Abstract
OBJECTIVES
The study aimed to examine whether a history of asthma from childhood is associated with adulthood left ventricular (LV) mass.
BACKGROUND
Asthma has been related to various cardiovascular risk factors affecting LV hypertrophy; however, no prospective study has analyzed the relation between a history of asthma from childhood and markers of LV mass among asymptomatic young adults.
METHODS
Prospective analyses were performed among 1118 Bogalusa Heart Study participants (average age at follow-up: 36.7±5.1), with a baseline history of self-reported asthma collected since childhood (average age at baseline: 26.8±10.1). LV mass (g) was assessed using 2-dimensional guided M-mode echocardiography and indexed for body height (m2.7) as LV mass index (LVMI, g/m2.7). A multivariate linear mixed model was fitted for the repeated measures.
RESULTS
After an average 10.4±7.5 years of follow-up, participants with a history of asthma from childhood had a greater LV mass (167.6 vs. 156.9, p=0.01) and LVMI (40.7 vs. 37.7, p<0.01) with adjustment for age, gender, race, smoking status, antihypertensive medicine, heart rate, and systolic blood pressure (SBP). The difference of LVMI between asthma and non-asthma group remained significant after additional adjustment for body mass index (39.0 vs. 37.1, p=0.03) and high sensitive-c reaction protein (38.4 vs. 36.6, p=0.04). In addition, we found significant interactions between SBP and asthma on LV mass and LVMI (p for interaction<0.01, respectively). The associations between asthma and LV measures appeared to be stronger among prehypertensive and hypertensive participants (SBP≥130 mm Hg) compared with those with normal SBP (<130 mm Hg) (regression coefficient: 39.5 vs. 2.3 for LV mass; and 9.0 vs. 0.9 for LVMI).
CONCLUSIONS
Our findings indicate that a history of asthma is associated with higher LVMI, and such association is stronger among participants with prehypertension and hypertension.
Introduction
Left ventricular hypertrophy is recognized as target-organ damage due to a chronic increase in pressure and volume overload, with an estimated prevalence of 14.9% for male and 9.1% for female in the general population, and 36%–41% among hypertensive populations (1,2). LV mass indexed to height2.7 (LVMI) predicts incident events, progression, and severity stages of heart failure (3). Increased LVMI, a cardiac subclinical measure indicating the extent of LV hypertrophy, is an independent risk factor of death and major cardiovascular (CV) outcomes (4,5). Besides traditional CV risk factors, emerging evidence from both experimental and observational studies has linked chronic inflammation to increased LV mass (6,7).
Asthma is a chronic inflammatory disorder in which the airway becomes inflamed, narrow and swell, causing coughing, wheezing, shortness of breath and/or chest tightness. Prevalence of asthma has been growing during the past decade with an estimated current prevalence of 8.6% in children (8) and 7.4% in adults (9). Emerging evidence from epidemiological studies has shown that adulthood asthma is associated with increased risk of premature deaths (10), coronary heart disease (11), and stroke (12). However, there is only one study analyzing the relation between adult asthma and heart failure (13), and one cross-sectional study assessing the association between asthma and LV hypertrophy in the elders (14). No prospective study has assessed the relation between a history of asthma from childhood and LV mass. We hypothesized that having a history of asthma from childhood might be related to increased LV mass in a later life.
In this study, we performed prospective association analyses between a history of asthma from childhood and LV mass in adulthood in the Bogalusa Heart Study, a largest and longest ongoing, community-based, biracial, children’s cohort study of natural history of CV risk factors and its impact on vascular and metabolic changes throughout the lifespan since 1973. In addition, we were particularly interested in testing the interactions between asthma and all other covariates on LV mass, such as demographics and major cardiovascular disease risk factors.
