Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure (HF) or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants between 2000–2002 with follow-up for incident heart failure and cardiovascular death (“death”) until January 2008. RV volumes and mass were available for 4204 participants. The study sample (N = 4,144) was 61.4 ± 10.1 years old and 47.6 % male. The presence of RV hypertrophy (increased RV mass) was associated with a more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (HR = 2.52, 95%CI 1.55–4.10, p < 0.001) and a doubling of risk (or more) with left ventricular mass at the mean value or lower (p for interaction = 0.05).
RV hypertrophy was associated with the risk of heart failure or death in a multi-ethnic population free of clinical cardiovascular disease at baseline.
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension; survival
Cor pulmonale has long been described in very severe chronic obstructive pulmonary disease (COPD) and emphysema. Cross-sectional results from population-based studies show that left ventricular filling and a variety of vascular measures in the systemic circulation are abnormal in preclinical COPD and emphysema and that a predominant vascular change in COPD and emphysema is endothelial and microvascular dysfunction. These findings suggest that pulmonary vascular changes may occur early in COPD and emphysema and might contribute to pathogenesis. However, longitudinal epidemiologic studies with direct measures of the pulmonary vasculature are lacking; therefore, inferences are limited at present. New imaging-based approaches to the assessment of the pulmonary vasculature are applicable to epidemiologic studies and may help in defining the relationship of pulmonary vascular damage to progression of COPD and emphysema. These measures may also provide imaging-based surrogate markers, and novel therapeutics targeted to the pulmonary vasculature might reduce symptoms and improve function in these common diseases.
chronic obstructive pulmonary disease; pulmonary emphysema; pulmonary hypertension; vascular disease; pulmonary vasculature
epidemiology; survey; urban health
Current guidelines recommend separate spirometry reference equations for whites, African Americans, and Mexican Americans, but the justification for this recommendation is controversial. The authors examined the statistical justification for race/ethnic-specific reference equations in adults in the Third National Health and Nutrition Examination Survey (1988–1994) and the Multi-Ethnic Study of Atherosclerosis Lung Study (2000–2006). Spirometry was measured following American Thoracic Society guidelines. “Statistical justification” was defined as the presence of effect modification by race/ethnicity among never-smoking participants without respiratory disease or symptoms and was tested with interaction terms for race/ethnicity (× age and height) in regression models. There was no evidence of effect modification by race/ethnicity for forced expiratory volume in 1 second, forced vital capacity, or the forced expiratory volume in 1 second/forced vital capacity ratio among white, African-American, and Mexican-American men or women on an additive scale or a log scale. Interaction terms for race/ethnicity explained less than 1% of variability in lung function. The mean lung function for a given age, gender, and height was the same for whites and Mexican Americans but was lower for African Americans. Findings were similar in the Multi-Ethnic Study of Atherosclerosis Lung Study. The associations of age and height with lung function are similar across the 3 major US race/ethnic groups. Multiethnic rather than race/ethnic-specific spirometry reference equations are applicable for the US population.
African Americans; age groups; body height; European continental ancestry group; Hispanic Americans; respiratory function tests; spirometry
Forced expiratory volume in one second strongly predicts mortality from cardiovascular disease. FEV1 has been associated with aortic stiffness a strong independent predictor of cardiovascular mortality. However, the anatomical site and possible mechanisms linking aortic stiffness and lung function are unknown. We therefore examined if FEV1 and CT percent emphysema were associated with calcification of the abdominal aorta or reduced distensibility of the proximal thoracic aorta.
The Multi-Ethnic Study of Atherosclerosis (MESA) measured aortic calcification on cardiac and abdominal CT scans and proximal aortic distensibility using magnetic resonance among participants aged 45–84 years without clinical cardiovascular disease. Spirometry was measured following ATS/ERS guidelines and percent emphysema was measured in the lung fields of cardiac CT scans. Multivariate analyses adjusted for age, sex, race/ethnicity and cardiovascular risk factors.
Of 1,917 participants with aortic distensibility measures, 13% were current and 38% were former smokers. Eighteen percent had airflow limitation without asthma. FEV1 was associated with the extent of distal aortic calcification (0.76; 95%CI 0.60–0.97, p=0.02) but not proximal aortic calcification or proximal aortic distensibility (−0.04 mmHg−1; 95%CI −0.16–0.09 mmHg−1, p=0.60). Percent emphysema was associated with neither measure.
