Targeting mulitple dyslipidemias with fixed combinations – focus on extended release niacin and simvastatin

Dyslipidemia is a major risk factor in the initiation and progression of cardiovascular diseases such as atherosclerosis. Several pharmacological agents have been developed over the past 50 years which target various lipid components such as low density lipoprotein (LDL) cholesterol, triglyceride, and high density lipoprotein (HDL) cholesterol. Similar to other risk factors such as hypertension and diabetes mellitus, the management of dyslipidemia can be complicated and may require combination therapy for effective treatment. This review discusses the biochemical mechanisms of action and clinical uses for simvastatin (the most widely available and commercially prescribed statin) and niacin, and the combination of these agents in the management and treatment of dyslipidemia

Lifestyle Risk Factors and Cardiovascular Disease in Cubans and Cuban Americans

Cardiovascular disease is the leading cause of mortality in Cuba. Lifestyle risk factors for coronary heart disease (CHD) in Cubans have not been compared to risk factors in Cuban Americans. Articles spanning the last 20 years were reviewed. The data on Cuban Americans are largely based on the Hispanic Health and Nutrition Examination Survey (HHANES), 1982–1984, while more recent data on epidemiological trends in Cuba are available. The prevalence of obesity and type 2 diabetes mellitus remains greater in Cuban Americans than in Cubans. However, dietary preferences, low physical activity, and tobacco use are contributing to the rising rates of obesity, type 2 diabetes mellitus, and CHD in Cuba, putting Cubans at increased cardiovascular risk. Comprehensive national strategies for cardiovascular prevention that address these modifiable lifestyle risk factors are necessary to address the increasing threat to public health in Cuba

Everything in Moderation: Investigating the U-Shaped Link Between HDL Cholesterol and Adverse Outcomes

Despite historical evidence suggesting an inverse association between HDL cholesterol (HDL-C) and adverse cardiovascular events, pharmacological efforts to increase HDL-C and improve outcomes have not been successful. Recently, a U-shaped association between HDL-C and adverse events has been demonstrated in several population cohorts, further complicating our understanding of the clinical significance of HDL. Potential explanations for this finding include genetic mutations linked to very high HDL-C, impaired HDL function at high HDL-C levels, and residual confounding. However, our understanding of this association remains premature and needs further investigation

Tracking Cardiac Rehabilitation Utilization in Medicare Beneficiaries: 2017 UPDATE

PURPOSE: This study updates cardiac rehabilitation (CR) utilization data in a cohort of Medicare beneficiaries hospitalized for CR-eligible events in 2017, including stratification by select patient demographics and state of residence. METHODS: We identified Medicare fee-for-service beneficiaries who experienced a CR-eligible event and assessed their CR participation (≥1 CR sessions in 365 d), engagement, and completion (≥36 sessions) rates through September 7, 2019. Measures were assessed overall, by beneficiary characteristics and state of residence, and by primary (myocardial infarction; coronary artery bypass surgery; heart valve repair/replacement; percutaneous coronary intervention; or heart/heart-lung transplant) and secondary (angina; heart failure) qualifying event type. RESULTS: In 2017, 412 080 Medicare beneficiaries had a primary CR-eligible event and 28.6% completed ≥1 session of CR within 365 d after discharge from a qualifying event. Among beneficiaries who completed ≥1 CR session, the mean total number of sessions was 25 ± 12 and 27.6% completed ≥36 sessions. Nebraska had the highest enrollment rate (56.1%), with four other states also achieving an enrollment rate \u3e50% and 23 states falling below the overall rate for the United States. CONCLUSIONS: The absolute enrollment, engagement, and program completion rates remain low among Medicare beneficiaries, indicating that many patients did not benefit or fully benefit from a class I guideline-recommended therapy. Additional research and continued widespread adoption of successful enrollment and engagement initiatives are needed, especially among identified populations

Oxidative Stress is Associated with Increased Pulmonary Artery Systolic Pressure in Humans

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine; glutathione, and its oxidized disulphide (GSSG) were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/GSSG couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (p\u3c0.001), gender (p=0.002), mitral regurgitation (p\u3c0.001), left ventricular ejection fraction (p\u3c0.001), left atrial size (p\u3c 0.001), diabetes (p=0.03), Plasma Ln cystine (β=9.53, p\u3c0.001), Ln glutathione (β =-5.4, p=0.002), and Eh glutathione (β =0.21, p=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56, p=0.007), mitral regurgitation (β= 4.52, P\u3c0.001), statin use (β =-3.39, p=0.03), left ventricular ejection fraction (β=-0.26, p=0.003), and age (β=0.17, p=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study

Using metabolic equivalents in clinical practice

Metabolic equivalents, or METs, are routinely employed as a guide to exercise training and activity prescription and to categorize cardiorespiratory fitness (CRF). There are, however, inherent limitations to the concept, as well as common misapplications. CRF and the patient's capacity for physical activity are often overestimated and underestimated, respectively. Moreover, frequently cited fitness thresholds associated with the highest and lowest mortality rates may be misleading, as these are influenced by several factors, including age and gender. The conventional assumption that 1 MET = 3.5 mL O-2/kg/min has been challenged in numerous studies that indicate a significant overestimation of actual resting energy expenditure in some populations, including coronary patients, the morbidly obese, and individuals taking beta-blockers. These data have implications for classifying relative energy expenditure at submaximal and peak exercise. Heart rate may be used to approximate activity METs, resulting in a promising new fitness metric termed the "personal activity intelligence" or PAI score. Despite some limitations, the MET concept provides a useful method to quantitate CRF and define a repertoire of physical activities that are likely to be safe and therapeutic. In conclusion, for previously inactive adults, moderate-to vigorous physical activity, which corresponds to >= 3 METs, may increase MET capacity and decrease the risk of future cardiac events. (C) 2017 Elsevier Inc. All rights reserved

Response to letter regarding article by Patel et al: A Novel Biomarker of Oxidative Stress is Associated with Risk of Death in Patients with Coronary Artery Disease

We thank Drs Giral and colleagues for their interest in our work.1 They raise the important query of whether our findings would still persist after adjustment for γ-glutamyltransferase (GGT), given that GGT activity hydrolyzes glutathione (GSH) to produce glutamate+cysteinylglycine. This point, however, is not relevant to our description of GSH/cystine as a useful biomarker of cardiovascular disease, because our samples were all collected with a preservation solution containing a GGT

Aggregate Risk Score Based on Markers of Inflammation, Cell Stress, and Coagulation Is an Independent Predictor of Adverse Cardiovascular Outcomes

Objectives: This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI). Background Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways - high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels - would be a powerful predictor of death and MI. Methods: Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. Results: Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score. Conclusions: An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD

A Novel Biomarker of Oxidative Stress is Associated with Risk of Death in Patients with Coronary Artery Disease

Background—Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes. Methods and Results—Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p\u3c0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (\u3e+1 SD & \u3c-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. Conclusions—A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress