Kanako Teramoto, Mário Santos, Brian Claggett, Jenine E. John, Scott D. Solomon, Dalane Kitzman, Aaron R. Folsom, Mary Cushman, Kunihiro Matsushita, Hicham Skali, Amil M. Shah
Abstract
Heart failure (HF) risk is highest in late life, and impaired pulmonary vascular function is a risk factor for HF development. However, data regarding the contributors to and prognostic importance of pulmonary vascular dysfunction among HF-free elders in the community are limited and largely restricted to pulmonary hypertension. Our objective was to define the prevalence and correlates of abnormal pulmonary pressure, resistance, and compliance and their association with incident HF and HF phenotype (left ventricular [LV] ejection fraction [LVEF] ≥ or < 50%) independent of LV structure and function.
Introduction
Pulmonary vascular disease predicts worse outcomes in cardiovascular and pulmonary diseases [1] and is most commonly secondary to left heart, lung, venous thromboembolic, and primary pulmonary vascular diseases [2]. Although most commonly manifest clinically as pulmonary hypertension (PH), the pulmonary circulation can also be characterized in terms of pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC), which are inversely related measures of hydraulic load [3]. In addition to elevated left ventricular (LV) filling pressure, higher pulmonary pressures may result from reciprocal changes in PVR and PAC. Indeed, recent autopsy-based data demonstrate evidence of global pulmonary vascular remodeling in patients with heart failure (HF) and PH [4].
Importantly, these pulmonary hemodynamic measures are not redundant, and pulmonary pressure may remain normal despite impairments in PVR and PAC [5]. Pulmonary pressure and vascular resistance increase with age [6,7], in parallel with age-associated changes in LV compliance and filling pressure, pulmonary function, and vascular function [8,9]. Although prior studies have described the association of PASP with incident HF, few data are available regarding the prevalence, causes, and prognostic implications of PH and vascular dysfunction in the elderly.
Discussion
Pulmonary vascular function is known to change with age, and pulmonary vascular dysfunction is emerging as an important contributor to HF in general and HFpEF in particular. This study defines the prevalence of pulmonary vascular dysfunction—comprehensively characterized based on pressure, resistance, and compliance—in an elderly community-based sample, quantifies its association with cardiac versus pulmonary dysfunction, and establishes its prognostic importance for incident HFpEF and HFrEF. Worse PASP, PVR, and PAC were each associated with higher NT-proBNP and greater risk of incident HF independent of LV measures. Our data therefore build on previous reports showing functional [36] and histological changes of pulmonary vessels in patients with HF [4,37], by extending this concept to the elderly at risk for incident HF, using a comprehensive characterization of pulmonary vascular function.
Citation:Teramoto K, Santos M, Claggett B, John JE, Solomon SD, Kitzman D, et al. (2020) Pulmonary vascular dysfunction among people aged over 65 years in the community in the Atherosclerosis Risk In Communities (ARIC) Study: A cross-sectional analysis. PLoS Med 17(10): e1003361. https://doi.org/10.1371/journal.pmed.1003361
Academic Editor:Kazem Rahimi, University of Oxford, UNITED KINGDOM
Received:December 3, 2019; Accepted: August 31, 2020; Published: October 15, 2020
Copyright:© 2020 Teramoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The ARIC datasets are available through BioLINCC, with appropriate study approvals consistent with NIH policies. Data request forms through BioLINCC can be accessed at https://biolincc.nhlbi.nih.gov/studies/aric/.
Funding:The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268 201100012C). The Longitudinal Investigation of Thromboembolism Etiology study was funded by grant R01HL59367. The work for this manuscript was also supported by NHLBI grants R01HL135008, R01HL143224, R01HL150342, R01HL148218, and K24HL152008 (AMS) and a Watkins Discovery Award from the Brigham and Women’s Heart and Vascular Center (AMS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AMS reports receiving research support from Novartis through the Brigham and Women’s Hospital and consulting fees from Bellerophon and Philips Ultrasound. SDS reports receiving research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, and Theracos and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, and Tremeau. The remaining authors report no competing interests.
Abbreviations: ARIC, Atherosclerosis Risk in Communities; BMI, body mass index; CAD, coronary artery disease; CHD, coronary heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; DPAP, diastolic pulmonary artery pressure; ESC HFA, European Society of Cardiology Heart Failure Association; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HF, heart failure; HFpEF, HF with preserved LVEF; HFrEF, HF with reduced LVEF; IRB, institutional review board; LAVi, left atrial volume index; LV, left ventricular; LVEDD, LV end-diastolic diameter; LVEF, LV ejection fraction; LVMi, LV mass index; MI, myocardial infarction; MPAP, mean pulmonary artery pressure; MWT, mean wall thickness; NT-proBNP, N-terminal prohormone brain natriuretic peptide; PAC, pulmonary arterial compliance; PAD, peripheral artery disease; PAR, population attributable risk; PASP, pulmonary artery systolic pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RC time, resistance-compliance product; RV, right ventricular; RVFAC, RV fractional area change; RWT, relative wall thickness; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology; SV, stroke volume; TA S’, tricuspid annular peak systolic velocity; TR, tricuspid regurgitation; VTE, venous thromboembolism; VTI, time-velocity integral; WU, Wood unit.
