Associations Between Sleep Disorders and Hypertensive Disorders of Pregnancy and Materno-fetal Consequences.

PURPOSE OF THE REVIEW: To review the data supporting the associations between sleep disorders and hypertensive disorders of pregnancy, their diagnosis, consequences, treatment, and potential mechanisms. RECENT FINDINGS: The prevalence of sleep-disordered breathing, insomnia, and restless legs syndrome increases as pregnancy progresses secondary to physiologic changes associated with pregnancy. Sleep-disordered breathing is strongly associated with the development of gestational hypertension and preeclampsia, both of which are associated with increased risk of perinatal complications. Diagnosing sleep disorders in pregnant presents added challenges, but polysomnography remains the gold standard for diagnosing sleep-disordered breathing in this group. Sleep disorders, and especially sleep-disordered breathing, are highly prevalent among pregnant women and associated with hypertensive disorders of pregnancy. Clinicians should be mindful of this association and endeavor to identify at-risk women for further evaluation.

Smaller Left Ventricle Size at Noncontrast CT Is Associated with Lower Mortality in COPDGene Participants.

Background Smokers with chronic obstructive pulmonary disease (COPD) have smaller left ventricles (LVs) due to reduced preload. Skeletal muscle wasting is also common in COPD, but less is known about its contribution to LV size. Purpose To explore the relationships between CT metrics of emphysema, venous vascular volume, and sarcopenia with the LV epicardial volume (LVEV) (myocardium and chamber) estimated from chest CT images in participants with COPD and then to determine the clinical relevance of the LVEV in multivariable models, including sex and anthropomorphic metrics. Materials and Methods The COPDGene study (ClinicalTrials.gov identifier: NCT00608764) is an ongoing prospective longitudinal observational investigation that began in 2006. LVEV, distal pulmonary venous blood volume for vessels smaller than 5 mm2 in cross section (BV5), CT emphysema, and pectoralis muscle area were retrospectively extracted from 3318 nongated, unenhanced COPDGene CT scans. Multivariable linear and Cox regression models were used to explore the association between emphysema, venous BV5, pectoralis muscle area, and LVEV as well as the association of LVEV with health status using the St George's Respiratory Questionnaire, 6-minute walk distance, and all-cause mortality. Results The median age of the cohort was 64 years (interquartile range, 57-70 years). Of the 2423 participants, 1806 were men and 617 were African American. The median LVEV between Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and GOLD 4 COPD was reduced by 13.9% in women and 17.7% in men (P < .001 for both). In fully adjusted models, higher emphysema percentage (ß = -4.2; 95% confidence interval [CI]: -5.0, -3.4; P < .001), venous BV5 (ß = 7.0; 95% CI: 5.7, 8.2; P < .001), and pectoralis muscle area (ß = 2.7; 95% CI: 1.2, 4.1; P < .001) were independently associated with reduced LVEV. Reductions in LVEV were associated with improved health status (ß = 0.3; 95% CI: 0.1, 0.4) and 6-minute walk distance (ß = -12.2; 95% CI: -15.2, -9.3). These effects were greater in women than in men. The effect of reduced LVEV on mortality (hazard ratio: 1.07; 95% CI: 1.05, 1.09) did not vary by sex. Conclusion In women more than men with chronic obstructive pulmonary disease, a reduction in the estimated left ventricle epicardial volume correlated with a loss of pulmonary venous vasculature, greater pectoralis muscle sarcopenia, and lower all-cause mortality. © RSNA, 2020 Online supplemental material is available for this article.

Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study.

Rationale: Cor pulmonale (right ventricular [RV] dilation) and cor pulmonale parvus (RV shrinkage) are both described in chronic obstructive pulmonary disease (COPD). The identification of emphysema as a shared risk factor suggests that additional disease characterization is needed to understand these widely divergent cardiac processes.Objectives: To explore the relationship between computed tomography measures of emphysema and distal pulmonary arterial morphology with RV volume, and their association with exercise capacity and mortality in ever-smokers with COPD enrolled in the COPDGene Study.Methods: Epicardial (myocardium and chamber) RV volume (RVEV), distal pulmonary arterial blood vessel volume (arterial BV5: vessels <5 mm2 in cross-section), and objective measures of emphysema were extracted from 3,506 COPDGene computed tomography scans. Multivariable linear and Cox regression models and the log-rank test were used to explore the association between emphysema, arterial BV5, and RVEV with exercise capacity (6-min-walk distance) and all-cause mortality.Measurements and Main Results: The RVEV was approximately 10% smaller in Global Initiative for Chronic Obstructive Lung Disease stage 4 versus stage 1 COPD (P < 0.0001). In multivariable modeling, a 10-ml decrease in arterial BV5 (pruning) was associated with a 1-ml increase in RVEV. For a given amount of emphysema, relative preservation of the arterial BV5 was associated with a smaller RVEV. An increased RVEV was associated with reduced 6-minute-walk distance and in those with arterial pruning an increased mortality.Conclusions: Pulmonary arterial pruning is associated with clinically significant increases in RV volume in smokers with COPD and is related to exercise capacity and mortality in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Declining Lung Function and Cardiovascular Risk: The ARIC Study.