FEV1 was associated with severity of distal aortic calcification where it was present independently of smoking and other cardiovascular risk factors but not with distensibility or calcification of the proximal aorta.
forced expiratory volume; pulmonary emphysema; aorta; calcification; compliance
Maximal inspiratory pressure (MIP) is an important and non-invasive index of diaphragm strength and an independent predictor of all-cause mortality. The ability of adults over a wide age range and multiple ethnicities to perform MIP tests has previously not been evaluated.
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited white, African-American, Hispanic and Chinese-American participants ages 45–84 years and free of clinical cardiovascular disease in six US cities. MIP was measured using standard techniques among 3849 MESA participants. The MIP quality goal was 5 maneuvers, with the two largest values matching within 10 cmH2O. Correlates of MIP quality and values were assessed in logistic and linear regression models.
The 3849 MESA-Lung participants with MIP measures were 51% female, 35% white, 26% African-American, 23% Hispanic, and 16% Chinese-American. Mean MIP±SD was 73±26 cmH2O for women and 97±29 cmH2O for men. The quality goal was achieved by 83% of the cohort and was associated with female gender, older age, race/ethnicity, study site, low FEV1/FVC ratio, and wheeze with dyspnea. The multivariate correlates of MIP were male gender, younger age, higher BMI, shorter height, higher FVC, higher systolic blood pressure (in women) and health status (in men). There were no clinically important race/ethnic differences in MIP values.
Race-specific reference equations for MIP are unnecessary in the United States. More than 80% of adults can be successfully coached for 5 maneuvers with repeatability within 10 cmH2O.
diaphragm strength; respiratory muscle strength; maximal inspiratory pressure; quality control; pulmonary function testing
Dairy products contain vitamin D and other nutrients that may be beneficial for lung function, but are also high in fats that may have mixed effects on lung function. However, the overall associations of dairy intake with lung density and lung function have not been studied.
We examined the cross-sectional relations between dairy intake and CT lung density and lung function in the Multi-Ethnic Study of Atherosclerosis (MESA). Total, low-fat and high-fat dairy intakes were quantified from food frequency questionnaire responses of men and women, aged 45–84 years, free of clinical cardiovascular disease. The MESA-Lung Study assessed CT lung density from cardiac CT imaging and prebronchodilator spirometry among 3,965 MESA participants.
Total dairy intake was inversely associated with apical-basilar difference in percent emphysema and positively associated with FVC (the multivariate-adjusted mean difference between the highest and the lowest quintile of total dairy intake was −0.92 (p for trend=0.04) for apical-basilar difference in percent emphysema and 72.0 mL (p=0.01) for FVC). Greater low-fat dairy intake was associated with higher alpha (higher alpha values indicate less emphysema) and lower apical-basilar difference in percent emphysema (corresponding differences in alpha and apical-basilar difference in percent emphysema were 0.04 (p=0.02) and −0.98 (p=0.01) for low-fat dairy intake, respectively). High-fat dairy intake was not associated with lung density measures. Greater low- or high-fat dairy intake was not associated with higher FEV1, FVC and FEV1/FVC.
Higher low-fat dairy intake but not high-fat dairy intake was associated with moderately improved CT lung density.
dairy intake; lung density; emphysema; lung function; chronic obstructive pulmonary disease
Airflow obstruction is independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined if an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations.
The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Spirometry, carotid intima-media thickness, ankle-brachial index and coronary artery calcium were measured using standard protocols. Percent of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors including C-reactive protein.
Decrements in the FEV1 and FEV1/FVC were associated with greater internal carotid intima-media thickness among smokers (P=0.03 and P<0.001, respectively) whereas percent emphysema was associated with reduced ankle-brachial index regardless of smoking history (P=0.004). Coronary artery calcium was associated with neither lung function (prevalence ratio for severe airflow obstruction: 0.99; 95% CI, 0.91 to 1.07) nor percent emphysema.
An obstructive pattern of spirometry and emphysema are associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to coronary artery calcium.
We examined the relationship between forced expiratory volume in 1 s (FEV1), airflow obstruction, and incident heart failure (HF) in black and white, middle-aged men and women in four US communities.
