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Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

BackgroundNew hypertension and heart failure guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with preserved ejection fraction (HFpEF) and hypertension be lowered to

Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with hard clinical outcomes (eg, incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed before policy recommendations. In this context, the purpose of this article is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential cotreatment with antihypertensive medications, and long lag time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, would still be at substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.

BackgroundHeart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes.ObjectivesThe purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF.MethodsOf the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort.ResultsMatched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up.ConclusionsHospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF.

BACKGROUND: Beta-blockers in high target doses are recommended for heart failure with reduced ejection fraction (HFrEF) but not for preserved ejection fraction (HFpEF). Treatment benefits are often more pronounced in high-risk subgroups, and patients with HFpEF with heart rate ≥70 beats per minute have emerged as such a high-risk subgroup. We examined the associations of high-dose beta-blocker use with outcomes in these patients. METHODS: Of the 8462 hospitalized patients with heart failure with ejection fraction ≥50% in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, 5422 had a discharge heart rate ≥70 beats per minute. Of these, 4537 had no contraindications to beta-blocker use, of which 2797 (2592 with dose data) received prescriptions for beta-blockers. Of the 2592, 730 received high-dose beta-blockers, defined as atenolol ≥100 mg/day, carvedilol ≥50 mg/day, metoprolol tartrate or succinate ≥200 mg/day, or bisoprolol ≥10 mg/day, and 1740 received no beta-blockers. Using propensity scores for the receipt of high-dose beta-blockers, we assembled a matched cohort of 1280 patients, balanced on 58 characteristics. RESULTS: All-cause mortality occurred in 63% and 68% of matched patients receiving high-dose beta-blocker vs no beta-blocker, respectively, during 6 years (median, 2.8) of follow-up (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P = .027). The hazard ratios (95% confidence intervals) for all-cause readmission and the combined endpoint of all-cause readmission or all-cause mortality associated with high-dose beta-blocker use were 0.90 (0.81-1.02) and 0.89 (0.80-1.00), respectively. CONCLUSIONS: In patients with HFpEF and heart rate ≥70 beats per minute, high-dose beta-blocker use was associated with a significantly lower risk of death. Future randomized controlled trials are needed to examine this association.

ObjectivesWe evaluated trends in hypertension prevalence, awareness, treatment and control in an Indian urban population over 25 years. Trends were projected to year 2030 to determine attainment of World Health Organization (WHO) Global Monitoring Framework targets.MethodsAdult participants (n=7440, men 4237, women 3203) enrolled in successive population based studies in Jaipur, India from years 1991 to 2015 were evaluated for hypertension prevalence, awareness, treatment and control. The studies were performed in years 1991-93 (n=2212), 1999-01 (n=1123), 2003-04 (n=458), 2006-07 (n=1127), 2009-10 (n=739) and 2012-15 (n=1781). Descriptive statistics are reported. We used logarithmic forecasting to year 2030 and compared outcomes to WHO target of 25% lower prevalence and >50% control.ResultsThe age-adjusted hypertension prevalence (%) among adults in successive studies increased from 29.5, 30.2, 36.5, 42.1, 34.4 to 36.1 (R2=0.41). Increasing trends were observed for hypertension awareness (13, 44, 49, 44, 49, 56; R2=0.63); treatment in all (9, 22, 38, 34, 41, 36; R2=0.68) and aware hypertensives (61, 66, 77, 79, 70, 64; R2=0.46); and control in all (2, 14, 13, 18, 21, 21; R2=0.82), aware (12, 33, 27, 46, 37, 37; R2=0.54) and treated (9, 20, 21, 48, 36, 49; R2=0.80) hypertensive participants. Projections to year 2030 show increases in prevalence to 44% (95% CI 43-45), awareness to 82% (81-83), treatment to 62% (61-63), and control to 36% (35-37).ConclusionHypertension prevalence, awareness, treatment and control rates are increasing among urban populations in India. Better awareness is associated with greater control. The rates of increase are off-target for WHO Global Monitoring Framework and UN Sustainable Development Goals.

See Article by White et al .

