Chirag Bavishi

Purpose in Life and Its Relationship to All-Cause Mortality and Cardiovascular Events: A Meta-Analysis.

Objective To assess the net impact of purpose in life on all-cause mortality and cardiovascular events. Methods The electronic databases PubMed, Embase, and PsycINFO were systematically searched through June 2015 to identify all studies investigating the relationship between purpose in life, mortality, and cardiovascular events. Articles were selected for inclusion if, a) they were prospective, b) evaluated the association between some measure of purpose in life and all-cause mortality and/or cardiovascular events, and c) unadjusted and/or adjusted risk estimates and confidence intervals (CIs) were reported. Results Ten prospective studies with a total of 136,265 participants were included in the analysis. A significant association was observed between having a higher purpose in life and reduced all-cause mortality (adjusted pooled relative risk = 0.83 [CI = 0.75–0.91], p < .001) and cardiovascular events (adjusted pooled relative risk = 0.83 [CI = 0.75–0.92], p = .001). Subgroup analyses by study country of origin, questionnaire used to measure purpose in life, age, and whether or not participants with baseline cardiovascular disease were included in the study all yielded similar results. Conclusions Possessing a high sense of purpose in life is associated with a reduced risk for all-cause mortality and cardiovascular events. Future research should focus on mechanisms linking purpose in life to health outcomes, as well as interventions to assist individuals identified as having a low sense of purpose in life.

Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients

BACKGROUNDnThe 2014 Eighth Joint National Committee panel recommended a therapeutic target of systolic blood pressure (BP)xa0<150 mmxa0Hg in patientsxa0≥60 years of age, a departure from prior recommendation ofxa0<140 mmxa0Hg.nnnOBJECTIVESnThis study assessed the efficacy and safety of intensive BP-lowering strategies in older (agexa0≥65 years) hypertensive patients.nnnMETHODSnThe MEDLINE, Scopus, EMBASE, and Cochrane databases were searched for all relevant randomized controlled trials from 1965 through July 1, 2016. Cardiovascular (major adverse cardiovascular events [MACE], cardiovascular mortality, stroke, myocardial infarction, and heart failure), and safety (serious adverse events and renal failure) were evaluated. Random and fixed effects analysis were used to calculate pooled relative risks (RRs) andxa095% confidence intervals (CIs).nnnRESULTSnWe identified 4 high-quality trials involving 10,857 older hypertensive patients with a mean follow-up of 3.1xa0years. Intensive BP lowering was associated with a 29% reduction in MACE (RR: 0.71; 95% CI: 0.60 to 0.84), 33% in cardiovascular mortality (RR: 0.67; 95% CI: 0.45 to 0.98), and 37% in heart failure (RR: 0.63; 95% CI: 0.43 to 0.99) compared with standard BP lowering. Rates of myocardial infarction and stroke did not differ between the 2 groups. There was no significant difference in the incidence of serious adverse events (RR: 1.02; 95% CI: 0.94 to 1.09) or renal failure (RR: 1.81; 95% CI: 0.86 to 3.80) between the 2 groups. The fixed effects model yielded largely similar results, except for an increase in the risk of renal failure (RR: 2.03; 95% CI: 1.30 to 3.18) with intensive BP-lowering therapy.nnnCONCLUSIONSnIn older hypertensive patients, intensive BP control (systolic BPxa0<140 mmxa0Hg) decreased MACE, including cardiovascular mortality and heart failure. Data on adverse events were limited, but suggested an increased risk of renal failure. When considering intensive BP control, clinicians should carefully weigh benefits against potential risks.

Pre-Morbid Body Mass Index and Mortality After Incident Heart Failure: The ARIC Study

BACKGROUNDnAlthough obesity is an independent risk factor for heart failure (HF), once HF is established, obesity is associated with lower mortality. It is unclear if the weight loss due to advanced HF leads to this paradoxical finding.nnnOBJECTIVESnThis study sought to evaluate the prognostic impact of pre-morbid obesity in patients with HF.nnnMETHODSnIn the ARIC (Atherosclerosis Risk In Communities) study, we used body mass index (BMI) measured ≥6 months before incident HF (pre-morbid BMI) to evaluate the association of overweight (BMI 25 to <30 kg/m(2)) and obesity (BMI ≥30 kg/m(2)) compared with normal BMI (18.5 to <25 kg/m(2)) with mortality after incident HF.nnnRESULTSnAmong 1,487 patients with incident HF, 35% were overweight and 47% were obese by pre-morbid BMI measured 4.3 ± 3.1 years before HF diagnosis. Over 10-year follow-up after incident HF, 43% of patients died. After adjustment for demographics and comorbidities, being pre-morbidly overweight (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.58 to 0.90; p = 0.004) or obese (HR: 0.70; 95% CI: 0.56 to 0.87; p = 0.001) had a protective association with survival compared with normal BMI. The protective effect of overweight and obesity was consistent across subgroups on the basis of a history of cancer, smoking, and diabetes.nnnCONCLUSIONSnOur results, for the first time, demonstrate that patients who were overweight or obese before HF development have lower mortality after HF diagnosis compared with normal BMI patients. Thus, weight loss due to advanced HF may not completely explain the protective effect of higher BMI in HF patients.

