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Multicenter Study
. 2019 Jun 5;2(6):e195321.
doi: 10.1001/jamanetworkopen.2019.5321.

Association of Undifferentiated Dyspnea in Late Life With Cardiovascular and Noncardiovascular Dysfunction: A Cross-sectional Analysis From the ARIC Study

Sergio H R Ramalho  1   2 , Mario Santos  3 , Brian Claggett  2 , Kunihiro Matsushita  4 , Dalane W Kitzman  5 , Laura Loehr  6 , Scott D Solomon  2 , Hicham Skali  2 , Amil M Shah  2
Affiliations
Multicenter Study

Association of Undifferentiated Dyspnea in Late Life With Cardiovascular and Noncardiovascular Dysfunction: A Cross-sectional Analysis From the ARIC Study

Sergio H R Ramalho et al. JAMA Netw Open. .

Abstract

Importance: Undifferentiated dyspnea is common in late life, but the relative contribution of subclinical cardiac dysfunction is unknown. Impairments in cardiac structure and function may be characteristics of undifferentiated dyspnea in elderly people, providing potential insights into occult heart failure (HF).

Objective: To quantify the association of undifferentiated dyspnea with cardiac dysfunction after accounting for other potential contributors.

Design, setting, and participants: This cross-sectional study used data from Atherosclerosis Risk in Communities study participants 65 years and older who attended the fifth study visit (from 2011 to 2013) and had not been diagnosed with HF, chronic obstructive pulmonary disease, morbid obesity, or severe kidney disease. Analyses were conducted from October 2017 to June 2018.

Exposures: Dyspnea measured using the modified Medical Research Council scale, with a score less than 2 classified as none to mild and a score of 2 or more classified as moderate to severe.

Main outcomes and measures: Using multivariable logistic regression, the association of undifferentiated dyspnea was defined using cardiac structure, systolic and diastolic function, pulmonary pressure (echocardiography), pulmonary function (spirometry), glomerular filtration rate, hemoglobin, body mass index, depression, and physical performance. The population-attributable risk was calculated for each dysfunction metric.

Results: Among 4342 participants (mean [SD] age, 75.9 [5.0] years; 2533 [58.3%] women), 1173 (27.0%) had undifferentiated dyspnea. Moderate to severe dyspnea was present in 574 participants (13.2%) and was associated with left ventricular (LV) hypertrophy (odds ratio [OR], 1.53; 95% CI, 1.25-1.87; P < .001) and LV diastolic (OR, 1.46; 95% CI, 1.20-1.78; P < .001) and systolic (OR, 1.28; 95% CI, 1.05-1.56; P = .02) dysfunction. Moderate to severe dyspnea was also associated with obstructive (OR, 1.59; 95% CI, 1.28-1.99; P < .001) and restrictive (OR, 2.56; 95% CI, 1.99-3.27; P < .001) findings on spirometry, renal impairment (OR, 1.32; 95% CI, 1.08-1.61; P = .01), anemia (OR, 1.72; 95% CI, 1.39-2.12; P < .001), lower (OR, 2.77; 95% CI, 2.18-3.51; P < .001) and upper (OR, 1.82; 95% CI, 1.49-2.23; P < .001) extremity weakness, depression (OR, 3.01; 95% CI, 2.24-4.25; P < .001), and obesity (OR, 2.35; 95% CI, 1.95-2.83; P < .001). After accounting for these, moderate to severe dyspnea was associated with LV hypertrophy (OR, 1.30; 95% CI, 1.01-1.67; P = .04) and was not associated with systolic or diastolic function. In contrast, in the fully adjusted model, other organ system measures were associated with dyspnea, except for glomerular filtration rate and grip strength. The population-attributable risk of dyspnea associated with obesity alone was 22.6% compared with 5.8% for LV hypertrophy.

Conclusions and relevance: Undifferentiated dyspnea is multifactorial in older adults, and this study showed an association with obesity. When accounting for other relevant organ systems, cardiovascular function poorly discriminated those with vs those without dyspnea. Therefore, dyspnea should not be assumed to represent occult HF in this population.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Matsushita reported grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Kitzman reported grants from AstraZeneca, Bayer, Novartis, and NIH; personal fees from Corvia Medical, AbbVie, Akros, Bayer, Boehringer Ingelheim, CinRx Pharma, Duke Clinical Research Institute, Merck and Co, Novartis, Relypsa, St. Luke’s Hospital (Kansas City, Missouri); and stock ownership from Gilead Sciences. Dr Loehr reported grants from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study. Dr Solomon reported grants from Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bellerophon Therapeutics, Bayer, Bristol-Myers Squib, Celladon, Cytokinetics, Eidos Therapeutics, Gilead Sciences, GlaxoSmithKline, Ionis Pharmaceuticals, LoneStar Heart, Mesoblast, MyoKardia, NIH, NHLBI, Novartis, Sanofi Pasteur, and Theracos and personal fees from Akros, Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia Medical, Cytokinetics, Gilead Sciences, GlaxoSmithKline, Ironwood, Merck and Co, Myokardia, Novartis, Roche, Takeda Pharmaceutical, Theracos, Quantum Genetics, Cardurion Pharmaceuticals, AOBiome, Janssen Pharmaceuticals, Cardiac Dimensions, and Tenaya Therapeutics outside the submitted work. Dr Shah reported grants from NIH and NHLBI during the conduct of this study and reported personal fees from Bellerophon Therapeutics and Philips Ultrasound and research support from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Number of Abnormal Metrics of Cardiac and Noncardiac Organ Function Among Participants With Moderate to Severe vs No or Mild Dyspnea
After adjusting for age, sex, and race/ethnicity, participants with moderate to severe dyspnea had significantly more simultaneous dysfunctions (median [interquartile range], 3 [2-4]) than those with no or mild dyspnea (median [interquartile range], 2 [1-3]) (P < .001).
Figure 2.
Figure 2.. Adjusted Associations of Cardiovascular and Noncardiovascular Organ Dysfunction With Undifferentiated Dyspnea in the Elderly Population
The fully adjusted model was adjusted for age, sex, race/ethnicity, and all listed metrics of organ dysfunction. LV indicates left ventricle; NA, not applicable; OR, odds ratio; RR, relative risk. aP = .05.
See this image and copyright information in PMC

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