03073nas a2200397 4500008004100000022001400041245013400055210006900189260001300258490000600271520187500277100002002152700002202172700002302194700002002217700002002237700002002257700002002277700003402297700002002331700001902351700001502370700002202385700002102407700001502428700001902443700001902462700002302481700002702504700002202531700001702553700002402570700002302594700002202617856003602639 2016 eng d a1941-329700aPredicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes.0 aPredicting Heart Failure With Preserved and Reduced Ejection Fra c2016 Jun0 v93 a

BACKGROUND: Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF).

METHODS AND RESULTS: Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78-0.82) and validation samples (internal: 0.79; 95% CI, 0.77-0.82 and external: 0.76; 95% CI: 0.71-0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80-0.84) and validation samples (internal: 0.80; 95% CI, 0.78-0.83 and external: 0.76; 95% CI, 0.71-0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison ≤0.02).

CONCLUSIONS: We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.

1 aHo, Jennifer, E1 aEnserro, Danielle1 aBrouwers, Frank, P1 aKizer, Jorge, R1 aShah, Sanjiv, J1 aPsaty, Bruce, M1 aBartz, Traci, M1 aSanthanakrishnan, Rajalakshmi1 aLee, Douglas, S1 aChan, Cheeling1 aLiu, Kiang1 aBlaha, Michael, J1 aHillege, Hans, L1 aHarst, Pim1 aGilst, Wiek, H1 aKop, Willem, J1 aGansevoort, Ron, T1 aVasan, Ramachandran, S1 aGardin, Julius, M1 aLevy, Daniel1 aGottdiener, John, S1 ade Boer, Rudolf, A1 aLarson, Martin, G uhttps://chs-nhlbi.org/node/714003411nas a2200541 4500008004100000022001400041245007900055210006900134260001600203520185300219100002202072700002002094700002102114700001502135700002102150700001902171700003102190700002202221700002202243700001802265700002002283700002302303700002102326700002102347700001902368700001502387700002702402700002002429700002002449700002302469700002102492700002002513700002402533700001902557700002102576700002202597700002202619700001702641700002502658700001902683700002202702700002202724700002302746700002402769700002002793700002002813856003602833 2017 eng d a1879-084400aPredictors and outcomes of heart failure with mid-range ejection fraction.0 aPredictors and outcomes of heart failure with midrange ejection  c2017 Dec 113 a

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.

1 aBhambhani, Vijeta1 aKizer, Jorge, R1 aLima, João, A C1 aHarst, Pim1 aBahrami, Hossein1 aNayor, Matthew1 ade Filippi, Christopher, R1 aEnserro, Danielle1 aBlaha, Michael, J1 aCushman, Mary1 aWang, Thomas, J1 aGansevoort, Ron, T1 aFox, Caroline, S1 aGaggin, Hanna, K1 aKop, Willem, J1 aLiu, Kiang1 aVasan, Ramachandran, S1 aPsaty, Bruce, M1 aLee, Douglas, S1 aBrouwers, Frank, P1 aHillege, Hans, L1 aBartz, Traci, M1 aBenjamin, Emelia, J1 aChan, Cheeling1 aAllison, Matthew1 aGardin, Julius, M1 aJanuzzi, James, L1 aLevy, Daniel1 aHerrington, David, M1 aGilst, Wiek, H1 aBertoni, Alain, G1 aLarson, Martin, G1 ade Boer, Rudolf, A1 aGottdiener, John, S1 aShah, Sanjiv, J1 aHo, Jennifer, E uhttps://chs-nhlbi.org/node/754904686nas a2200541 4500008004100000022001400041245011900055210006900174260001600243520308900259100002303348700001903371700003003390700002203420700002203442700002003464700002203484700002303506700001803529700002103547700002103568700001503589700002003604700002303624700002103647700002103668700001903689700001503708700002703723700002003750700002003770700002103790700002003811700002403831700001903855700002103874700002203895700002203917700002003939700001703959700002503976700002204001700001904023700002404042700002204066700002004088856003604108 2018 eng d a2380-659100aAssociation of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction.0 aAssociation of Cardiovascular Biomarkers With Incident Heart Fai c2018 Jan 103 a

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.