Methods and results
Lung volumes by standardized spirometry and information on covariates were collected on 15 792 Atherosclerosis Risk in Communities (ARIC) cohort participants in 1987–89. Incident HF was ascertained from hospital records and death certificates up to 2005 in 13 660 eligible participants. Over an average follow-up of 14.9 years, 1369 (10%) participants developed new-onset HF. The age- and height-adjusted hazard ratios (HRs) for HF increased monotonically over descending quartiles of FEV1 for both genders, race groups, and smoking status. After multivariable adjustment for traditional cardiovascular risk factors and height, the HRs [95% confidence intervals (CIs)] of HF comparing the lowest with the highest quartile of FEV1 were 3.91 (2.40–6.35) for white women, 3.03 (2.12–4.33) for white men, 2.11 (1.33–3.34) for black women, and 2.23 (1.37–3.59) for black men. The association weakened but remained statistically significant after additional adjustment for systemic markers of inflammation. The multivariable adjusted incidence of HF was higher in those with FEV1/forced vital capacity <70% vs. ≥70%: HR 1.44 (95% CI 1.20–1.74) among men and 1.40 (1.13–1.72) among women. A consistent and positive association with HF was seen for self-reported diagnosis of emphysema and chronic obstructive pulmonary disease, but not for asthma.
In this large population-based cohort with long-term follow-up, low FEV1 and an obstructive respiratory disease were strongly and independently associated with the risk of incident HF.
Lung function; COPD; Heart failure; Risk factors; Cohort study
Handheld spirometers have several advantages over desktop spirometers but worries persist regarding their reproducibility and validity. We undertook an independent examination of an ultrasonic flow-sensing handheld spirometer.
Laboratory methods included reproducibility and validity testing using a waveform generator with standard American Thoracic Society (ATS) waveforms, in-line testing, calibration adaptor testing, and compression of the mouthpiece. Clinical testing involved repeated testing of 24 spirometry-naive volunteers and comparison to a volume-sensing dry rolling seal spirometer.
The EasyOne Diagnostic spirometer exceeded standard thresholds of acceptability for ATS waveforms. In-line testing yielded valid results with relative differences (mean ± SD) between the EasyOne and the reference spirometer for the forced vital capacity (FVC) of 0.03±0.23 L and the forced expiratory volume in one second (FEV1) of −0.06±0.09 L. The calibration adaptor showed no appreciable problems, but extreme compression of the mouthpiece reduced measures. In clinical testing, coefficients of variation and limits of agreement were, respectively: 3.3% and 0.24 L for the FVC; 2.6% and 0.18 L for the FEV1; and 1.9% and 0.05 for the FEV1/FVC ratio. The EasyOne yielded lower values than the reference spirometry (FVC: −0.12 L; FEV1: −0.17 L; FEV1/FVC ratio: −0.02). Limits of agreement were within criteria for FVC but not for the FEV1, possibly due to a training effect.
The EasyOne spirometer yielded generally reproducible results that were generally valid compared to laboratory-based spirometry. The use of this handheld spirometer in clinical, occupational and research settings seems justified.
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
RESEARCH DESIGN AND METHODS
We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH.
Methods and Results
We performed a randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at four centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was six-minute walk distance (6MWD) at six months. Sixty-five subjects were randomized when the trial was terminated by the DSMB after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6MWD, there was no significant difference in the 6MWD at six months between aspirin (n = 32) and placebo (n = 33) [placebo-corrected difference = −0.5 m (95%CI, −28.4 – 27.4 m), p = 0.97] or between simvastatin (n = 32) and placebo (n = 33) [placebo-corrected difference = −27.6 m (95%CI, −59.6 – 4.3 m), p = 0.09]. There tended to be more major bleeding episodes with aspirin compared to placebo (4 events vs. 1 event, respectively, p = 0.17).
Neither aspirin nor simvastatin had a significant effect on the 6MWD, although patients randomized to simvastatin tended to have a lower 6MWD at six months. These results do not support the routine treatment of patients with PAH with these medications.
pulmonary hypertension; clinical trial; anti-platelet agents; endothelial dysfunction
To determine whether the self-reported diagnosis of adults who present to the emergency department (ED) with an acute exacerbation of either asthma or chronic obstructive pulmonary disease (COPD) is validated by medical record review.