Methods
Study cohort
The Bogalusa Heart Study is a biracial (65% white and 35% black), community-based, long-term investigation of risk factors and natural history of cardiovascular disease (15). Twenty-three repeated cross-sectional surveys were conducted since 1973, resulted in serial observations every 2 to 3 years from childhood through adulthood. Baseline information on asthma was collected among 8289 individuals during 1983–2007. Follow-up outcomes of cardio subclinical markers were measured from 1995 till now. After excluding subjects who only had either baseline (n=6464) or follow-up data (n=161) and whose cardio markers were measured before self-reported asthma (n=20), the rest formed a longitudinal study cohort, with one to four times of follow-ups. In addition, to minimize the potential bias due to abnormal cardiovascular conditions, we excluded 52 participant (139 records of echocardiography) with a self-reported or physician-diagnosed heart disease across all surveys during the follow-up (including heart attack, stroke, angina pectoris, ventricular arrhythmia, mitral valve prolapse, valve replacement, enlarged left ventricle, congestive cardiac failure, blockage in ventricle, tachyarrhythmia, mitral valve stenosis, heart murmur, unspecified mitral disease, congenital heart disease, arteritis, bypass surgery, and angioplasty). All subjects in this study (n=1118) gave informed written consent at each examination, and for those under 18 years of age, the written consent of a parent/guardian was obtained. Study protocols were approved by the biomedical committee of the Tulane University Institutional Review Board.
History of asthma
Information on asthma history was obtained by questionnaire. During 1983 to 1994, asthma prevalence was measured by the child’s parent or guardian responding affirmatively to the question “does your child now have asthma or has your child had asthma in the past?”. For children, the age of asthma diagnosis was approximated as the time the questionnaire was completed. After 1994, young adults aged from 18 to 50 years of old were asked “do you now have asthma or have you had asthma in the past?”, and for those reporting a history of asthma, the age asthma diagnosis was determined by answering the question “when were you firstly diagnosed with asthma?”. If this information was missing, the time that the questionnaire was completed became the proxy time. Among all 8289 individuals (12647 records), 3189 participants provided a self-reported history of asthma (7547 records) in 2 to 6 survey cycles. For whom with multiple times of asthma episodes, the first report of asthma was used as the baseline for asthmatic subjects, and the first report of no asthma for those without asthma in any survey cycle.
Assessment of left ventricular mass
As described elsewhere (16–19), imaging and Doppler echocardiograms were performed by trained sonographers to measure left ventricular (LV) dimensions, using a Toshiba digital ultrasound instrument (Xario SSA-660A). By using 2-dimensional guided M-mode echocardiography with 2.25- and 3.5-MHz transducers, the parasternal long- and short-axis views were obtained for accessing LV end-diastolic and end-systolic measurements in duplicate, and then the mean was calculated. A necropsy-validated formula was used for LV mass calculation based on a thick-wall prolate ellipsoidal geometry (20). To take body size into account, LV mass was indexed for body height (m2.7) as LV mass index (LVMI).
Assessment of covariates
Demographic information were all self-reported or reported by parents or guardians on self-administrated questionnaires, including age at screening, gender, race, smoking status, antihypertensive medicine. All examinations were conducted by trained examiners following rigid protocols. Replicate measurements of height and weight were made, and the mean values were used for analysis. Body mass index (BMI) was used as a measure of obesity. Systolic and diastolic (the fourth Korotkoff phase for children and the fifth Korotkoff phase for adults) blood pressures were recorded using a mercury sphygmomanometer by two trained observers (3 replicates each). The cutoff value of 130 mm Hg was used to define prehypertension and hypertension in the current study. The mean value of the six readings of blood pressure was used for analysis. Plasma high sensitivity c-reactive protein (hsCRP) was measured by latex particle-enhanced immunoturbidimetric assay on the Hitachi 902 Automatic Analyzer. All the information on covariates was collected and validated during the same day when the echocardiography was performed in the clinic examining center.
Statistical analyses
Characteristics of two groups (with and without asthma) were compared using the Student’s t-test (normal distribution) or Kruskal-Wallis test (skewed distribution) for continuous variables, and chi-square test for categorical variables. A multivariate linear mixed model was fitted to the repeated measures of cardiovascular subclinical markers on individuals. Further, we estimated the least-squares means and confidence intervals of outcomes, controlling for age, gender, race, smoking status, antihypertensive medicine, heart rate, hsCRP, BMI, and SBP as fixed effects, as well as individual ID as a random effect. In order to test potential interaction, we categorized age, hsCRP, heart rate, and BMI into three groups, and SBP (<130 and ≥30 mm Hg) into two groups (Table 3), and then included interaction term of asthma and each covariate (considered as both categorical and continuous variables) in the model. Consistent with our previous analyses in the BHS, complete case analysis was used in the current study, and no data imputation was performed. Statistical significance was assessed at the 2-sided α=0.05 level. All data management and analyses were conducted using R version 3.3.0 released on May 3, 2016.
