.89, with statistical significance (P value < 0.001). There were no significant differences between the patients with triglyceride levels >150 mg/dL (P = 0.618). In conclusion, FF is a good method for estimating LDL-c in patients with metabolic syndrome.

Preventable Coronary Heart Disease Events from Control of Cardiovascular Risk Factors in US Adults With Diabetes (Projections from Utilizing the UKPDS Risk Engine)

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal.

Low Prevalence of Metabolic Syndrome in a Group of Patients with Chronic Psychotic Disorders Taking Antipsychotic Polypharmacy in Residential Treatment While Adhering to a Mediterranean Diet

The aim of this abbreviated report is to describe the prevalence of the Metabolic Syndrome (MS) in a sample group of patients with psychosis in residential treatment in Spain, who have been treated with antipsychotic polypharmacy for 5 years or more. We designed a cross sectional study to describe the prevalence of MS in a population sample of 21 of such patients. Using the criteria recommended by the Third Report of the National Cholesterol Education program Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCP-ATP III), In this group 19, 04% of these patients met such criteria. The prevalence is much smaller than those reported in other countries, especially the U.S. This is even more remarkable, given the use of antipsychotic polypharmacy in this sample group of patients, which is an additional risk factor for the development of M.S. Residential treatment (a controlled living environment), Short Communication Forcen et al; JSRR, Article no. JSRR.2014.12.01

Association between sex hormone-binding globulin (SHBG) and metabolic syndrome among men.

Metabolic syndrome consists of a set of factors that imply increased risk of cardiovascular diseases. The objective here was to evaluate the association between sex hormone-binding globulin (SHBG), sex hormones and metabolic syndrome among men. Retrospective analysis on data from the study "Endogenous oestradiol but not testosterone is related to coronary artery disease in men", conducted in a hospital in São Paulo. Men (aged 40-70) who underwent coronary angiography were selected. The age, weight, height, waist circumference, body mass index and prevalence of dyslipidemia, hypertension and diabetes of each patient were registered. Metabolic syndrome was defined in accordance with the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII). Serum samples were collected to assess the levels of glucose, total cholesterol, HDL-cholesterol (high density lipoprotein), triglycerides, albumin, SHBG, estradiol and total testosterone (TT). The levels of LDL-cholesterol (low density lipoprotein) were calculated using Friedewald's formula and free testosterone (FT) and bioavailable testosterone (BT) using Vermeulen's formula. 141 patients were enrolled in the study. The prevalence of metabolic syndrome was significantly higher in the first SHBG tercile than in the second and third terciles. A statistically significant positive association between the SHBG and TT values was observed, but no such association was seen between SHBG, BT and FT. Low serum levels of SHBG are associated with higher prevalence of metabolic syndrome among male patients, but further studies are required to confirm this association.

Examination of the FDA Warning for Statins and Cognitive Dysfunction

Background: The ACC/AHA released new guidelines in December of 2013 for treatment of high blood cholesterol to simplify identification and treatment of patients most likely to benefit from statins. These guidelines may result in more patients receiving statin therapy, and at younger ages. In 2012, the U.S. Food and Drug Administration (FDA) mandated warnings for all statin drugs for possible adverse effects on cognitive performance. Statins can be classified as having greater lipophilic or hydrophilic solubility properties with lipophilic statins more readily crossing the blood brain barrier, and possibly differentially inducing detrimental cognitive effects. Objective: We sought to analyze generalizability of the FDA statin class warning. Methods: De-identified publicly-available data were analyzed from the FDA Adverse Event Reporting System (AERS) in relation to reports of cognitive dysfunction (primary outcome), and by type of statin (lipophilic, hydrophilic) versus “control” drugs used in the general population. Results: Significantly higher proportional reporting ratios (PRRs) were observed for lipophilic statins, which more readily cross the blood-brain barrier, (range: 1.47-3.51) compared to hydrophilic statins (range: 0.69-1.64). However, fluvastatin, lovastatin, and pitavastatin (lipophilic) had relatively few adverse reports. The signal of higher risk of cognitive dysfunction was observed for the lipophilic statin atorvastatin (PRR = 2.59, 95% confidence interval: 2.44-2.75) followed by simvastatin (PRR = 2.22, 95% confidence interval: 2.04-2.31). Hydrophilic statins (rosuvastatin, pravastatin) showed essentially no evidence suggestive of heightened risk of cognitive dysfunction. Fluvastatin, lovastatin, and pitavastatin had relatively few adverse reports, and no evidence of a higher proportion of cognitive dysfunction reports compared to the control drugs in aggregate (PRR range: 0.22 to 1.48). Conclusions: Inconsistent with the FDA class warning, highly lipophilic statins with specific pharmacokinetic properties (atorvastatin, simvastatin) appear to confer a significantly greater risk of adverse cognitive effects compared to other lipophilic statins and those with hydrophilic solubility properties.