AimsTo examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial.Methods and resultsTwo thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695).ConclusionIn patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many patients. This meta-analysis of seven randomized, double-blind studies (N = 5888) evaluated 8 weeks of olmesartan medoxomil (OM)-based single-pill dual-combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM monotherapy in adults with hypertension. BP-lowering efficacy, goal achievement, and adverse events were assessed in the full cohort and subgroups (elderly/nonelderly and patients with and without chronic kidney disease). In the full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP and BP goal achievement (

BackgroundA lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF).ObjectivesThe aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF.MethodsOf the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of

BackgroundDigoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF.MethodsOf the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models.ResultsMatched patients (n = 316) had a mean age of 83 years, 74% were women, and 18% African American. Thirty-day all-cause readmission occurred in 21% and 20% of patients receiving and not receiving digoxin, respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all-cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI, 0.38-2.12), or a combined endpoint of all-cause readmission or all-cause mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained unchanged at 1 year postdischarge.ConclusionsThe lack of an association between digoxin and 30-day all-cause readmission in older nursing home residents hospitalized for HF is intriguing and needs to be interpreted with caution given the small sample size.

BackgroundIsolated systolic hypertension and isolated diastolic hypotension are common in older adults and associated with a higher risk of incident heart failure (HF). However, little is known about the prevalence and impact of isolated diastolic hypertension in this population.MethodsIn the Cardiovascular Health Study (CHS), of the 5776 community-dwelling older adults ≥65years who had data on baseline systolic and diastolic blood pressure (SBP and DBP), 28 had isolated diastolic hypertension (DBP ≥90mmHg and SBP

BackgroundIsolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults.MethodsIn the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP

BackgroundTherapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF).MethodsWe examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤2.5 for men and ≤2mg/dl for women, and serum potassium

BackgroundHeart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure.MethodsOf the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American).ResultsDuring 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P

BackgroundHeart failure is the leading cause for 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. There is a growing interest in understanding the impact of evidence-based heart failure therapy on 30-day all-cause readmission. In the current study, we examined the impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI-ARBs) on 30-day all-cause readmission in heart failure.MethodsOf the 1384 hospitalized Medicare beneficiaries with heart failure and left ventricular ejection fraction

BackgroundImprovement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65-85 years) with or without chronic kidney disease (CKD).MethodsPatients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR 3 times the upper limit of normal occurred in 4.4% of atorvastatin- and 0.2% of pravastatin-treated patients.ConclusionIntensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA.

Cardiovascular morbidity and mortality as a result of inhaled tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations lacking the infrastructure to develop and implement effective public health policies limiting tobacco use. Following initiation of public awareness campaigns 50 years ago in the United States, considerable success has been achieved in reducing the prevalence of cigarette smoking and exposure to secondhand smoke. However, there has been a slowing of cessation rates in the United States during recent years, possibly caused by high residual addiction or fatigue from cessation messaging. Furthermore, tobacco products have continued to evolve faster than the scientific understanding of their biological effects. This review considers selected updates on the genetics and epigenetics of smoking behavior and associated cardiovascular risk, mechanisms of atherogenesis and thrombosis, clinical effects of smoking and benefits of cessation, and potential impact of electronic cigarettes on cardiovascular health.

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.

BackgroundBeta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act.MethodsOf the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction

BackgroundAccording to the 2004 Surgeon General's Report on Health Consequences of Smoking, after >15 years of abstinence, the cardiovascular risk of former smokers becomes similar to that of never-smokers. Whether this health benefit of smoking cessation varies by amount and duration of prior smoking remains unclear.Methods and resultsOf the 4482 adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study, 2556 were never-smokers, 629 current smokers, and 1297 former smokers with >15 years of cessation, of whom 312 were heavy smokers (highest quartile; ≥32 pack-years). Age-sex-race-adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for centrally adjudicated incident HF and mortality during 13 years of follow-up were estimated using Cox regression models. Compared with never-smokers, former smokers as a group had similar risk for incident HF (aHR, 0.99; 95% CI, 0.85-1.16) and all-cause mortality (aHR, 1.08; 95% CI, 0.96-1.20), but former heavy smokers had higher risk for both HF (aHR, 1.45; 95% CI, 1.15-1.83) and mortality (aHR, 1.38; 95% CI, 1.17-1.64). However, when compared with current smokers, former heavy smokers had lower risk of death (aHR, 0.64; 95% CI, 0.53-0.77), but not of HF (aHR, 0.97; 95% CI, 0.74-1.28).ConclusionsAfter >15 years of smoking cessation, the risk of HF and death for most former smokers becomes similar to that of never-smokers. Although this benefit of smoking cessation is not extended to those with ≥32 pack-years of prior smoking, they have lower risk of death relative to current smokers.