Table 3.
Adjusted means (95% CI) of left ventricular mass by asthma according to demographics and covariates§
| LV Mass, g
|
P for interaction† | LVMI,, g/m2.7
|
P for interaction† | |||
|---|---|---|---|---|---|---|
| Without Asthma (n=1014) | With Asthma (n=104) | Without Asthma (n=1014) | With Asthma (n=104) | |||
| Age, yrs | 0.26 | 0.36 | ||||
| <30 | 136.9 (114.8, 159.1) | 130.8 (105.1, 156.5) | 31.5 (26.2, 36.8) | 30.7 (24.6, 36.9) | ||
| 30~40 | 134.2 (125.1, 143.3) | 133.0 (118.9, 117.0) | 32.8 (30.6, 35.0) | 33.5 (30.1, 36.9) | ||
| ≥40 | 147.7 (139.3, 156.2) | 167.7 (152.0, 183.5) | 35.2 (33.3, 37.2) | 39.8 (36.2, 43.4) | ||
| Race | 0.10 | 0.51 | ||||
| Whites | 150.2 (145.7, 154.7) | 151.5 (142.0, 161.0) | 35.6 (34.6, 36.7) | 37.0 (34.8, 39.1) | ||
| Blacks | 159.3 (152.5, 166.1) | 175.5 (160.0, 191.0) | 39.0 (37.4, 40.5) | 41.8 (38.3, 45.3) | ||
| Gender | 0.42 | 0.20 | ||||
| Male | 181.6 (175.1, 188.1) | 192.2 (178.0, 206.4) | 38.4 (37.1, 39.8) | 41.7 (38.9, 44.6) | ||
| Female | 133.2 (129.0, 137.4) | 137.0 (127.8, 146.3) | 35.5 (34.4, 36.6) | 36.3 (33.9, 38.7) | ||
| Current smoking | 0.94 | 0.80 | ||||
| Yes | 145.4 (138.2, 152.5) | 151.1 (135.2, 167.0) | 35.2 (33.5, 36.8) | 36.7 (33.1, 40.3) | ||
| No | 156.9 (152.8, 161.1) | 162.9 (153.8, 172.1) | 37.4 (36.5, 38.4) | 39.4 (37.3, 41.5) | ||
| Blood Pressure Medication | 0.88 | 0.99 | ||||
| No | 143.1 (140.5, 145.7) | 149.6 (141.5, 157.6) | 34.2 (33.6, 34.8) | 36.2 (34.4, 38.0) | ||
| Missing | 156.9 (153.6, 160.2) | 158.3 (148.9, 167.7) | 37.8 (37.0, 38.5) | 38.7 (36.5, 40.9) | ||
| Yes | 190.3 (181.8, 198.9) | 196.8 (173.9, 219.6) | 46.2 (44.3, 48.1) | 47.9 (42.8, 53.1) | ||
| hsCRP, mg/L# | 0.35 | 0.18 | ||||
| <1.00 | 151.3 (144.8, 157.9) | 162.8 (150.6, 175.0) | 34.8 (33.4, 36.3) | 38.0 (35.3, 40.8) | ||
| 1.00~3.00 | 162.2 (155.6, 168.8) | 164.4 (150.4, 178.3) | 38.8 (37.3, 40.3) | 40.1 (36.9, 43.2) | ||
| ≥3.00 | 147.8 (141.6, 154.1) | 153.6 (139.1, 168.1) | 37.1 (35.6, 38.7) | 38.0 (34.5, 41.4) | ||
| Heart Rate, beats/m | 0.11 | 0.02 | ||||
| Tertile 1 (<65) | 162.6 (156.3, 169.0) | 172.0 (159.4, 184.6) | 38.1 (36.7, 39.5) | 41.8 (39.0, 44.6) | ||
| Tertile 2 (65~72) | 146.1 (139.2, 153.0) | 158.8 (143.5, 174.0) | 35.8 (34.2, 37.3) | 37.6 (34.2, 41.0) | ||
| Tertile 3 (≥72) | 147.8 (142.0, 153.6) | 145.9 (133.2, 158.7) | 35.9 (34.5, 37.3) | 35.6 (32.5, 38.6) | ||
| BMI, kg/m2 | 0.45 | 0.62 | ||||
| <25 | 121.4 (113.1, 129.6) | 122.2 (108.2, 136.2) | 30.2 (28.2, 32.3) | 30.9 (27.4, 34.4) | ||
| 25~30 | 149.4 (142.4, 156.5) | 161.0 (146.3, 175.7) | 34.7 (33.2, 36.3) | 38.1 (34.8, 41.4) | ||
| ≥30 | 181.7 (175.3, 188.0) | 191.9 (178.7, 205.1) | 43.6 (42.2, 45.1) | 46.1 (43.2, 49.1) | ||
| SBP, mm Hg | <0.01 | <0.01 | ||||
| <130 | 149.7 (145.6, 153.8) | 151.9 (143.6, 160.4) | 36.0 (35.1, 37.0) | 37.0 (35.0, 38.9) | ||
| ≥130 | 184.8 (176.2, 193.4) | 224.3 (196.7, 251.9) | 42.8 (41.0, 44.7) | 51.8 (45.8, 57.8) | ||
