Association of Pulmonary Function With Late-Life Cardiac Function and Heart Failure Risk: The ARIC Study.

Background Pulmonary and cardiac functions decline with age, but the associations of pulmonary dysfunction with cardiac function and heart failure (HF) risk in late life is not known. We aimed to determine the associations of percent predicted forced vital capacity (ppFVC) and the ratio of forced expired volume in 1 second (FEV1) to forced vital capacity (FVC; FEV1/FVC) with cardiac function and incident HF with preserved or reduced ejection fraction in late life. Methods and Results Among 3854 HF-free participants in the ARIC (Atherosclerosis Risk in Communities) cohort study who underwent echocardiography and spirometry at the fifth study visit (2011-2013), associations of FEV1/FVC and ppFVC with echocardiographic measures, cardiac biomarkers, and risk of HF, HF with preserved ejection fraction, and HF with reduced ejection fraction were assessed. Multivariable linear and Cox regression models adjusted for demographics, body mass index, coronary disease, atrial fibrillation, hypertension, and diabetes. Mean age was 75±5 years, 40% were men, 19% were Black, and 61% were ever smokers. Mean FEV1/FVC was 72±8%, and ppFVC was 98±17%. In adjusted analyses, lower FEV1/FVC and ppFVC were associated with higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; both P<0.001) and pulmonary artery pressure (P<0.004). Lower ppFVC was also associated with higher left ventricular mass, left ventricular filling pressure, and high-sensitivity C-reactive protein (all P<0.01). Lower FEV1/FVC was associated with a trend toward higher risk of incident HF with preserved ejection fraction (hazard ratio [HR] per 10-point decrease, 1.31; 95% CI, 0.98-1.74; P=0.07) and HF with reduced ejection fraction (HR per 10-point decrease, 1.24; 95% CI, 0.91-1.70; P=0.18), but these associations did not reach statistical significance. Lower ppFVC was associated with incident HF with preserved ejection fraction (HR per 10-unit decrease, 1.21; 95% CI, 1.04-1.41; P=0.013) but not with HF with reduced ejection fraction (HR per 10-unit decrease, 0.90; 95% CI, 0.76-1.07; P=0.24). Conclusions Subclinical reductions in FEV1/FVC and ppFVC differentially associate with cardiac function and HF risk in late life.

Lung function and cardiovascular disease: A link.

The relationship between lung and heart diseases has long been recognized, with necropsy studies demonstrating silent myocardial infarctions or coronary artery calcification in patients with advanced emphysema as the death cause. Improvements in non-invasive techniques and epidemiologic approaches established that lung and cardiovascular diseases frequently coexist in mid and late life. Even among those without diagnosed lung disease, lower than expected forced vital capacity, forced expiratory volume in 1 s, and their ratio each portend greater risk of developing cardiovascular risk factors including hypertension, obesity, and metabolic syndrome, and for incident cardiovascular diseases including left heart failure, atrial fibrillation and stroke. Greater longitudinal declines in these spirometric measures are further associated with cardiovascular morbidity and mortality. While obstructive ventilatory patterns are more common, restrictive ventilatory patterns seem to demonstrate an independent and more robust association with cardiovascular diseases such as heart failure. These subclinical alterations in pulmonary function also relate to subclinical abnormalities of cardiac structure and function. Although the biologic pathways linking pulmonary and cardiovascular dysfunction are not clear, chronic systemic inflammation appears to be one important underlying pathophysiologic link. Despite the growing evidence of lung dysfunction as a cardiovascular risk factor, spirometric evaluation is still underutilized in clinical practice, particularly among cardiac patients, and optimal therapeutic and preventive strategies are still unclear. In this review, we address the current knowledge and controversies regarding the links between lung function and cardiovascular disease.

Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis.

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p=0.001), used oral bisphosphonates less frequently (34% × 50%; p=0.005), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p=0.03) and ΔCTX (-69 [-76; -50] × -54 [-72; -23]; p=0.002) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41-0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

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

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.

Unanswered Questions Regarding Blood Pressure Management for HF Prevention.

PURPOSE OF REVIEW: Evaluate the relevant new findings regarding hypertension treatment and heart failure prevention published in the past 3 years. RECENT FINDINGS: In a recent secondary analysis of Systolic Blood Pressure Intervention Trial (SPRINT), randomization of more than 9000 patients > 50 years old with high cardiovascular risk but without diabetes to intensive treatment targeting blood pressure < 120/80 mmHg compared to standard treatment targeting < 140/90 mmHg significantly reduced incident heart failure. While such benefits outweighed potential harm, adverse events including renal dysfunction, hypotension, and syncope occurred more frequently with intensive treatment. Following SPRINT, existing guidelines differ in their recommendations and controversies still exist. Key persistent questions include the role of intensive treatment in younger adults and those at lower cardiovascular risk and optimal approaches to translate clinical trial findings into clinical practice in a sustainable fashion. Aggressively treating hypertension to targets below 120/80 mmHg prevents heart failure in high-risk patients. However, evidence is lacking to younger patients and those at lower cardiovascular risk.