@article {7549, title = {Predictors and outcomes of heart failure with mid-range ejection fraction.}, journal = {Eur J Heart Fail}, year = {2017}, month = {2017 Dec 11}, abstract = {

AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.

METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49\%], HFpEF (EF >=50\%), and HFrEF (EF <=40\%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P~<= 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P~<= 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95\% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95\% CI 1.20-1.90, P~= 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95\% CI 1.41-1.73, P~= 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P~= 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P~= 0.78).

CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.

}, issn = {1879-0844}, doi = {10.1002/ejhf.1091}, author = {Bhambhani, Vijeta and Kizer, Jorge R and Lima, Jo{\~a}o A C and van der Harst, Pim and Bahrami, Hossein and Nayor, Matthew and de Filippi, Christopher R and Enserro, Danielle and Blaha, Michael J and Cushman, Mary and Wang, Thomas J and Gansevoort, Ron T and Fox, Caroline S and Gaggin, Hanna K and Kop, Willem J and Liu, Kiang and Vasan, Ramachandran S and Psaty, Bruce M and Lee, Douglas S and Brouwers, Frank P and Hillege, Hans L and Bartz, Traci M and Benjamin, Emelia J and Chan, Cheeling and Allison, Matthew and Gardin, Julius M and Januzzi, James L and Levy, Daniel and Herrington, David M and van Gilst, Wiek H and Bertoni, Alain G and Larson, Martin G and de Boer, Rudolf A and Gottdiener, John S and Shah, Sanjiv J and Ho, Jennifer E} } @article {7603, title = {Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction.}, journal = {JAMA Cardiol}, year = {2018}, month = {2018 Jan 10}, abstract = {

Importance: Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood.

Objective: To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population.

Design, Setting, and Participants: This study included 4 longitudinal community-based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017.

Exposures: The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6.

Main Outcomes and Measures: Development of incident HFpEF and incident HFrEF.

Results: Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95\% CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95\% CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95\% CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95\% CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95\% CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95\% CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95\% CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95\% CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95\% CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95\% CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95\% CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF.

Conclusions and Relevance: Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

}, issn = {2380-6591}, doi = {10.1001/jamacardio.2017.4987}, author = {de Boer, Rudolf A and Nayor, Matthew and deFilippi, Christopher R and Enserro, Danielle and Bhambhani, Vijeta and Kizer, Jorge R and Blaha, Michael J and Brouwers, Frank P and Cushman, Mary and Lima, Jo{\~a}o A C and Bahrami, Hossein and van der Harst, Pim and Wang, Thomas J and Gansevoort, Ron T and Fox, Caroline S and Gaggin, Hanna K and Kop, Willem J and Liu, Kiang and Vasan, Ramachandran S and Psaty, Bruce M and Lee, Douglas S and Hillege, Hans L and Bartz, Traci M and Benjamin, Emelia J and Chan, Cheeling and Allison, Matthew and Gardin, Julius M and Januzzi, James L and Shah, Sanjiv J and Levy, Daniel and Herrington, David M and Larson, Martin G and van Gilst, Wiek H and Gottdiener, John S and Bertoni, Alain G and Ho, Jennifer E} } @article {7812, title = {The Association of Obesity and Cardiometabolic Traits With Incident~HFpEF and HFrEF.}, journal = {JACC Heart Fail}, volume = {6}, year = {2018}, month = {2018 Aug}, pages = {701-709}, abstract = {

OBJECTIVES: This study evaluated the associations of obesity and cardiometabolic traits with incident heart failure with preserved versus reduced ejection fraction (HFpEF vs. HFrEF). Given known sex differences in HF subtype, we examined men and women separately.

BACKGROUND: Recent studies suggest that obesity confers greater risk of HFpEF versus HFrEF. Contributions of associated metabolic traits to HFpEF are less clear.

METHODS: We studied 22,681 participants from 4 community-based cohorts followed for incident HFpEF versus HFrEF (ejection fraction >=50\% vs.~<50\%). We evaluated the association of body mass index (BMI) and cardiometabolic traits with incident HF subtype using Cox models.

RESULTS: The mean age was 60 {\textpm} 13 years, and 53\% were women. Over a median follow-up of 12 years, 628 developed incident HFpEF and 835 HFrEF. Greater BMI portended higher risk of HFpEF compared with HFrEF (hazard ratio [HR]: 1.34 per 1-SD increase in BMI; 95\% confidence interval [CI]: 1.24 to 1.45 vs. HR: 1.18; 95\% CI: 1.10 to 1.27). Similarly, insulin resistance (homeostatic model assessment of insulin resistance) was associated with HFpEF (HR: 1.20 per 1-SD; 95\% CI: 1.05 to 1.37), but not HFrEF (HR: 0.99; 95\% CI: 0.88 to 1.11; p~< 0.05 for difference HFpEF vs. HFrEF). We found that the differential association of BMI with HFpEF versus HFrEF was more pronounced among women (p for difference HFpEF vs. HFrEF~= 0.01) when compared with men (p~= 0.34).

CONCLUSIONS: Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among~women and may underlie sex differences in HF subtypes.

}, issn = {2213-1787}, doi = {10.1016/j.jchf.2018.05.018}, author = {Savji, Nazir and Meijers, Wouter C and Bartz, Traci M and Bhambhani, Vijeta and Cushman, Mary and Nayor, Matthew and Kizer, Jorge R and Sarma, Amy and Blaha, Michael J and Gansevoort, Ron T and Gardin, Julius M and Hillege, Hans L and Ji, Fei and Kop, Willem J and Lau, Emily S and Lee, Douglas S and Sadreyev, Ruslan and van Gilst, Wiek H and Wang, Thomas J and Zanni, Markella V and Vasan, Ramachandran S and Allen, Norrina B and Psaty, Bruce M and van der Harst, Pim and Levy, Daniel and Larson, Martin and Shah, Sanjiv J and de Boer, Rudolf A and Gottdiener, John S and Ho, Jennifer E} }