Stratified analysis was performed according to different groups of each covariate. Mixed regression models were used to adjust for age, gender, race, smoking status, antihypertensive medicine, heart rate, examine survey circles, systolic blood pressure, hsCRP (mg/L), and body mass index as fixed effects, as well as individual ID as random effects. The interaction term of asthma and according to covariate was included in the mixed linear regression models.
hsCRP were measured among 1050 participants (953 and 97 participants without and with a history of asthma, respectively).
The interaction term was built by considering both asthma and covariates as categorical variables.
LV mass, left ventricular mass; LVMI, left ventricular mass index; BMI, Body mass index; SBP, systolic blood pressure; hsCRP, the high-sensitivity C-reactive protein; 95% CI, 95% confidence interval.
Results
With an average 10.4±7.5 years of follow-up, a total number of 2473 follow-up measurements of cardio subclinical markers were collected in 1118 individuals, and 68.6% of them were followed 2 to 4 times (Table 1). In the longitudinal cohort (57.4% in females and 30.7% in blacks), 9.3% were with self-reported asthma, and the mean of age was 27.3±9.6 years of old at baseline. The study variables were compared between two groups (with and without a history of asthma) at both baseline and follow-up. No significant difference was found in gender, race, age, smoking, SBP, heart rate, hsCRP, and blood pressure medication. However, compared with participants without asthma, those with asthma had a longer mean follow-up year (11.0 vs. 9.0, p=0.04) and had a greater average BMI (31.5 vs. 29.9, p=0.04).
Table 1.
Characteristics of the study cohorts by asthma
| Without Asthma (n=1014) | With Asthma (n=104) | P§ | |
|---|---|---|---|
| Baseline† | |||
| Age, yrs | 32.0 (16.0, 35.0) | 27.5 (15.0, 34.0) | <0.01 |
| Female, n (%) | 588 (58.0) | 54 (51.9) | 0.23 |
| Blacks, n (%) | 304 (30.0) | 39 (37.5) | 0.11 |
| Follow-up observations‡, n (%) | 2258 (91.3) | 215 (8.7) | |
| Individuals with # times of follow-ups‡, n (%) | 0.22 | ||
| 1 time | 312 (30.8) | 39 (37.5) | |
| 2 times | 286 (28.2) | 26 (25.0) | |
| 3 times | 290 (28.6) | 32 (30.8) | |
| 4 times | 126 (12.4) | 7 (6.7) | |
| Mean Follow-up, years | 9.0 (5.0, 17.0) | 11.0 (5.2, 18.0) | 0.04 |
| Follow-up† (last measurement) | |||
| Age, yrs | 41.0 (35.1, 45.0) | 39.0 (35.0, 43.3) | 0.06 |
| Current smokers, n (%) | 308 (30.4) | 29 (27.9) | 0.60 |
| BMI, kg/m2 | 29.9 (7.5) | 31.5 (7.6) | 0.04 |
| SBP, mm Hg | 117.0 (14.7) | 118.8 (15.2) | 0.26 |
| Heart Rate, beats per min | 70.3 (9.1) | 69.6 (10.4) | 0.55 |
| hsCRP, mg/L# | 1.32 (0.52, 3.26) | 1.27 (0.55, 3.32) | 0.94 |
| Blood Pressure Medication, n (%) | 0.06 | ||
| Yes | 164 (16.2) | 23 (22.1) | |
| NO | 728 (71.8) | 63 (60.6) | |
| Missing | 122 (12.0) | 18 (17.3) | |
Continuous variables were described as either means (standard deviation) if normal distribution satisfied, or medians (percentile 25th, percentile 75th) if normal distribution unsatisfied.
