Abigail S. Baldridge

Global cardiovascular research output, citations, and collaborations: A time-trend, bibliometric analysis (1999-2008)

Introduction Health research is one mechanism to improve population-level health and should generally match the health needs of populations. However, there have been limited data to assess the trends in national-level cardiovascular research output, even as cardiovascular disease [CVD] has become the leading cause of morbidity and mortality worldwide. Materials and Methods We performed a time trends analysis of cardiovascular research publications (1999–2008) downloaded from Web of Knowledge using a iteratively-tested cardiovascular bibliometric filter with >90% precision and recall. We evaluated cardiovascular research publications, five-year running actual citation indices [ACIs], and degree of international collaboration measured through the ratio of the fractional count of addresses from one country against all addresses for each publication. Results and Discussion Global cardiovascular publication volume increased from 40 661 publications in 1999 to 55 284 publications in 2008, which represents a 36% increase. The proportion of cardiovascular publications from high-income, Organization for Economic Cooperation and Development [OECD] countries declined from 93% to 84% of the total share over the study period. High-income, OECD countries generally had higher fractional counts, which suggest less international collaboration, than lower income countries from 1999–2008. There was an inverse relationship between cardiovascular publications and age-standardized CVD morbidity and mortality rates, but a direct, curvilinear relationship between cardiovascular publications and Human Development Index from 1999–2008. Conclusions Cardiovascular health research output has increased substantially in the past decade, with a greater share of citations being published from low- and middle-income countries. However, low- and middle-income countries with the higher burdens of cardiovascular disease continue to have lower research output than high-income countries, and thus require targeted research investments to improve cardiovascular health.

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

Background—Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular or right ventricular longitudinal strain. Methods and Results—We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15–2.07; P=0.006). Conclusions—Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF. Registration Information—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.

Proteomic profiling of a robust Wolbachia infection in an Aedes albopictus mosquito cell line

Wolbachia pipientis, a widespread vertically transmitted intracellular bacterium, provides a tool for insect control through manipulation of host–microbe interactions. We report proteomic characterization of wStr, a Wolbachia strain associated with a strong cytoplasmic incompatibility phenotype in its native host, Laodelphax striatellus. In the Aedes albopictus C/wStr1 mosquito cell line, wStr maintains a robust, persistent infection. MS/MS analyses of gel bands revealed a protein ‘footprint’ dominated by Wolbachia‐encoded chaperones, stress response and cell membrane proteins, including the surface antigen WspA, a peptidoglycan‐associated lipoprotein and a 73 kDa outer membrane protein. Functional classifications and estimated abundance levels of 790 identified proteins suggested that expression, stabilization and secretion of proteins predominate over bacterial genome replication and cell division. High relative abundances of cysteine desulphurase, serine/glycine hydroxymethyl transferase, and components of the α‐ketoglutarate dehydrogenase complex in conjunction with above average abundances of glutamate dehydrogenase and proline utilization protein A support Wolbachia genome‐based predictions for amino acid metabolism as a primary energy source. wStr expresses 15 Vir proteins of a Type IV secretion system and its transcriptional regulator. Proteomic characterization of a robust insect‐associated Wolbachia strain provides baseline information that will inform further development of in vitro protocols for Wolbachia manipulation.

A null mutation in SERPINE1 protects against biological aging in humans

Humans with a rare gene mutation in SERPINE1 live longer and show evidence of protection from aging-related morbidity. Plasminogen activator inhibitor–1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However, the role of PAI-1 in human longevity remains unclear. We hypothesized that a rare loss-of-function mutation in SERPINE1 (c.699_700dupTA), which encodes PAI-1, could play a role in longevity and metabolism in humans. We studied 177 members of the Berne Amish community, which included 43 carriers of the null SERPINE1 mutation. Heterozygosity was associated with significantly longer leukocyte telomere length, lower fasting insulin levels, and lower prevalence of diabetes mellitus. In the extended Amish kindred, carriers of the null SERPINE1 allele had a longer life span. Our study indicates a causal effect of PAI-1 on human longevity, which may be mediated by alterations in metabolism. Our findings demonstrate the utility of studying loss-of-function mutations in populations with geographic and genetic isolation and shed light on a novel therapeutic target for aging.