BackgroundCharacteristics and outcomes of patients with heart failure and reduced ejection fraction receiving care at Veterans Affairs (VA) versus non-VA hospitals have not been previously reported.Methods and resultsIn the randomized controlled Beta-blocker Evaluation of Survival Trial (BEST; 1995-1999), of the 2707 (bucindolol=1353; placebo=1354) patients with heart failure and left ventricular ejection fraction ≤35%, 918 received care at VA hospitals, of which 98% (n=898) were male. Of the 1789 receiving care at non-VA hospitals, 68% (n=1216) were male. Our analyses were restricted to these 2114 male patients. VA patients were older with higher symptom and comorbidity burdens. There was no significant between-group difference in unadjusted primary end point of 2-year all-cause mortality (35% VA versus 32% non-VA; hazard ratio associated with VA hospitals, 1.09; 95% confidence interval, 0.94-1.26), which remained unchanged after adjustment for age and race (hazard ratio, 1.00; 95% confidence interval, 0.86-1.16) or multivariable adjustment, including cardiovascular morbidities (hazard ratio, 0.94; 95% confidence interval, 0.80-1.10). There was no between-group difference in cause-specific mortalities or hospitalizations. Chronic kidney disease, pulmonary edema, left ventricular ejection fraction

BackgroundLittle is known about associations of calcium channel blockers (CCBs) with outcomes in patients with heart failure and preserved ejection fraction (EF).Methods and resultsOf the 10 570 hospitalized patients with heart failure and preserved EF, ≥65 years, EF ≥40%, in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF; 2003-2004), linked to Medicare data (through December 31, 2008), 7514 had no prior history of CCB use. Of these, 815 (11%) patients received new discharge prescriptions for CCBs. Propensity scores for CCB initiation, calculated for each of the 7514 patients, were used to assemble a matched cohort of 1620 (810 pairs) patients (mean age, 80 years; mean EF, 56%; 65% women; 10% black) receiving and not receiving CCBs, balanced on 114 baseline characteristics. The primary composite end point of all-cause mortality or heart failure hospitalization occurred in 82% and 81% of patients receiving and not receiving CCBs (hazard ratio for CCBs, 1.03; 95% confidence interval, 0.92-1.14). Hazard ratios (95% confidence intervals) for all-cause mortality, heart failure hospitalization, and all-cause hospitalization were 1.05 (0.94-1.18), 1.05 (0.91-1.21), and 1.03 (0.93-1.14), respectively. Similar associations were observed when we categorized patients into those receiving amlodipine and nonamlodipine CCBs. Among 7514 prematch patients, multivariable-adjusted and propensity-adjusted hazard ratios (95% confidence interval) for primary composite end point were 1.03 (0.95-1.12) and 1.02 (0.94-1.11), respectively.ConclusionsIn hospitalized older patients with heart failure, new discharge prescriptions for CCBs had no associations with composite or individual end points of mortality or heart failure hospitalization, regardless of the class of CCBs.

Although randomized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction (HFrEF), they excluded patients with serum creatinine >2.5 mg/dl, and their use is contraindicated in those with advanced chronic kidney disease (CKD). In the present analysis, we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD. Of the 1,140 patients with HFrEF (EF

ObjectiveTo determine levels of cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians.MethodsPopulation based 6123 subjects (men 3388) were evaluated. Mean±1SD of various cholesterol lipoproteins (total, HDL, LDL and non-HDL cholesterol) and triglycerides were reported. Subjects were classified according to US National Cholesterol Education Program.ResultsAge-adjusted levels in men and women were cholesterol total 178.4 ± 39 and 184.6 ± 39, HDL 44.9 ± 11 and 51.1 ± 11, LDL 102.5 ± 33 and 106.2 ± 33, total:HDL 4.15 ± 1.2 and 3.79 ± 1.0 and triglycerides 162.5 ± 83 and 143.7 ± 83 mg/dl. Age-adjusted prevalence (%) in men and women, respectively were, total cholesterol ≥200 mg/dl 25.1 and 24.9, LDL cholesterol ≥130 mg/dl 16.3 and 15.1 and ≥100 mg/dl 49.5 and 49.7, HDL cholesterol

BackgroundHeart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.MethodsOf the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.ResultsThirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction

UnlabelledSeveral plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P ≤ 0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.Trial registrationClinicalTrials.gov NCT00327691.