In the follow-ups, 352 participants were with just one-time follow-up measurement, and the rest of 825 participants were with 2 to 4 repeated follow-up measurements, which added up to a total of 2639 observations.
Two groups’ characteristics were compared using the Student’s t-test or Kruskal-Wallis test for continuous variables, and chi-square test for categorical variables.
hsCRP were measured among 1050 participants (953 and 97 participants without and with a history of asthma, respectively). BMI, Body mass index; SBP, systolic blood pressure.
Table 2 shows the adjusted means of follow-up measurements of LV mass and LVMI in two groups according to the baseline history of asthma. Subjects who had a history of asthma appeared to have a higher adjusted mean of LV mass (169.0 vs. 157.5, p=0.01) and LVMI (41.1 vs. 37.9, p<0.01) during follow-up than those without asthma (Model 1). The significant differences of LV mass and LVMI between these two groups did not appreciably change by introducing additional adjustment for SBP (Model 2) or hsCRP (Model 4). The difference in LV mass was attenuated with further adjustment for BMI (Model 3), SBP (Model 5), and hsCRP (Model 6), while the difference in LVMI remained significant (39.0 vs. 37.2, p=0.03 in Model 3; 39.0 vs. 37.1, p=0.03 in Model 5; 38.4 vs. 36.6, p=0.04 in Model 6).
Table 2.
Adjusted means (95% CI) of left ventricular mass by asthma§
| Without Asthma (n=1014) | With Asthma (n=104) | P | |
|---|---|---|---|
| LV Mass, g | |||
| Model 1 | 157.5 (154.5, 160.5) | 169.0 (160.5, 177.5) | 0.01 |
| Model 2: Model 1 + SBP | 156.9 (154.0, 159.8) | 167.6 (159.5, 175.7) | 0.01 |
| Model 3: Model 1 + BMI | 154.8 (152.2, 157.4) | 160.7 (153.6, 167.8) | 0.11 |
| Model 4: Model 1 + hsCRP | 159.0 (155.0, 163.0) | 171.5 (162.2, 180.8) | <0.01 |
| Model 5: Model 1 + SBP + BMI | 154.5 (151.9, 157.1) | 160.4 (153.4, 167.4) | 0.11 |
| Model 6: Model 1 + SBP + BMI + hsCRP‡ | 152.7 (149.1, 156.4) | 159.4 (151.3, 167.5) | 0.11 |
| LVMI, g/m2.7 | |||
| Model 1 | 37.9 (37.1, 38.6) | 41.1 (39.1, 43.1) | <0.01 |
| Model 2: Model 1 + SBP | 37.7 (37.0, 38.4) | 40.7 (38.9, 42.6) | <0.01 |
| Model 3: Model 1 + BMI | 37.2 (36.6, 37.8) | 39.0 (37.4, 40.7) | 0.03 |
| Model 4: Model 1 + hsCRP | 38.1 (37.2, 39.0) | 41.5 (39.3, 43.6) | <0.01 |
| Model 5: Model 1 + SBP + BMI | 37.1 (36.5, 37.7) | 39.0 (37.4, 40.6) | 0.03 |
| Model 6: Model 1 + SBP + BMI + hsCRP‡ | 36.6 (35.7, 37.4) | 38.4 (36.6, 40.3) | 0.04 |
Mixed regression models were used to adjust for age, gender (male/female), race (black/white), smoking status (current smokers/non-current smokers), antihypertensive medicine (Yes/No/Missing, using “No” as reference), and heart rate (beats per min), and examine survey circles as fixed effects, as well as individual ID as random effects.
hsCRP were measured among 1050 participants (953 and 97 participants without and with a history of asthma, respectively).
LV mass, left ventricular mass; LVMI, left ventricular mass index; BMI, Body mass index; SBP, systolic blood pressure; hsCRP, the high-sensitivity C-reactive protein; 95% CI, 95% confidence interval.