BACKGROUND: Pulmonary dysfunction predicts incident cardiovascular disease (CVD). OBJECTIVES: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. METHODS: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. RESULTS: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). CONCLUSIONS: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Right Ventricular Function, Right Ventricular-Pulmonary Artery Coupling, and Heart Failure Risk in 4 US Communities: The Atherosclerosis Risk in Communities (ARIC) Study.

Importance: Limited data exist on the prevalence and prognostic importance of right ventricular (RV) dysfunction for heart failure (HF) in the general population. Objective: To assess the prevalence of RV dysfunction and its association with HF and mortality in a community-based elderly cohort. Design, Setting, and Participants: Cross-sectional and time-to-event analysis of participants in the Atherosclerosis Risks in the Community (ARIC), a multicenter, population-based cohort study at the fifth study visit from 2011 to 2013, with a median follow-up of 4.1 years. This study included 1004 elderly participants in the ARIC study attending the fifth study visit who underwent both 3-dimensional and 2-dimensional RV echocardiography. Three-dimensional echocardiography data were analyzed between September 15, 2015, and July 24, 2016. Exposures: Right ventricular ejection fraction (RVEF), RV-pulmonary artery (PA) coupling defined by the RVEF/PA systolic pressure (PASP) ratio, and RV longitudinal strain by 3-dimensional echocardiography. Main Outcomes and Measures: For cross-sectional analysis, the prevalence of RV dysfunction across ACCF/AHA HF stages (0; A, at elevated risk for HF but without structural heart disease or clinical HF; B, structural heart disease but without clinical HF; and C, prevalent HF). For time-to-event analysis, a composite of incident HF hospitalization or all-cause death among participants free of HF at visit 5. Results: Of the 1004 participants, mean (SD) age was 76 (5) years, 385 were men (38%), and 121 were black (12%). Mean (SD) RVEF was 53% (8%). Right ventricular EF, RVEF/PASP, and RV longitudinal strain were each progressively lower across advancing HF stages. Using reference limits from stage 0 participants, RVEF was abnormal in 103 asymptomatic persons with stage A HF (15%) and 27 with stage B HF (24%). Among participants free of HF at baseline, lower RVEF and worse RV-PA coupling (ie, lower RVEF/PASP ratio) both were associated with incident HF or death independent of LVEF and N-terminal pro b-type natriuretic peptide (hazard ratio, 1.20; 95% CI, 1.02-1.42 per 5% decrease in RVEF; P = .03; hazard ratio, 1.65, 95% CI, 1.15-2.37 per 0.5 unit decrease in RVEF/PASP ratio; P = .007). Conclusions and Relevance: Right ventricular function and RV-PA coupling declined progressively across American College of Cardiology Foundation/American Heart Association HF stages. Among persons free of HF, lower RVEF was associated with incident HF or death independent of LVEF or N-terminal pro b-type natriuretic peptide.

Left ventricular ejection time is an independent predictor of incident heart failure in a community-based cohort.

AIMS: Systolic time intervals change in the progress of cardiac dysfunction. The usefulness of left ventricular ejection time (LVET) to predict cardiovascular morbidity, however, is unknown. METHODS AND RESULTS: We studied middle-aged African-Americans from one of four cohorts of the Atherosclerosis Risk in Communities study (Jackson cohort, n=1980) who underwent echocardiography between 1993 and 1995. Left ventricular ejection time was measured by pulsed-wave Doppler of the left ventricular outflow tract and related to outcomes. A shorter LVET was associated with younger age, male sex, higher diastolic blood pressure, higher proportion of diabetes, higher heart rate, higher blood glucose levels and worse fractional shortening. During a median follow-up of 17.6 years, 384 (19%) had incident heart failure (HF), 158 (8%) had a myocardial infarction, and 587 (30%) died. In univariable analysis, a lower LVET was significantly associated with increased risk of all events (P<0.05 for all). However, after multivariable adjustment for age, sex, hypertension, diabetes, body mass index, heart rate, systolic and diastolic blood pressure, fractional shortening and left atrial diameter, LVET remained an independent predictor only of incident HF [hazard ratio 1.07 (1.02-1.14), P=0.010 per 10 ms decrease]. In addition, LVET provided incremental prognostic information to the known risk factors included in the Framingham risk score, in regard to predicting all outcomes except for myocardial infarction. CONCLUSION: Left ventricular ejection time is an independent predictor of incident HF in a community-based cohort and provides incremental prognostic information on the risk of future HF and death when added to known risk prediction models.

