Dataset Information

Proteomics of JHS samples identifies proteins associated with heart failure

ABSTRACT: RELEVANCE: Identifying early plasma protein biomarkers that predict the development of heart failure (HF) following myocardial infarction (MI) will help to stratify at risk subjects and provide insight into more effective therapeutic strategies. OBJECTIVE/HYPOTHESIS: The goal of this study was to determine markers of HF in African Americans, using plasma samples collected before the development of symptoms. We propose that early plasma glycoprotein changes will link to later development of heart failure. ApolipoproteinF will be the strongest indicator. METHODS: Plasma samples from a subset of Jackson Heart Study participants with a history of MI but without prevalent heart failure (HF) at visit 2 (2005-2008) were analyzed by glycoproteomics. Individuals were grouped into those who experienced subsequent HF hospitalization after visit 2 (n=15; 3 men/ 12 women) and those without HF hospitalization through 2012 (n=45; 24 men/ 21 women). N-linked plasma glycopeptides were quantified by solid-phase extraction coupled to mass spectrometry and identified using RefSeq and SwissProt. Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis (IPA) and linked to clinical characteristics.

INSTRUMENT(S): Q Exactive

TISSUE(S): Blood Plasma

SUBMITTER: Elizabeth Flynn

LAB HEAD: Merry L Lindsey, Ph.D.

PROVIDER: PXD009870 | Pride | 2018-08-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	JHS_10_MI_no_HF_Male.pep.xml	Pepxml
	JHS_10_MI_no_HF_Male.prot.xml	Xml
	JHS_10_MI_no_HF_Male.raw	Raw
	JHS_11_MI_no_HF_Male.pep.xml	Pepxml
	JHS_11_MI_no_HF_Male.prot.xml	Xml

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Publications

LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling.

DeLeon-Pennell Kristine Y KY Mouton Alan J AJ Ero Osasere K OK Ma Yonggang Y Padmanabhan Iyer Rugmani R Flynn Elizabeth R ER Espinoza Ingrid I Musani Solomon K SK Vasan Ramachandran S RS Hall Michael E ME Fox Ervin R ER Lindsey Merry L ML

Basic research in cardiology 20180821 5

Sex differences in heart failure development following myocardial infarction (MI) are not fully understood. We hypothesized that differential MI signaling could explain variations in outcomes. Analysis of the mouse heart attack research tool 1.0 (422 mice; young = 5.4 ± 0.1; old = 23.3 ± 0.1 months of age) was used to dissect MI signaling pathways, which was validated in a new cohort of mice (4.8 ± 0.2 months of age); and substantiated in humans. Plasma collected at visit 2 from the MI subset of ...[more]

PMID: 30132266

Publication: 1/2

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Project description:OBJECTIVES:This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND:HFpEF affects women more frequently than men. Sex differences in responses to effects of mineralocorticoid antagonists have not been reported. METHODS:This was an exploratory, post hoc, non-pre-specified analysis of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Subjects with symptomatic HF and a left ventricular ejection fraction ?45% were randomized to spironolactone or placebo therapy. Subjects enrolled from the Americas were analyzed. The primary outcome was a composite of cardiovascular (CV) death, cardiac arrest, or HF hospitalization. Secondary outcomes included all-cause mortality, CV, and non-CV mortality and CV, HF, and non-CV hospitalization. Sex differences in outcomes and treatment effects were determined using time-to-event analysis. RESULTS:In total, 882 of 1,767 subjects (49.9%) were women. Women were older with fewer comorbidities but worse patient-reported outcomes. There were no sex differences in outcomes in the placebo arm or in response to spironolactone for the primary outcome or its components. Spironolactone therapy was associated with reduced all-cause mortality in women (hazard ratio: 0.66; p = 0.01) but not in men (pinteraction = 0.02). CONCLUSIONS:In TOPCAT, women and men presented with different clinical profiles and similar clinical outcomes. The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironolactone therapy in women, with a significant interaction between sex and treatment arm. Prospective evaluation is needed to determine whether spironolactone therapy may be effective for treatment of HFpEF in women. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

Project description:BACKGROUND:National heart failure (HF) hospitalization rates have not been appropriately age standardized by sex or race/ethnicity. Reporting hospital utilization trends by subgroup is important for monitoring population health and developing interventions to eliminate disparities. METHODS AND RESULTS:The National Inpatient Sample (NIS) was used to estimate the crude and age-standardized rates of HF hospitalization between 2002 and 2013 by sex and race/ethnicity. Direct standardization was used to age-standardize rates to the 2000 US standard population. Relative differences between subgroups were reported. The national age-adjusted HF hospitalization rate decreased 30.8% from 526.86 to 364.66 per 100?000 between 2002 and 2013. Although hospitalizations decreased for all subgroups, the ratio of the age-standardized rate for men compared with women increased from 20% greater to 39% (P trend=0.002) between 2002 and 2013. Black men had a rate that was 229% (P trend=0.141) and black women, 240% (P trend=0.725) with reference to whites in 2013 with no significant change between 2002 and 2013. Hispanic men had a rate that was 32% greater in 2002 and the difference narrowed to 4% (P trend=0.047) greater in 2013 relative to whites. For Hispanic women, the rate was 55% greater in 2002 and narrowed to 8% greater (P trend=0.004) in 2013 relative to whites. Asian/Pacific Islander men had a 27% lower rate in 2002 that improved to 43% (P trend=0.040) lower in 2013 relative to whites. For Asian/Pacific Islander women, the hospitalization rate was 24% lower in 2002 and improved to 43% (P trend=0.021) lower in 2013 relative to whites. CONCLUSIONS:National HF hospitalization rates have decreased steadily during the recent decade. Disparities in HF burden and hospital utilization by sex and race/ethnicity persist. Significant population health interventions are needed to reduce the HF hospitalization burden among blacks. An evaluation of factors explaining the improvements in the HF hospitalization rates among Hispanics and Asian/Pacific Islanders is needed.