U.S. Hospital Use of Echocardiography: Insights From the Nationwide Inpatient Sample.

BACKGROUNDnIncreased use of echocardiography (echo) raises questions of whether echo is an overused diagnostic procedure in the United States.nnnOBJECTIVESnThis study investigated national trends, practice patterns, and patient outcomes associated with inpatient echo use reported in the Nationwide Inpatient Sample (NIS).nnnMETHODSnWe identified admission diagnoses most commonly associated with echo use and performed multivariate logistic regression within each diagnosis cohort to assess whether echo use was associated with all-cause inpatient mortality. Secondary analysis was performed within our institution to validate use trends identified in the NIS database.nnnRESULTSnBetween 2001 and 2011, the absolute volume and incidence of echo steadily increased at average annual rates of 3.41% and 3.04%, respectively. In 2010, the use of echo was associated with lower odds of inpatient mortality among hospitalizations for acute myocardial infarction (adjusted odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; p < 0.001), cardiac dysrhythmia (adjusted OR: 0.72; 95% CI: 0.55 to 0.94; p = 0.02), acute cerebrovascular disease (adjusted OR: 0.36; 95% CI: 0.31 to 0.42; p < 0.001), congestive heart failure (adjusted OR: 0.82; 95% CI: 0.72 to 0.94; p = 0.005), and sepsis (adjusted OR: 0.77; 95% CI: 0.70 to 0.85; p < 0.001). In 2010, these 5 diagnoses accounted for 3.7 million hospital admissions (9% of all hospitalizations); however, echo was reported in only 8% of cases. Secondary analysis of imaging practices at our institution confirmed underuse of echo among patients who died during hospitalization for indications identified in the NIS database.nnnCONCLUSIONSnDespite increasing rates of performance, echo may be underused during critical cardiovascular hospitalizations.

Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials

Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (Valsartan/sacubitril) is a first-in-class angiotensin II-receptor neprilysin inhibitor. LCZ696 is a novel drug not only for the treatment of heart failure but it is also likely to be a useful antihypertensive drug and may have a preferential effect on systolic pressure. This review discusses (i) the mechanism of action, pharmacokinetics, and pharmacodynamics of this novel drug, (ii) the efficacy, safety, and tolerability of LCZ696 in treatment of hypertension from the available trials, (iii) evidence from other contemporary trials on combined Neprilysin inhibitors, (iv) future trials and areas of research to identify hypertensive patient populations that would most benefit from LCZ696.

Meta-Analysis of Left Ventricular Hypertrophy and Sustained Arrhythmias

Presence of left ventricular hypertrophy (LVH) has been reported to be associated with supraventricular and ventricular arrhythmias, but the association has not been systematically quantified and evaluated. A systematic search of studies in MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was undertaken through April 2014. Studies reporting on LVH and sustained arrhythmias such as atrial fibrillation and supraventricular tachycardias (SVTs) and ventricular arrhythmias (tachycardia and fibrillation) were identified. Pooled effect estimates were calculated with random-effects models (DerSimonian and Laird). A total of 10 eligible studies with 27,141 patients were included in the analysis. The incidence of SVT in patients with LVH was 11.1% compared with 1.1% among patients without LVH (p<0.001). Patients with LVH had 3.4-fold greater odds of developing SVT (odds ratio 3.39, 95% confidence interval 1.57 to 7.31) than those without LVH, although significant heterogeneity was present (I2=98%). Meta-regression analyses revealed the heterogeneity to have originated from differences in the baseline covariates such as age, male gender, hypertension, and diabetes of the individual studies. The incidence of ventricular arrhythmias was 5.5% compared with 1.2% in patients without LVH (p<0.001). The occurrence of ventricular tachycardia or fibrillation was 2.8-fold greater, in the presence of LVH (odds ratio 2.83, 95% confidence interval 1.78 to 4.51), and there was no significant heterogeneity (I2=9%). Presence of LVH in hypertensive patients is associated with a greater risk of sustained supraventricular/atrial and ventricular arrhythmias, and there is an unmet need for identifying and refining risk stratification for this group.

Prognostic Significance of Hyponatremia Among Ambulatory Patients With Heart Failure and Preserved and Reduced Ejection Fractions

Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF.

