[Show abstract][Hide abstract] ABSTRACT: The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has recently released the new cholesterol treatment guideline. This update was based on a systematic review of the evidence and replaces the previous guidelines from 2002 that were widely accepted and implemented in clinical practice. The new cholesterol treatment guideline emphasizes matching the intensity of statin treatment to the level of atherosclerotic cardiovascular disease (ASCVD) risk and replaces the old paradigm of pursuing low-density lipoprotein cholesterol targets. The new guideline also emphasizes the primacy of the evidence base for statin therapy for ASCVD risk reduction and lists several patient groups that will not benefit from statin treatment despite their high cardiovascular risk, such as those with heart failure (New York Heart Association class II-IV) and patients undergoing hemodialysis. The guideline has been received with mixed reviews and significant controversy. Because of the evidence-based nature of the guideline, there is room for several questions and uncertainties on when and how to use lipid-lowering therapy in clinical practice. The goal of the Mayo Clinic Task Force in the assessment, interpretation, and expansion of the ACC/AHA cholesterol treatment guideline is to address gaps in information and some of the controversial aspects of the newly released cholesterol management guideline using additional sources of evidence and expert opinion as needed to guide clinicians on key aspects of ASCVD risk reduction.
Mayo Clinic Proceedings 08/2014; 89(9). DOI:10.1016/j.mayocp.2014.06.016 · 6.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130246.
JAMA The Journal of the American Medical Association 11/2013; 311(3). DOI:10.1001/jama.2013.282836 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stent thrombosis (ST) is a rare but life-threatening complication of coronary artery stenting. Although dual-antiplatelet therapy is an effective management strategy in reducing the risk for ST, some patients may need to interrupt their regimens because of unforeseen circumstances, such as the requirement for surgery. In conclusion, this case presentation highlights some pertinent issues related to ST, including its risk factors, the perioperative management of antiplatelet agents, and treatment for ST.
The American journal of cardiology 07/2013; 112(7). DOI:10.1016/j.amjcard.2013.05.041 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To highlight the recent data evaluating pharmacological manipulation of HDL cholesterol (HDL-C) and examine whether medication-induced changes were associated with improved clinical outcomes and reduced short-term and long-term cardiovascular risks. The review focuses on the studies with niacin and the new cholesteryl ester transfer protein (CETP) inhibitors torcetrapib, dalcetrapib, anacetrapib and evacetrapib.
Several large randomized clinical trials have evaluated drug therapy on HDL-C and cardiovascular outcomes. Two studies have evaluated the clinical outcomes following HDL-C raising with niacin. Data from the Heart Protection 2 Treatment of HDL to Reduce the Incidence of Vascular Events and The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health trials both demonstrated no clinical benefit from use of niacin therapy when added to background statin therapy with regard to short-term and long-term cardiovascular risk reduction. Both studies demonstrated excess side-effects from use of niacin. A number of clinical trials have evaluated HDL-C modification from use of a CETP inhibitor. All of the studies have demonstrated significant increases in HDL-C. To date, the outcome data are not favorable. Use of torcetrapib was associated with excess mortality. Use of dalcetrapib had no effect on short-term and long-term cardiovascular events. Two outcome studies with anacetrapib and evacetrapib are ongoing and will report out in a few years' time.
Pharmacological manipulation of HDL-C has not improved the cardiovascular outcomes. Several agents have caused harm or unacceptable side-effects. Further studies are needed before one can recommend the use of additional lipid-modifying therapies beyond statins.
Current opinion in cardiology 07/2013; 28(4):389-98. DOI:10.1097/HCO.0b013e328362059d · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA). BACKGROUND: Risk stratification for SCD, a major cause of mortality, is difficult. OSA is linked to cardiovascular disease and arrhythmias, and has been shown to increase the risk of nocturnal SCD. It is unknown if OSA independently increases the risk of SCD. METHODS: We included 10,701 consecutive adults undergoing their first diagnostic polysomnogram between 7/1987 and 7/2003. During follow-up up to 15 years, we assessed incident resuscitated or fatal SCD in relationship to the presence of OSA, physiological data including the apnea-hypopnea index (AHI) and nocturnal oxygen saturation (O2sat) parameters, and relevant comorbidities. RESULTS: During an average follow-up of 5.3 years, 142 patients had resuscitated or fatal SCD (annual rate 0.27%). In multivariate analysis, independent risk factors for SCD were age, hypertension, coronary artery disease, cardiomyopathy or heart failure, ventricular ectopy or nonsustained ventricular tachycardia, and lowest nocturnal O2sat (per -10%, HR 1.14, P=0.029). SCD was best predicted by age >60 years (HR 5.53), AHI >20 (HR 1.60), mean nocturnal O2sat <93% (HR 2.93), and lowest nocturnal O2sat <78% (HR 2.60, all P<0.0001). CONCLUSIONS: In a population of 10,701 adults referred for polysomnography, OSA predicted incident SCD, and the magnitude of risk was predicted by multiple parameters characterizing OSA severity. Nocturnal hypoxemia, an important pathophysiological feature of OSA, strongly predicted SCD independently of well-established risk factors. These findings implicate OSA, a prevalent condition, as a novel risk factor for SCD.
Journal of the American College of Cardiology 06/2013; 62(7). DOI:10.1016/j.jacc.2013.04.080 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.
METHODS: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.
RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons).
CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.).