Smoking and Cardiac Structure and Function in the Elderly: The ARIC Study (Atherosclerosis Risk in Communities).

BACKGROUND: Cigarette smoking has been associated with higher risk of incident heart failure independent of coronary artery disease, but the impact of tobacco use on cardiac structure and function in the general population is uncertain. This study evaluated the relationship between smoking and echocardiographic measures in a large elderly cohort. METHODS AND RESULTS: We studied 4580 participants free of overt coronary artery disease, heart failure, and significant valvular disease from the fifth visit of the ARIC study (Atherosclerosis Risk in Communities) who underwent transthoracic echocardiography. Participants were classified into 3 categories based on self-reported smoking habits: never (43.2%), former (50.5%), and current smokers (6.3%). Pack-years and years of smoking were also estimated. Compared with never smokers, current smokers had greater left ventricular (LV) mass index (80.4±1.1 versus 76.7±0.4 g/m(2); P<0.001), LV mass/volume ratio (1.93±0.03 versus 1.83±0.03 g/mL; P<0.001), higher prevalence of LV hypertrophy (15% versus 9%; P=0.008), and worse diastolic function, as reflected by higher E/E' ratio (11.7±0.2 versus 10.9±0.1; P<0.001), after adjusting for potential confounding factors. In contrast, former smokers showed similar echocardiographic features when compared with never smokers. Furthermore, estimated pack-years and years of smoking, measures of cumulative cigarette exposure, were associated with greater LV mass index, LV mass/volume ratio, and worse diastolic function (higher E/E' ratio) in current smokers after multivariable analysis (all P<0.01). CONCLUSIONS: Active smoking and cumulative cigarette exposure were associated with subtle alterations in LV structure and function in an elderly, community-based population free of overt coronary artery disease and heart failure.

Influence of cigarette smoking on cardiac biomarkers: the Atherosclerosis Risk in Communities (ARIC) Study.

AIMS: Cigarette smoking has been associated with incident heart failure independent of coronary artery disease (CAD), but the mechanisms linking smoking to cardiac damage are not well understood. This study sought to evaluate the relationship between smoking and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively, biomarkers of myocardial wall stress and injury, in a large community-based cohort. METHODS AND RESULTS: We examined the association between smoking history and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4 (1996-1998), as well as the association with change in these biomarkers from Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher cumulative cigarette exposure, assessed by total pack-years, was associated with elevated levels of NT-proBNP (P < 0.001) and hs-TnT (P = 0.01) among ever smokers in multivariable analyses adjusted for potential confounders. After 15 years of follow-up, participants who were active smokers at Visit 4 had greater incidence of elevated NT-proBNP {adjusted proportion = 48% [95% confidence interval (CI) 41, 54] vs. 35 (95% CI 32, 39); P = 0.006} and hs-TnT [adjusted proportion = 32% (95% CI 26, 38) vs. 23 (95% CI 20, 26); P = 0.021] compared with never smokers, adjusting for baseline and follow-up covariates. CONCLUSIONS: In a large community-based cohort free of overt CAD and heart failure, cigarette smoking was associated with biomarkers of myocardial wall stress and injury at baseline as well as with a continued measurable increase in these biomarkers after 15 years of follow-up.

Right Atrial Function in Pulmonary Arterial Hypertension.

BACKGROUND: Elevated right atrial (RA) pressure is an established prognostic measure in pulmonary arterial hypertension (PAH). However, little is known about perturbations in RA function in PAH. METHODS AND RESULTS: Reservoir (RA longitudinal strain [RA LS]), conduit (RA early LS rate), and active (RA late LS rate) phases were assessed by 2D speckle tracking in 65 patients with PAH, 6-minute walk distance ≤450 m, and a pulmonary vascular resistance >800 dynes·s/cm(5), despite therapy with at least 2 PAH-specific medications enrolled in the Imatinib in Pulmonary Arterial Hypertension, a Randomized Efficacy Study (IMPRES) trial and were compared with 30 healthy controls of similar age and sex. We studied the association of RA functional measures with invasive pulmonary hemodynamics, cardiac structure and function, and N-terminal pro brain natriuretic peptide. RA LS and early LS rate were reduced in PAH patients compared with controls (27.1±11.6 versus 56.9±12.7, adjusted P<0.001 and -0.6±0.5 versus -1.5±0.5, adjusted P<0.001, respectively) even after adjusting for RA area and invasive RA pressure, whereas RA late LS rate was similar between groups (-1.4±0.7 versus -1.5±0.4, P=0.42). Among PAH patients, worse RA LS correlated with greater RA size (r=-0.50, P<0.0001) and pressure (r=-0.37, P=0.002), but not pulmonary artery pressure (r=-0.07, P=0.58). Worse RA LS was also associated with right ventricular enlargement and dysfunction and higher N-terminal pro brain natriuretic peptide independent of RA size and pressure. CONCLUSIONS: RA reservoir and passive conduit functions are impaired in PAH, independent of RA size and pressure, and likely reflect right ventricular failure and overload. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00902174.