Factors Associated With Long-Term Weight Loss Following Bariatric Surgery Using 2 Methods for Repeated Measures Analysis

We used electronic health record data from 162 patients enrolled in the NUgene Project (2002-2013) to determine demographic factors associated with long-term (from 1 to up to 9.5 (mean = 5.6) years) weight loss following Roux-en-Y gastric bypass surgery. Ninety-nine (61.1%) patients self-reported white, and 63 (38.9%) self-reported black, mixed, or missing race. The average percent weight loss was -33.4% (standard deviation, 9.3) at 1 year after surgery and -30.7% (standard deviation, 12.5) at the last follow-up point. We used linear mixed and semiparametric trajectory models to test the association of surgical and demographic factors (height, surgery age, surgery weight, surgery body mass index, marital status, sex, educational level, site, International Classification of Diseases code, Current Procedural Terminology code, Hispanic ethnicity, and self-reported race) with long-term percent weight loss and pattern of weight loss. We found that black, mixed, and missing races (combined) in comparison with white race were associated with a decreased percent weight loss of -4.31% (95% confidence interval: -7.30, -1.32) and were less likely to have higher and sustained percent weight loss (P = 0.04). We also found that less obese patients were less likely to have higher and sustained percent weight loss (P = 0.01). These findings may be helpful to patients in setting expectations after weight loss surgery.

Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial.

Importance Wide heterogeneity exists in acute myocardial infarction treatment and outcomes in India. Objective To evaluate the effect of a locally adapted quality improvement tool kit on clinical outcomes and process measures in Kerala, a southern Indian state. Design, Setting, and Participants Cluster randomized, stepped-wedge clinical trial conducted between November 10, 2014, and November 9, 2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December 31, 2016. During 5 predefined steps over the study period, hospitals were randomly selected to move in a 1-way crossover from the control group to the intervention group. Consecutively presenting patients with acute myocardial infarction were offered participation. Interventions Hospitals provided either usual care (control group; n = 10 066 participants [step 0: n = 2915; step 1: n = 2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or care using a quality improvement tool kit (intervention group; n = 11 308 participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432; step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback, checklists, patient education materials, and linkage to emergency cardiovascular care and quality improvement training. Main Outcomes and Measures The primary outcome was the composite of all-cause death, reinfarction, stroke, or major bleeding using standardized definitions at 30 days. Secondary outcomes included the primary outcome’s individual components, 30-day cardiovascular death, medication use, and tobacco cessation counseling. Mixed-effects logistic regression models were used to account for clustering and temporal trends. Results Among 21 374 eligible randomized participants (mean age, 60.6 [SD, 12.0] years; n = 16 183 men [76%] ; n = 13 689 [64%] with ST-segment elevation myocardial infarction), 21 079 (99%) completed the trial. The primary composite outcome was observed in 5.3% of the intervention participants and 6.4% of the control participants. The observed difference in 30-day major adverse cardiovascular event rates between the groups was not statistically significant after adjustment (adjusted risk difference, −0.09% [95% CI, −1.32% to 1.14%]; adjusted odds ratio, 0.98 [95% CI, 0.80-1.21]). The intervention group had a higher rate of medication use including reperfusion but no effect on tobacco cessation counseling. There were no unexpected adverse events reported. Conclusions and Relevance Among patients with acute myocardial infarction in Kerala, India, use of a quality improvement intervention compared with usual care did not decrease a composite of 30-day major adverse cardiovascular events. Further research is needed to understand the lack of efficacy. Trial Registration clinicaltrials.gov Identifier: NCT02256657

Cardiovascular Research Publications from Latin America between 1999 and 2008. A Bibliometric Study