New England Journal of Medicine 11/2012; 367(22). DOI:10.1056/NEJMoa1206797 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical trials of cardiovascular disease (CVD) prevention in patients with type 2 diabetes mellitus primarily have been directed at the modification of a single major risk factor; however, in trials that enroll patients with and without diabetes, the absolute risk in CVD events remains higher in patients with diabetes. Efforts to reduce the macrovascular and microvascular residual risk have been directed toward a multifactorial CVD risk-factor modification; nonetheless, long-term complications remain high. Dual-peroxisome proliferator-activated receptor (PPAR) α/γ agonists may offer opportunities to lower macrovascular and microvascular complications of type 2 diabetes mellitus beyond the reductions achieved with conventional risk-factor modification. The information presented elucidates the differentiation of compound-specific vs class-effect properties of PPARs as the basis for future development of a new candidate molecule. Prior experience with thiazolidinediones, an approved class of PPARγ agonists, and glitazars, investigational class of dual-PPARα/γ agonists, also provides important lessons about the risks and benefits of targeting a nuclear receptor while revealing some of the future challenges for regulatory approval.
American heart journal 11/2012; 164(5):672-80. DOI:10.1016/j.ahj.2012.06.023 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Patterns of clinical symptoms and outcomes of perioperative myocardial infarction (PMI) in elderly patients after hip fracture repair surgery are not well defined.
A retrospective 1:2 case-control study in a cohort of 1212 elderly patients undergoing hip fracture surgery from 1988 to 2002 in Olmsted County, Minnesota.
The mean age was 85.3 ± 7.4 years; 76% female. PMI occurred in 167 (13.8%) patients within 7 days, of which 153 (92%) occurred in first 48 hours; 75% of patients were asymptomatic. Among patients with PMI, in-hospital mortality was 14.4%, 30-day mortality was 29 (17.4%), and 1-year mortality was 66 (39.5%). PMI was associated with a higher inpatient mortality rate (odds ratio [OR], 15.1; confidence interval [CI], 4.6-48.8), 30-day mortality (hazard ratio [HR], 4.3; CI, 2.1-8.9), and 1-year mortality (HR, 1.9; CI, 1.4-2.7).
Elderly patients, after hip fracture surgery, have a higher incidence of PMI and mortality than what guidelines indicate. The majority of elderly patients with PMI did not experience ischemic symptoms and required cardiac biomarkers for diagnosis. The results of our study support the measurement of troponin in postoperative elderly patients for the diagnosis of PMI, in order to implement in-hospital preventive strategies to reduce PMI-associated mortality.
Journal of Hospital Medicine 11/2012; 7(9). DOI:10.1002/jhm.1967 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We sought to determine whether persons with intermediate risk factors for cardiovascular disease presenting to an emergency department with chest pain and chronic kidney disease (CKD) were triaged effectively by chest pain units (CPUs). CPUs evaluate patients with intermediate risk and acute chest pain effectively. CKD is a risk factor for poor outcomes once cardiovascular disease has developed. However, current algorithms to risk stratify patients with acute chest pain do not include renal function. A total of 408 patients enrolled previously in the CHEER study of intermediate risk patients with chest pain, assigned randomly to hospitalization or observation in a CPU where an estimated glomerular filtration rate (GFR) was available, were included. No difference was found in short-term outcomes of patients including in-hospital death, myocardial infarction, or coronary revascularization based on renal function. For the 205 patients randomized to the CPU, the rate of admission to the hospital was significantly higher in the group with CKD compared with the group with normal renal function (68.2 vs 48.2%, P=0.007). In a multivariate analysis, decreased renal function was not associated with adverse short-term outcomes. On 5 years follow-up, the overall long-term mortality was significantly higher in the group with CKD (14.1% vs 5.5%, P=0.003). We concluded that CKD is a strong predictor of hospitalization and overall long-term mortality in patients presenting with chest pain to the emergency department. Current risk factor stratification scoring systems should consider CKD as a predictor of increased risk in patients with chest pain.
[Show abstract][Hide abstract] ABSTRACT: Evidence suggests that metabolic syndrome (MbS) is associated with early senescence of bioprosthetic aortic valve prostheses. The purpose of this study was to determine whether MbS is also associated with accelerated failure of bioprosthetic valves prostheses in the mitral position.
Records of all patients undergoing bioprosthetic mitral valve replacement (MVR) from 1993 to 2000 were reviewed.
Of 114 patients undergoing bioprosthetic MVR, 48 (42%) had MbS. Mean age was 73 years (vs. 74 years for no MbS). Patients underwent MVR for regurgitation (n = 97; 85%), stenosis (n = 12; 11%), or mixed lesions (n = 4; 4%). Etiology was degenerative (n = 35; 32%), rheumatic (n = 26; 24%), ischemic (n = 30; 28%), calcific (n = 9; 8%), and endocarditis (n = 8; 8%). Mean follow-up was 4.5 years. Overall survival at 5 and 10 years was 56% and 26%, respectively. Survival was similar between groups (p = 0.15). Five patients (2 MbS; 4% vs. 3 no MbS; 5%) required mitral reoperation at a mean of 3.8 years after initial MVR. The risk of prosthetic valve failure was not different between groups (p = 0.66). Despite no initial difference in transmitral gradients, gradients beyond five-year follow-up were greater for those with MbS (6.8 mmHg MbS vs. 4.7 mmHg no MbS, p = 0.007). Independent predictors of gradient progression beyond two years were MbS (p = 0.027) and female gender (p = 0.012). There were no significant differences in valve area, regurgitation, or ejection fraction.
Although overall survival following bioprosthetic MVR is challenging, MbS did not predict diminished survival or excess reoperative risk compared to non-MbS patients. The trend toward more rapid progression of transprosthetic gradients in MbS patients warrants further investigation.
Journal of Cardiac Surgery 03/2012; 27(2):146-51. DOI:10.1111/j.1540-8191.2011.01412.x · 0.89 Impact Factor