BackgroundWhether prediabetes is an independent risk factor for incident heart failure (HF) in non-diabetic older adults remains unclear.MethodsOf the 4602 Cardiovascular Health Study participants, age≥65 years, without baseline HF and diabetes, 2157 had prediabetes, defined as fasting plasma glucose (FPG) 100-125 mg/dL. Propensity scores for prediabetes, estimated for each of the 4602 participants, were used to assemble a cohort of 1421 pairs of individuals with and without prediabetes, balanced on 44 baseline characteristics.ResultsParticipants had a mean age of 73 years, 57% were women, and 13% African American. Incident HF occurred in 18% and 20% of matched participants with and without prediabetes, respectively (hazard ratio {HR} associated with prediabetes, 0.90; 95% confidence interval {CI}, 0.76-1.07; p=0.239). Unadjusted and multivariable-adjusted HRs (95% CIs) for incident HF associated with prediabetes among 4602 pre-match participants were 1.22 (95% CI, 1.07-1.40; p=0.003) and 0.98 (95% CI, 0.85-1.14; p=0.826), respectively. Among matched individuals, prediabetes had no independent association with incident acute myocardial infarction (HR, 1.02; 95% CI, 0.81-1.28; p=0.875), angina pectoris (HR, 0.93; 95% CI, 0.77-1.12; p=0.451), stroke (HR, 0.86; 95% CI, 0.70-1.06; p=0.151) or all-cause mortality (HR, 0.99; 95% CI, 0.88-1.11; p=0.840).ConclusionsWe found no evidence that prediabetes is an independent risk factor for incident HF, other cardiovascular events or mortality in community-dwelling older adults. These findings question the wisdom of routine screening for prediabetes in older adults and targeted interventions to prevent adverse outcomes in older adults with prediabetes.

In this multicenter trial, the effects of nebivolol added to an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) were assessed in patients with hypertension (diastolic blood pressure [DBP] 80-110 mm Hg) and prediabetes (fasting blood glucose 100-125 mg/dL and/or 2-hour oral glucose tolerance test [OGTT] 140-199 mg/dL). After a 4-week run-in period (in which lisinopril [10 mg/d] or losartan [50 mg/d] treatment was initiated), patients with DBP 90-110 mm Hg were randomized (2:2:1) to 12-week, double-blind treatment with nebivolol (n=223; 5-40 mg/d), hydrochlorothiazide (HCTZ; n=212; 12.5-25 mg/d), or placebo (n=102), titrated to achievement of 130/80 mm Hg. The primary outcome measure was DBP (last observation carried forward, intent to treat population); secondary measures included systolic blood pressure (SBP) and glucose levels. At baseline, overall mean values for body mass index, triglycerides, and high-density lipoprotein cholesterol were 32.3 kg/m(2) , 1.7 mmol/L, and 1.3 mmol/L, respectively. At week 12, nebivolol and placebo groups demonstrated a decrease of -9.4 and -5.0 mm Hg, respectively (P

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD.

Residual coronary heart disease remains a significant problem even after adequate statin therapy for cardiovascular risk reduction as currently recommended by the Adult Treatment Panel III (ATP-III) of the National Cholesterol Education Program (NCEP). This is particularly true for the high risk patients as defined by ATP-III that includes those patients who have a greater than 20% 10-year risk of adverse cardiac events. For such patients the current goal of a low-density lipoprotein cholesterol (LDL-cholesterol) maintenance level of < or =100 mg/dL plasma appears to be suboptimal. Accumulating data from several recent randomized studies of more aggressive LDL-cholesterol reduction to levels below 70 mg/dL in the high risk patients favor acceptance of such a new lower target for LDL-cholesterol using more intensive statin therapy which would affect the treatment strategy for patients with coronary heart disease pre-percutaneous intervention, metabolic syndrome, diabetes mellitus, congestive heart failure, cerebrovascular disease and chronic kidney disease.

ObjectiveTo determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India.MethodsPhysicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported.ResultsWe evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care.ConclusionsThere is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India.