Hypertension as a Road to Treatment of Heart Failure with Preserved Ejection Fraction

Hicklin, Harry E; Gilbert, Olivia; Fan, Yu; Brooks, Jeremy; Upadhya, Bharathi

doi:10.1007/s11906-020-01093-7

Cited by 16 publications

(13 citation statements)

References 106 publications

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“…This supports the hypothesis of HFpEF as a comorbidity driven systemic syndrome (89,90). We found that hypertensive heart disease was the most discriminant feature for HFpEF, which has been viewed as a major etiology for diastolic HF involving cardiac hypertrophy and myocardial stiffness (91,92). In contrast, ischemic etiologies including myocardial infarction characterized HFrEF consistent with other studies (93).…”

Section: Discussionsupporting

confidence: 90%

A Network medicine approach to study comorbidities in heart failure with preserved ejection fraction

Lanzer¹,

Valdeolivas²,

Pepin³

et al. 2023

Preprint

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Background Comorbidities are expected to impact pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, comorbidity profiles are usually reduced to a few comorbid disorders. Systems medicine approaches can model multiple comorbidities to help to improve our understanding of HFpEF. Methods We retrospectively explored 569 comorbidities documented in 29,074 HF patients, including 8,062 HFpEF and 6,585 heart failure with reduced ejection fraction (HFrEF) patients from a German university hospital. To analyze comorbidity profiles, first we assessed differences between comorbidity profiles by HF subtype. We fit machine learning classifiers to discriminate between HFpEF and HFrEF patients to interpret important comorbidities. Then we built a network to represent comorbid relationships in HF patients (HFnet) and identified main disease clusters. Lastly, we performed novel gene candidate prediction for HFpEF by linking the HFnet to a multi-layer gene network by integrating multiple databases (HFhetnet). To corroborate HFpEF candidate genes, we collected transcriptomic data in a murine HFpEF model. We compared predicted genes with the murine disease signature as well as with the literature. Results We found that comorbidity profiles vary more in association with HFpEF/HFrEF status than with age or sex. The comorbidities present in HFpEF patients were more diverse than those in HFrEF, and included neoplastic, osteologic and rheumatoid disorders, among others. Disease communities in the HFnet captured important comorbidity concepts of HF patients which could be assigned to HF subtypes, age groups and sex. Within the HFhetnet, we predicted novel gene candidates, including genes involved in fibrosis (COL3A1, MMP1, LOX), oxidative stress (NOS1, GSST1, XDH) and endoplasmic reticulum stress (ATF6). Finally, predicted genes were significantly overrepresented in the murine transcriptomic disease signature. Conclusion We applied systems medicine concepts to analyze comorbidity profiles in a HF patient cohort. We were able to identify disease clusters that helped to characterize HF patients. We derived a distinct comorbidity profile for HFpEF, which was leveraged to suggest novel candidate genes via network propagation. The identification of distinctive comorbidity profiles and candidate genes from routine clinical data will provide insights that may be leveraged to improve diagnosis and treatment for HFpEF patients.

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Section: Discussionsupporting

confidence: 90%

A Network medicine approach to study comorbidities in heart failure with preserved ejection fraction

Lanzer¹,

Valdeolivas²,

Pepin³

et al. 2023

Preprint

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“…In our study, the HF phenotype with the highest BMI was HFpEF. Hypertension is the most important cause of HFpEF [29]. In our study, nearly half of the patients with HFpEF were found to have hypertension.…”

Section: (# ))+#$5+')%%(# )+And#$)*%')and%(# ))%#$And)')!)(# *%)# # J...supporting

confidence: 44%

Baseline characteristics of outpatients with heart failure according to phenotype: preliminary analysis from SMYRNA-HF registry

Şentürk

Çelik

Bekar

et al. 2022

The European Research Journal

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Objectives: SMYRNA-HF study is a prospective multicenter registry study to determine the profiles of patients with heart failure (HF) in Turkey. This study aimed to present the baseline characteristics of preliminary cohort by comparing them according to different HF phenotypes. Methods: The first SMYRNA-HF cohort included outpatients with HF from 9 centers. Patients were classified into three HF phenotypes as HF with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) as recommended by guidelines. Results: Overall, 298 patients were included in this preliminary analysis that 57% of the patients were classified as having HFrEF, 33.3% as having HFpEF, and 9.7% as having HFmrEF. Female gender was more common in HFpEF (p = 0.003). Age, frequency of diabetes mellitus, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker, use of beta-blocker, use of daily loop diuretic, heart rate, blood urea nitrogen levels, lipid profiles, hemoglobin, white blood cell, platelet levels were similar among three HF phenotypes. Body mass index (BMI) (p < 0.001), frequency of hypertension (HT) (p < 0.001), and atrial fibrillation (AF) (p = 0.015) were higher in HFpEF. Ischemic etiology (p < 0.001) was less frequent in HFpEF. Use of mineralocorticoid receptor antagonist was higher in HFrEF (p < 0.001).

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“…Interestingly, the majority of patients with a HFpEF diagnosis are hypertensive (57). As a new animal model of HFpEF, the SS NPPA-/rat presents a unique opportunity to study the complex cardiorenal interaction in hypertension (58). According to a recent metaanalysis that compared sacubitril/valsartan (ARNi) combination with traditional drugs, ARNi significantly improved echocardiography and HF biomarkers, and it reduced the incidence of hyperkalemia and renal dysfunction in patients with chronic HF (59).…”

Section: Discussionmentioning

confidence: 99%

Effects of elevation of ANP and its deficiency on cardiorenal function

Ilatovskaya¹,

Levchenko²,

Winsor³

et al. 2022

JCI Insight

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Hypertension as a Road to Treatment of Heart Failure with Preserved Ejection Fraction

Cited by 16 publications

References 106 publications

A Network medicine approach to study comorbidities in heart failure with preserved ejection fraction

A Network medicine approach to study comorbidities in heart failure with preserved ejection fraction

Baseline characteristics of outpatients with heart failure according to phenotype: preliminary analysis from SMYRNA-HF registry

Effects of elevation of ANP and its deficiency on cardiorenal function

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