Project description:Prior studies have documented racial and ethnic disparities in hospitalization among patients with heart failure (HF). However, racial/ethnic differences in trajectories of hospitalization following the diagnosis of HF have not been well characterized. This study examined racial/ethnic differences in individual-level trajectories of hospitalization in older adults with diagnosed HF.Data from a nationally representative prospective cohort of US men and women aged 45 years and older were used to examine the number of hospitalizations reported every 24 months. Participants who were non-Hispanic white, non-Hispanic black, and Hispanic with a reported diagnosis of HF (n=3011) were followed from 1998 to 2014. Results showed a quadratic change in the number of reported hospitalizations following HF diagnosis, with an average of 2.36 (95% confidence interval [CI], 2.19-2.53; P<0.001) hospitalizations within 24 months that decreased by 0.35 (95% CI, -0.45 to -0.25; P<0.001) every 24 months and subsequently increased by 0.03 (95% CI, 0.02-0.05; P<0.001) thereafter. In men, there were no racial/ethnic differences in hospitalizations reported at the time of diagnosis; however, Hispanic men had significant declines in hospitalizations after diagnosis (Hispanic×time=-0.52; 95% CI, -0.99 to -0.05 [P=0.031]) followed by a sizeable increase in hospitalizations at later stages of disease (Hispanic×time2=0.06; 95% CI, 0.00-0.12 [P=0.047]). In women, hospitalizations were consistently high following their diagnosis and black women had significantly more hospitalizations throughout follow-up than white women (black=0.28; 95% CI, 0.00-0.55 [P=0.048]). Racial/ethnic disparities varied by geography and the differences remained significant after adjusting for multiple sociodemographic, psychosocial, behavioral, and physiological factors.There were significant racial/ethnic differences in trajectories of hospitalization following the diagnosis of HF in US men and women. Racial/ethnic disparities varied by place of residence and the differences persisted after adjustment for multiple risk factors. The findings have important implications that may be crucial to planning the immediate and long-term delivery of care in patients with HF to reduce potentially preventable hospitalizations.

Project description:To better guide strategies intended to reduce high rates of 30-day readmission after hospitalization for heart failure (HF), acute myocardial infarction (MI), or pneumonia, further information is needed about readmission diagnoses, readmission timing, and the relationship of both to patient age, sex, and race.To examine readmission diagnoses and timing among Medicare beneficiaries readmitted within 30 days after hospitalization for HF, acute MI, or pneumonia.We analyzed 2007-2009 Medicare fee-for-service claims data to identify patterns of 30-day readmission by patient demographic characteristics and time after hospitalization for HF, acute MI, or pneumonia. Readmission diagnoses were categorized using an aggregated version of the Centers for Medicare & Medicaid Services' Condition Categories. Readmission timing was determined by day after discharge.We examined the percentage of 30-day readmissions occurring on each day (0-30) after discharge; the most common readmission diagnoses occurring during cumulative periods (days 0-3, 0-7, 0-15, and 0-30) and consecutive periods (days 0-3, 4-7, 8-15, and 16-30) after hospitalization; median time to readmission for common readmission diagnoses; and the relationship between patient demographic characteristics and readmission diagnoses and timing.From 2007 through 2009, we identified 329,308 30-day readmissions after 1,330,157 HF hospitalizations (24.8% readmitted), 108,992 30-day readmissions after 548,834 acute MI hospitalizations (19.9% readmitted), and 214,239 30-day readmissions after 1,168,624 pneumonia hospitalizations (18.3% readmitted). The proportion of patients readmitted for the same condition was 35.2% after the index HF hospitalization, 10.0% after the index acute MI hospitalization, and 22.4% after the index pneumonia hospitalization. Of all readmissions within 30 days of hospitalization, the majority occurred within 15 days of hospitalization: 61.0%, HF cohort; 67.6%, acute MI cohort; and 62.6%, pneumonia cohort. The diverse spectrum of readmission diagnoses was largely similar in both cumulative and consecutive periods after discharge. Median time to 30-day readmission was 12 days for patients initially hospitalized for HF, 10 days for patients initially hospitalized for acute MI, and 12 days for patients initially hospitalized for pneumonia and was comparable across common readmission diagnoses. Neither readmission diagnoses nor timing substantively varied by age, sex, or race.Among Medicare fee-for-service beneficiaries hospitalized for HF, acute MI, or pneumonia, 30-day readmissions were frequent throughout the month after hospitalization and resulted from a similar spectrum of readmission diagnoses regardless of age, sex, race, or time after discharge.