This is cross-sectional study of 78 consecutive adults, 55 years and older, presenting to 3 EDs with symptoms suggestive of an exacerbation of asthma or COPD. We used current spirometric guidelines for a “spirometrically validated” diagnosis of COPD (eg, postbronchodilator forced expiratory volume in 1 second/forced ventilatory capacity b70%). Patients without office spirometry result were classified with COPD using clinical validation based on at least one of the following: primary care physician diagnosis of COPD, chronic bronchitis, or emphysema in the medical record or chest radiography, chest computed tomography, or arterial blood gas (ABG) diagnostic of COPD.
Among 60 patients who self-reported diagnosis of COPD, 98% (95% confidence interval, 89-100) had clinically validated or spirometrically validated COPD. In addition, 83% (95% confidence interval, 59-96) of patients who reported either asthma only or no respiratory disease had clinically validated or spirometrically validated COPD. In no case was the chest radiograph or the ABG useful as a stand-alone test in establishing the diagnosis of COPD.
Patients 55 years and older presenting to the ED with acute asthma or COPD, even those with clinical symptoms but no diagnosis of COPD, are likely to have COPD. Clinicians should maintain a high index of suspicion for COPD when older asthma patients deny COPD.
The pulmonary vasculature is an important site of renin-angiotensin metabolism. While angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (collectively AIABs) have a role in left ventricular (LV) disease, the impact of AIABs on right ventricular (RV) function is unknown. AIAB use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were obtained via cardiac magnetic resonance imaging. The relationship between AIAB use and RV measures was assessed using multivariable linear regression, stratified by race/ethnicity, and adjusted for multiple covariates. AIAB use was associated with lower RV mass (-0.7 g, 95% confidence interval [CI] -1.3 to -0.1, P=0.03) in African Americans (N=1012) after adjustment for multiple covariates including LV mass. Among Caucasians (N=1591), AIAB use was associated with larger RV end-diastolic volume (3.7 mL, 95% CI 0.7-6.8, P=0.02) after adjustment for LV volume. No significant associations were seen between AIAB use and other RV measures or in Hispanic or Chinese American participants. AIAB use was associated with RV morphology in a race-specific and LV-independent manner, suggesting the renin-angiotensin system may play a unique role in RV structure and function. The use of AIABs in those with RV dysfunction warrants further study.
angiotensin-converting enzyme inhibitor; angiotensin II receptor blockers; right ventricle; epidemiology; renin-angiotensin system
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
Increased left ventricular (LV) mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000–2002 in the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, population-based, US study. Over a median follow-up of 4.8 years, 745 (29%) participants developed hypertension. In a fully adjusted model including baseline blood pressure, the relative risks of incident hypertension from the lowest to highest LV mass quartile were 1.00 (referent), 1.13 (95% confidence interval (CI): 0.89, 1.43), 1.28 (95% CI: 1.00, 1.63), and 1.78 (95% CI: 1.38, 2.30) (P < 0.001 for linear trend). Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model (P = 0.044 for linear trend). In a final model containing both quartiles of LV mass and LV mass/volume along with all covariates including baseline blood pressure, higher LV mass quartiles were associated with incident hypertension (P < 0.001 for linear trend), whereas higher LV mass/volume quartiles were not (P = 0.643 for linear trend). In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.
hypertension; hypertrophy, left ventricular; magnetic resonance imaging; risk factors
Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH.
ASA-STAT is a Phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in six minutes at six months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups.
Screening and Enrollment
We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin.
This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed.
Pulmonary hypertension; Endothelial dysfunction; platelets; Clinical trial
Coronary artery calcification (CAC) and thoracic aortic calcificatio (TAC) are frequently detected on ungated multi-detector computed tomography (MDCT) performed for lung evaluations. We sought to evaluate concordance of CAC and TAC scores on ungated (thoracic) and ECG-gated (cardiac) MDCT scans.
Fifty patients, enrolled in the Genetic Epidemiology of COPD study (COPDGene), were recruited to undergo gated CAC scans using 64-detector row CT, in addition to the ungated thoracic studies already being obtained as part of their study evaluation. Coronary and thoracic calcium was measured similarly (Agatston score, requiring 3 contiguous voxels of >130 Hounsfield units) using low-dose ungated studies and ECG-gated MDCT performed at the same scanning session. Intertechnique scoring variability and concordance were calculated.