Sleep Disordered Breathing: Hypertension and Cardiac Structure and Function.

Obstructive sleep apnea (OSA) is a common form of sleep disordered breathing and has a relatively high prevalence in the general population. The frequency and severity of OSA is associated with age, male sex, and obesity, and OSA has been linked to cardiovascular complications and death. Importantly, OSA has a strong association with both prevalent and incidental hypertension and has a particularly high prevalence in patients with resistant hypertension. In these patients, CPAP and other OSA-directed treatments have been proposed as therapy to help control blood pressure (BP), especially in patients who have not attained optimal BP control despite maximum pharmacological therapy. OSA has also been associated with alterations in cardiac structure and function, although most studies are small and highly limited in study design. Existing data suggest an association between OSA greater left ventricle (LV) mass and hypertrophy that appears independent of confounders including hypertension and obesity. Although less clear and more controversial, OSA severity has been linked to LV systolic and diastolic function, pulmonary hypertension, and right ventricular hypertrophy. Further studies are needed to confirm the potential causal role of OSA in these observed associations with cardiac abnormalities.

Impact of lowering pulmonary vascular resistance on right and left ventricular deformation in pulmonary arterial hypertension.

AIMS: As pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality, particularly among patients with right ventricular (RV) dysfunction, we aimed to determine the impact of therapy to reduce pulmonary vascular resistance (PVR) on RV and LV deformation in PAH. METHODS AND RESULTS: Right ventricular free wall longitudinal strain (FWLS) and LV global circumferential strain (CS) were measured at baseline, 12 weeks, and 24 weeks in 68 patients with advanced PAH randomized to imatinib or placebo in the Imatinib in Pulmonary arterial hypertension, a Randomized Efficacy Study (IMPRES) trial, and compared with 30 healthy controls. Compared with controls, PAH was associated with impaired RV FWLS (-15.9 ± 5.4 vs. -30.8 ± 4.3, respectively; P < 0.0001) and LV septal CS (-24.2 ± 8.2 vs. -31.4 ± 5.3, respectively, P < 0.0001), but not LV global CS. Improvement in PVR and mean pulmonary artery pressure (MPAP) over a 24-week period was significantly associated with improvement in RV FWLS (r = 0.39, P = 0.02; 0.33, P = 0.04 respectively), LV global CS (r = 0.61, P = 0.0001; r = 0.60, P = 0.0001, respectively), and LV septal CS (r = 0.50, P = 0.005; r = 0.56, P = 0.002, respectively). These associations were most robust with LV global and septal CS. Imatinib therapy was associated with improvement in RV FWLS compared with placebo. CONCLUSIONS: PAH is associated with impaired biventricular deformation. Reduction in PVR is associated with improvements in both RV and LV deformation, coupled to improvements in MPAP and stroke volume index, with LV global and septal CS the strongest correlates of these changes. RV FWLS is sensitive to treatment effect, demonstrating greater improvement with imatinib compared with placebo. TRIAL REGISTRATION: NCT00902174.

Sleep apnea is associated with subclinical myocardial injury in the community. The ARIC-SHHS study.

RATIONALE: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, although the underlying mechanisms are not well understood. OBJECTIVES: We aimed to determine whether more severe OSA, measured by the Respiratory Disturbance Index (RDI), is associated with subclinical myocardial injury and increased myocardial wall stress. METHODS: A total of 1,645 participants (62.5 ± 5.5 yr and 54% women) free of coronary heart disease and heart failure and participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies underwent overnight polysomnography and measurement of high-sensitivity troponin T (hs-TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP). MEASUREMENTS AND MAIN RESULTS: OSA severity was defined using conventional clinical categories: none (RDI ≤ 5), mild (RDI 5-15), moderate (RDI 15-30), and severe (RDI > 30). Hs-TnT, but not NT-proBNP, was associated with OSA after adjusting for 17 potential confounders (P = 0.02). Over a median of 12.4 (interquartile range, 11.6-13.1) years follow-up, hs-TnT was related to risk of death or incident heart failure in all OSA categories (P ≤ 0.05 in each category). CONCLUSIONS: In middle-aged to older individuals, OSA severity is independently associated with higher levels of hs-TnT, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure. OSA was not associated with NT-proBNP levels after adjusting for multiple possible confounders.