Joint Linkage and Association Analysis with Exome Sequence Data Implicates SLC25A40 in Hypertriglyceridemia

Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50 The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …

Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation

Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption.

The Maternal Health Clinic: A New Window of Opportunity for Early Heart Disease Risk Screening and Intervention for Women with Pregnancy Complications

W cardiovascular health is a key national priority that should be addressed through improving cardiovascular awareness and prevention and reducing care inequities for women in general and younger women in particular.1–5 Given the costs of treating cardiovascular disease and screening for it, novel and innovative ways to identify women who should undergo cardiovascular risk screening, including biochemical testing, is critical to achieving this goal.

Race and the Insulin Resistance Syndrome

Type 2 diabetes remains an important cause of morbidity and mortality. The metabolic syndrome affects 25% of the adult US population based on the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults from the National Cholesterol Education Program. Knowledge on the impact of obesity on metabolic health parameters has increased greatly over the past decade. This review discusses the limitations of the National Cholesterol Education Program metabolic syndrome definition and the racial disparities in the clinical presentation of the insulin resistance syndrome. We also examine the current literature with particular emphasis on albuminuria, nonalcoholic fatty liver disease, and intramyocellular lipid content. This review explores potential environmental and genetic reasons for differences in the manifestation of insulin resistance across racial/ethnic groups and highlights several promising areas for further study.

Genistein in the Metabolic Syndrome: Results of a Randomized Clinical Trial

This study was performed to evaluate the effects of genistein on metabolic and cardiovascular risk factors in Caucasian postmenopausal subjects with metabolic syndrome (MetS). Our objective was to assess the effects of genistein on surrogate endpoints associated with diabetes and cardiovascular disease. This was a randomized, double-blind, placebo-controlled trial at 3 university medical centers in Italy. Patients included 120 postmenopausal women with MetS according to modified Third Report of the National Cholesterol Education Program (NCEP), Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. After a 4-week stabilization period, postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein daily (n = 60) for 1 year. The primary outcome was homeostasis model assessment for insulin resistance (HOMA-IR) at 1 year. Secondary outcomes were fasting glucose, fasting insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, visfatin, adiponectin, and homocysteine levels. Data on adverse events were also recorded. At 1 year in genistein recipients, fasting glucose, fasting insulin, and HOMA-IR (mean from 4.5 to 2.7; P < .001) decreased and were unchanged in placebo recipients. Genistein statistically increased HDL-C (mean from 46.4 to 56.8 mg/dL) and adiponectin and decreased total cholesterol, LDL-C (mean from 108.8 to 78.7 mg/dL), triglycerides, visfatin, and homocysteine (mean from 14.3 to 11.7 μmol/L) blood levels. Systolic and diastolic blood pressure was also reduced in genistein recipients. Genistein recipients neither experienced more side adverse effects than placebo nor discontinued the study. One year of treatment with genistein improves surrogate endpoints associated with risk for diabetes and cardiovascular disease in postmenopausal women with MetS.

Dyslipidemia and associated risk factors in a resettlement colony of Delhi

Cardiovascular diseases are a major cause of morbidity and mortality in India, with dyslipidemia contributing significantly to the risk. There are few community-based studies that highlight the burden and risk factors associated with dyslipidemia in the Indian population. To determine the prevalence and risk factors associated with dyslipidemia among adults ages 18years and older in a resettlement colony located in central Delhi. A cross-sectional study that included a random sample of 200 adults was designed. A study tool based on the World Health Organization STEPwise approach to surveillance of noncommunicable diseases and their risk factors (STEPS) questionnaire was used. Fasting venous blood sample was collected to assess the lipid profile and anthropometric measures of the participants were recorded. Criteria based on the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults were used to define the cut offs for dyslipidemia. Data were analyzed with the Statistical Package for Social Sciences, version17. Of a total of 200 study subjects, 34% had increased total cholesterol levels (≥200mg %), 38% had increased low-density lipoprotein levels (≥130mg %), 40% had increased triglyceride levels (≥150mg %), and 42% had low high-density lipoprotein levels (<40mg %). Using the logistic regression model, we found age, hypertension, alcohol consumption, and abdominal obesity to be associated with increased odds of dyslipidemia. A high proportion of individuals in the community have dyslipidemia, often associated with modifiable risk factors. The situation demands programs aimed at risk factor reduction. A focus on behavior change and health promotion targeting the younger age group is recommended.