Meta-Analysis of Comparison of the Newer Oral P2Y12 Inhibitors (Prasugrel or Ticagrelor) to Clopidogrel in Patients With Non–ST-Elevation Acute Coronary Syndrome

Newer oral P2Y12 inhibitors are more potent and have faster onset of action than clopidogrel. However, the efficacy and safety in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are not well studied. A systemic search of MEDLINE and EMBASE databases was performed to identify randomized clinical trials comparing newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with NSTE-ACS. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and stroke (major cardiovascular events [MACE]). Secondary outcomes were individual components of the primary outcome, all-cause mortality, and Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding. A total of 31,470 patients with NSTE-ACS from 4 randomized clinical trials were included (newer oral P2Y12 inhibitors: 15,951; clopidogrel: 15,519). Newer oral P2Y12 inhibitors significantly decreased MACE (relative risk [RR] 0.87, 95% confidence interval [CI] 0.80 to 0.95) and MI (RR 0.85, 95% CI 0.75 to 0.96) and showed a trend toward reduction of cardiovascular death (RR 0.89, 95% CI 0.71 to 1.01). There was a significant increase in TIMI major bleeding (RR 1.27, 95% CI 1.07 to 1.50) and TIMI major or minor bleeding (RR 1.20, 95% CI 1.02 to 1.42). Results were largely similar when stratified by ticagrelor versus prasugrel (pinteraction >0.05) except for increased TIMI major/minor bleeding with prasugrel than ticagrelor (pinteractionxa0= 0.01). In conclusion, in patients with NSTE-ACS, newer oral P2Y12 inhibitors decrease MACE and MI at the expense of a significant increase in the risk of bleeding. Treatment of 1,000 patients with newer oral P2Y12 inhibitors will prevent 16 MACE and 13 MIs at the expense of increase in 6 major bleeding events.

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors.

Background— There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. Methods and Results— Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke. Odds ratio (OR) was calculated using the Mantel–Haenszel method. Subgroup analysis was done to assess the difference in safety between the smaller early-phase studies and the larger outcome studies. Our meta-analysis suggested no difference in the incidence of serious adverse events (OR, 1.00; 95% confidence interval [CI], 0.88−1.15), musculoskeletal adverse events (OR, 1.01; 95% CI, 0.87−1.13), neurocognitive adverse events (OR, 1.29; 95% CI, 0.64−2.59), or stroke (OR, 1.44; 95% CI, 0.57−3.65) with the use of PCSK9 inhibitors. Subgroup analysis of the 2 large outcome studies did suggest an increased incidence of neurocognitive adverse events (OR, 2.85; 95% CI, 1.34−6.06) with the use of PCSK9 inhibitors. However, the overall incidence of neurocognitive adverse events and stroke was <1%, whereas the cumulative incidence of serious adverse events and musculoskeletal events was >10% in both the groups. Conclusions— Our analysis suggests that PCSK9 inhibitors are not associated with an increased risk of cumulative severe adverse effects, musculoskeletal effects, or stroke. There is a signal toward adverse neurocognitive effects, seen in the outcome studies with a larger sample size and longer follow-up. There should be close monitoring, for the increased risk of neurocognitive events in the ongoing outcome studies and post-marketing surveillance.

Meta-Analysis of Radial Versus Femoral Access for Percutaneous Coronary Interventions in Non–ST-Segment Elevation Acute Coronary Syndrome

Radial access for percutaneous coronary intervention (PCI) has been shown to reduce mortality and vascular complications compared to femoral access in patients with ST-segment elevation myocardial infarction. However, efficacy and safety of radial access PCI in non-ST-segment elevation acute coronary syndrome (NSTE ACS) is not well understood. A systematic search of electronic databases was performed through July 2015 to search and identify relevant studies. We evaluated the following short-term outcomes: all-cause mortality, major bleeding, access site bleeding, and need for blood transfusions. In addition, we evaluated 1-year mortality. Studies were pooled using random effects model. Nine studies including a total of 220,126 patients (radial approach: 94,663 patients [43%], femoral approach: 125,463 patients [57%]) were included in the analysis. On pooled analysis, no significant difference in incidence of short-term all-cause mortality was found between radial and femoral access (odds ratio [OR] 0.78, 95% CI 0.57 to 1.07, p = 0.12). Radial access was associated with significant reduction in major bleeding (OR 0.52, 95% CI 0.36 to 0.73, p = 0.0002), access-site bleeding (OR 0.41, 95% CI 0.22 to 0.78, p = 0.007), and need for blood transfusions (OR 0.61, 95% CI 0.41 to 0.91, p = 0.02). Furthermore, the 1-year mortality was significantly lower in radial approach (OR 0.72, 95% CI 0.55 to 0.95, p = 0.02). In conclusion, in patients with non-ST-segment elevation acute coronary syndrome undergoing PCI, radial access is associated with decreased bleeding and access-site complications.