Correlations between gated and ungated CAC and TAC were excellent (r = 0.96). The relative differences (median variability) measured by ECG-gated vs. ungated MDCT were relatively high for CAC (44%) but not for TAC (8%). Prevalence of depicted CAC (n=33, 66%) and TAC (n=21, 42%) were coincident between ECG-gated and ungated MDCT, respectively (inter-technique concordance 100%). Bland-Altman plots for CAC demonstrated mean differences of 354 (CI 169–538) and 16.1(CI −89–121).
Low-dose ungated MDCT is reliable for prediction of the presence of CAC and assessment of Agatston score. Concordance between methods and between TAC and CAC is high. This technique should allow for atherosclerotic disease risk stratification among patients undergoing ungated lung CT evaluation without requiring additional scanning. Measurement of TAC is almost as accurate from gated CT, and CAC scores are highly concordant.
Rationale: Sex hormones have effects on the left ventricle, but hormonal influences on the right ventricle (RV) are unknown.
Objectives: We hypothesized that sex hormones would be associated with RV morphology in a large cohort free of cardiovascular disease.
Methods: Sex hormones were measured by immunoassay and RV ejection fraction (RVEF), stroke volume (RVSV), mass, end-diastolic volume, and end-systolic volume (RVESV) were measured by cardiac magnetic resonance imaging in 1,957 men and 1,738 postmenopausal women. The relationship between each hormone and RV parameter was assessed by multivariate linear regression.
Measurements and Main Results: Higher estradiol levels were associated with higher RVEF (β per 1 ln[nmol/L], 0.88; 95% confidence interval [CI], 0.32 to 1.43; P = 0.002) and lower RVESV (β per 1 ln[nmol/L], −0.87; 95% CI, −1.67 to −0.08; P = 0.03) in women using hormone therapy. In men, higher bioavailable testosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.97; 95% CI, 0.20 to 3.73; P = 0.03) and greater RV mass and volumes (P ≤ 0.01). Higher dehydroepiandrosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.37; 95% CI, 0.15 to 2.59; P = 0.03) and greater RV mass (β per 1 ln[nmol/L], 0.25; 95% CI, 0.00 to 0.49; P = 0.05) and volumes (P ≤ 0.001) in women.
Conclusions: Higher estradiol levels were associated with better RV systolic function in women using hormone therapy. Higher levels of androgens were associated with greater RV mass and volumes in both sexes.
sex; sex hormones; right ventricle
Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114).
SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex.
After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48–5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19–1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02–12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes.
SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study.
Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.
Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.
Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.
Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p = 0.008 and p = 0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p = 0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.
Inflammation; thrombosis; hypertension; pulmonary
The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.
We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.
119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.
Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.
Airway hyperresponsiveness; asthma; Chronic obstructive pulmonary disease; emphysema; Exacerbation; Gas-trapping
The impact of cardiovascular risk factors on the left ventricle is well known but their impact on right ventricle has not been studied using advanced imaging techniques. The purpose of this study was to determine the relation between cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images were analyzed in 4204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression models were used to study the cross sectional association between individual RV parameters and risk factors. All RV parameters except ejection fraction decreased with age (p<0.0001). RV mass was positively associated with systolic blood pressure (+0.4g, p<0.0001) and high density lipoprotein (HDL) cholesterol (+0.2g, p<0.0001); inversely with diastolic blood pressure (−0.3g, p<0.0001) and total cholesterol (−0.2g, p<0.01). RV end diastolic volume was positively associated with systolic blood pressure (+1.6ml, p<0.01) and HDL cholesterol (+1.8ml, p<0.0001); and inversely with diastolic blood pressure (−2.2 ml, p<0.0001), total cholesterol (−1.4ml, p<0.0001), current smoking (−2.7ml, p<0.05) and diabetes mellitus (−3.1ml, p<0.01). RV ejection fraction was positively related with systolic blood pressure (+1.0%, p<0.0001), HDL cholesterol (+0.4%, p<0.0001) and inversely with diastolic blood pressure (−0.7%, p<0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and HDL cholesterol are associated with subclinical changes in RV mass and volumes.