1 ade Boer, Rudolf, A1 aNayor, Matthew1 adeFilippi, Christopher, R1 aEnserro, Danielle1 aBhambhani, Vijeta1 aKizer, Jorge, R1 aBlaha, Michael, J1 aBrouwers, Frank, P1 aCushman, Mary1 aLima, João, A C1 aBahrami, Hossein1 aHarst, Pim1 aWang, Thomas, J1 aGansevoort, Ron, T1 aFox, Caroline, S1 aGaggin, Hanna, K1 aKop, Willem, J1 aLiu, Kiang1 aVasan, Ramachandran, S1 aPsaty, Bruce, M1 aLee, Douglas, S1 aHillege, Hans, L1 aBartz, Traci, M1 aBenjamin, Emelia, J1 aChan, Cheeling1 aAllison, Matthew1 aGardin, Julius, M1 aJanuzzi, James, L1 aShah, Sanjiv, J1 aLevy, Daniel1 aHerrington, David, M1 aLarson, Martin, G1 aGilst, Wiek, H1 aGottdiener, John, S1 aBertoni, Alain, G1 aHo, Jennifer, E uhttps://chs-nhlbi.org/node/760302743nas a2200241 4500008004100000022001400041245013300055210006900188260001300257300001200270490000600282520198600288100002002274700001602294700002202310700002202332700002002354700002002374700002402394700002002418700002702438856003602465 2018 eng d a2213-178700aTemporal Trends in the Incidence of and Mortality Associated With Heart Failure With Preserved and Reduced Ejection Fraction.0 aTemporal Trends in the Incidence of and Mortality Associated Wit c2018 Aug a678-6850 v63 a

OBJECTIVES: This study aimed to determine temporal trends in the incidence of and mortality associated with heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart rate with preserved ejection fraction [HFpEF]) in the community.

BACKGROUND: Major shifts in cardiovascular disease risk factor prevalence and advances in therapies may have influenced HF incidence and mortality.

METHODS: In the FHS (Framingham Heart Study) and CHS (Cardiovascular Health Study), for participants who were ≥60 years of age and free of HF (n = 15,217; 60% women; 2,524 incident HF cases; 115,703 person-years of follow-up), we estimated adjusted incidence rate ratios of HF, HFrEF, and HFpEF from 1990 to 1999 and 2000 to 2009. We compared the cumulative incidence of and mortality associated with HFrEF versus HFpEF within and between decades.

RESULTS: Across the 2 decades, HF incidence rate ratio was similar (p = 0.13). The incidence rate ratio of HFrEF declined (p = 0.0029), whereas HFpEF increased (p < 0.001). Although HFrEF incidence declined more in men than in women, men had a higher incidence of HFrEF than women in each decade (p < 0.001). The incidence of HFpEF significantly increased over time in both men and women (p < 0.001 and p = 0.02, respectively). During follow-up after HF, 1,701 individuals died (67.4%; HFrEF, n = 557 [33%]; HFpEF, n = 474 [29%]). There were no significant differences in mortality rates (overall, cardiovascular disease, and noncardiovascular disease) across decades within HF subtypes or between HFrEF and HFpEF within decade.

CONCLUSIONS: In several U.S. community-based samples from 1990 to 2009, we observed divergent trends of decreasing HFrEF and increasing HFpEF incidence, with stable overall HF incidence and high risk for mortality. Our findings highlight the need to elucidate factors contributing to these observations.

1 aTsao, Connie, W1 aLyass, Asya1 aEnserro, Danielle1 aLarson, Martin, G1 aHo, Jennifer, E1 aKizer, Jorge, R1 aGottdiener, John, S1 aPsaty, Bruce, M1 aVasan, Ramachandran, S uhttps://chs-nhlbi.org/node/7814