Background Cardiovascular research publications seem to be increasing in Latin America overall. Objective To analyze trends in cardiovascular publications and their citations from countries in Latin America between 1999 and 2008, and to compare them with those from the rest of the countries. Methods We retrieved references of cardiovascular publications between 1999 and 2008 and their five-year post-publication citations from the Web of Knowledge database. For countries in Latin America, we calculated the total number of publications and their citation indices (total citations divided by number of publications) by year. We analyzed trends on publications and citation indices over time using Poisson regression models. The analysis was repeated for Latin America as a region, and compared with that for the rest of the countries grouped according to economic development. Results Brazil (n = 6,132) had the highest number of publications in1999-2008, followed by Argentina (n = 1,686), Mexico (n = 1,368) and Chile (n = 874). Most countries showed an increase in publications over time, leaded by Guatemala (36.5% annually [95%CI: 16.7%-59.7%]), Colombia (22.1% [16.3%-28.2%]), Costa Rica (18.1% [8.1%-28.9%]) and Brazil (17.9% [16.9%-19.1%]). However, trends on citation indices varied widely (from -33.8% to 28.4%). From 1999 to 2008, cardiovascular publications of Latin America increased by 12.9% (12.1%-13.5%) annually. However, the citation indices of Latin America increased 1.5% (1.3%-1.7%) annually, a lower increase than those of all other country groups analyzed. Conclusions Although the number of cardiovascular publications of Latin America increased from 1999 to 2008, trends on citation indices suggest they may have had a relatively low impact on the research field, stressing the importance of considering quality and dissemination on local research policies.

Acute coronary syndrome quality improvement in Kerala (ACS QUIK): Rationale and design for a cluster-randomized stepped-wedge trial

&NA; Ischemic heart disease is the leading cause of death in India, and there are likely more myocardial infarctions in India than in any other country in the world. We have previously reported heterogeneous care for patients with myocardial infarction in Kerala, a state in southern India, including both gaps in optimal care and inappropriate care. Based on that prior work, limitations from previous nonrandomized quality improvement studies and promising gains in process of care measures demonstrated from previous randomized trials, we and the Cardiological Society of India—Kerala chapter sought to develop, implement, and evaluate a quality improvement intervention to improve process of care measures and clinical outcomes for these patients. In this article, we report the rationale and study design for the ACS QUIK cluster‐randomized stepped‐wedge clinical trial (NCT02256657) in which we aim to enroll 15,750 participants with acute coronary syndromes across 63 hospitals. To date, most participants are men (76%) and have ST‐segment elevation myocardial infarction (63%). The primary outcome is 30‐day major adverse cardiovascular events defined as death, recurrent infarction, stroke, or major bleeding. Our secondary outcomes include health‐related quality of life and individual‐ and household‐level costs. We also describe the principal features and limitations of the stepped‐wedge study design, which may be important for other investigators or sponsors considering cluster‐randomized stepped‐wedge trials.

Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies

BACKGROUND Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. METHODS AND RESULTS We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50±5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 × 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. CONCLUSION A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

Sex Differences in the Presentation, Diagnosis, and Management of Acute Coronary Syndromes: Findings From the Kerala-India ACS Registry

BACKGROUND Previous literature from high-income countries has repeatedly shown sex differences in the presentation, diagnosis, and management of acute coronary syndromes (ACS), with women having atypical presentations and undergoing less aggressive diagnostic and therapeutic measures. However, much less data exist evaluating sex differences in ACS in India. OBJECTIVES This study sought to evaluate sex differences in the diagnosis, management, and treatment of patients with ACS in Kerala, India. METHODS The Kerala ACS Registry collected data from 25,748 consecutive ACS admissions (19,923 men and 5,825 women) from 125 hospitals in the Indian state of Kerala from 2007 to 2009. This study evaluated the association between sex differences in presentation, in-hospital management, and discharge care with in-hospital mortality and in-hospital major adverse cardiovascular events (defined as death, reinfarction, stroke, heart failure, or cardiogenic shock). RESULTS Women with ACS were older than men with ACS (64 vs. 59, p < 0.001) and were more likely to have a history of previous myocardial infarction (16% vs. 14%, p < 0.001). Inpatient diagnostics and management and discharge care were similar between sexes. No significant differences between men and women in the outcome of death (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.80 to 1.38) or in the composite outcome of death, reinfarction, stroke, heart failure, or cardiogenic shock (OR: 0.99, 95% CI: 0.79 to 1.25) were seen after adjustment for possible confounding factors. CONCLUSIONS In Kerala, even though women with ACS were older and more likely to have previous myocardial infarction, there were no significant differences in in-hospital and discharge management, in-hospital mortality, or major adverse cardiovascular events between sexes. Whether these results apply to other parts of India or acute presentations of other chronic diseases in low- and middle-income countries warrants further study.