FRI0365 Metabolic syndrome and tumor necrosis factor in childhood-onset systemic lupus erythematosus

BackgroundPatients with systemic lupus erythematosus (SLE) have a higher incidence of metabolic syndrome (MetS). Among the possible causes we may mention the inflammation associated with increased levels of triglycerides and...

FRI0129 Pro-atherogenic chemokines and TNF-alpha family cytokines in rheumatoid arthritis patients treated with atorvastatin

BackgroundCertain chemokines and TNF-α family cytokines participate in the development of atherosclerosis and in the pathogenesis of rheumatoid arthritis (RA). Early-onset and severe atherosclerosis is responsible for high incidence of...

AB0722 Prevalence of metabolic syndrome in patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by varied clinical manifestations. It mainly affects women of childbearing age and varies in intensity from a mild disease with...

Optimized Prognostic Score for Coronary Computed Tomographic Angiography: Results From the CONFIRM Registry (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry)

The aim of this study was to analyze the predictive value of coronary computed tomography angiography (CCTA) and to model and validate an optimized score for prognosis of 2-year survival on the basis of a patient population with suspected coronary artery disease (CAD). Coronary computed tomography angiography carries important prognostic information in addition to the detection of obstructive CAD. But it is still unclear how the results of CCTA should be interpreted in the context of clinical risk predictors. The analysis is based on a test sample of 17,793 patients and a validation sample of 2,506 patients, all with suspected CAD, from the international CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry. On the basis of CCTA data and clinical risk scores, an optimized score was modeled. The endpoint was all-cause mortality. During a median follow-up of 2.3 years, 347 patients died. The best CCTA parameter for prediction of mortality was the number of proximal segments with mixed or calcified plaques (C-index 0.64, p < 0.0001) and the number of proximal segments with a stenosis >50% (C-index 0.56, p = 0.002). In an optimized score including both parameters, CCTA significantly improved overall risk prediction beyond National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) score as best clinical score. According to this score, a proximal segment with either a mixed or calcified plaque or a stenosis >50% is equivalent to a 5-year increase in age or the risk of smoking. In CCTA, both plaque burden and stenosis, particularly in proximal segments, carry incremental prognostic value. A prognostic score on the basis of this data can improve risk prediction beyond clinical risk scores.

Effectiveness of a Pharmacy Care Management Program for Veterans with Dyslipidemia

To evaluate the effectiveness of a care management program provided by clinical pharmacists for veterans with dyslipidemia. Retrospective cohort design. Two primary care clinics at a Veterans Affairs Medical Center. An intervention (IT) cohort of 213 patients referred for management of dyslipidemia by clinical pharmacists and a control cohort of 219 patients with dyslipidemia receiving usual care (UC). Data were obtained from electronic medical records regarding drug therapy, lipid levels, and patient characteristics. Using multivariable regression models to adjust for baseline characteristics, the primary analyses compared mean final measured values of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TGs) among the IT and UC cohorts at the final follow-up visits. Secondary analyses compared the proportion of patients achieving National Cholesterol Education Program/Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATPIII) concordant LDL goals and the time to achieve LDL goals between the two groups. Compared with the UC cohort, the adjusted difference in the mean final measured LDL for the IT cohort was -10.4mg/dl (95% confidence interval [CI] -16.1 to -4.6, p<0.001) and TC was -12.7 (95% CI -21.3 to -4.1, p=0.004). There were no significant differences in the adjusted mean final measured HDL or TGs between the two groups. The NCEP/ATPIII goal LDL was met in 80.3% of patients in the IT cohort and 65.3% of patients in the UC cohort (odds ratio [OR], 2.6; 95% CI 1.6-4.3, p<0.001). Time to achieve goal LDL was significantly shorter for the IT cohort compared with the UC cohort (risk ratio, 1.8; 95% CI 1.2-2.8, log-rank p=0.002). Veterans referred to a clinical pharmacist for treatment of dyslipidemia achieved significant reductions in TC and LDL. A greater proportion of patients achieved NCEP/ATPIII goal LDL, and the time to attainment of LDL goals was shorter in the pharmacist-managed cohort, supporting a continued role for pharmacy care management in the treatment of patients with dyslipidemia.