We then performed stratified analyses by covariate categories (Table 3). We found that SBP significantly modified the association of asthma with LV mass and LVMI (P for interaction<0.01). For participants whose SBP were of 130 mm Hg and over (prehypertension and hypertension), we found significant differences of LV mass between asthma and non-asthma group (adjusted means: 224.3 vs. 184.8; and regression coefficient (β):=39.5, p=<0.01) and LVMI (adjusted means: 51.8 vs. 42.8, β=9.0, p<0.01) (Figure 1). Among normotensive subjects (SBP < 130 mm Hg), the difference in LV mass was not significant between two groups (adjusted means: 151.9 vs. 149.7, β=2.2, p=0.60 for LV mass; 37.0 vs. 36.0, β=0.9, p=0.33 for LVMI). There were no significant interactions between asthma and age, race, gender, blood pressure medication, BMI or hsCRP with respect to the follow-up measures of LV mass and LVMI.
Figure 1. Interaction of asthma with SBP on left ventricular mass.
Adjusted means and 95% confident intervals of heart subclinical biomarkers were calculated using mixed regression models. Models controlled for age, gender (male/female), race (black/white), smoking status (current smokers/non-current smokers), antihypertensive medicine (Yes/No/Missing, using “No” as reference), and heart rate (beats per min), hsCRP (mg/L), and examine survey circles as fixed effects, as well as individual ID as random effects. β was the regression coefficient of asthma in stratified SBP level or smoking status groups, followed by its p values for statistical significance. P for interaction term was given by including the interaction term in the mixed model.)
Discussion
In this prospective cohort of an average ten-year follow-up, we found that adults with a history of asthma from childhood had a significantly greater LVMI compared with those without asthma, independent of major CVD risk factors including age, gender, race, smoking status, antihypertensive medicine, hsCRP, heart rate, BMI, and SBP. Unique to this study was our finding that a history of asthma from childhood appeared to associate with increased risk for elevated LVMI among apparently healthy young adults. In addition, we found significant interactions between asthma and SBP on LV mass and LVMI; the associations between asthma and LVMI appeared to be stronger among participants with higher SBP (prehypertension and hypertension) than those with lower SBP.
To the best of our knowledge, the current study is the first to prospectively analyze associations between a history of asthma from childhood and LV mass in adulthood, a prominent indicator of target-organ damage. Our findings were consistent with previous studies in which asthma was related to other cardiovascular subclinical markers reflecting arterial stiffness in adults, such as carotid artery intima-media thickness (21) and pulse wave velocity (22). In addition, previous observational studies also showed that asthmatic subjects had increased the risk of major cardiovascular diseases and death. In a prospective cohort of 203,595 adults, asthma was associated with a 40% increase in coronary heart disease (CHD), a 20% increase in cerebrovascular disease, an 114% increase in heart failure, and a 228% increase in all-cause mortality (13). Similarly, a 2-fold increase risk of incident CHD and stroke due to asthma was observed in the Atherosclerosis Risk In Communities Study (23).
Our data suggested that asthma was independently associated with increased LVMI, but the mechanisms underlying this epidemiological association remain unclear. Previous evidence emphasized the role of systemic inflammation in the relation between asthma and CV disorders, given that a higher level of inflammatory markers (e.g. hsCRP, interleukin, leukotrienes, and fibrinogen) in asthmatic subjects might affect myocardial inflammation and remodeling (6), which in turn contribute to LV hypertrophy and later heart failure (7). Supported by the current study, we observed one unit increase of hsCRP was significantly associated with 1.40 and 0.40 increase in LV mass and LVMI (Model 4 in Table 2). However, additional adjustment of hsCRP didn’t attenuate the positive association between asthma and LVMI. Similarly, a prospective cohort study showed a 1.59 fold risk of incident CVD events associated with asthma, which wasn’t significant attenuated by additional control for systemic inflammatory markers (24). Therefore, except for chronic inflammatory pathophysiologies, it suggested other pathogenesis mechanisms might be involved. For example, pulmonary function decline in asthmatics could be another potential pathway (25,26). Asthmatic airway hyperresponsiveness is a trigger for the compensatory hypertrophic growth of myocardial cells, and result in increased LV wall thickness, LV mass, cardiac output, and diastolic dysfunction (27). In asthmatics, lung hyperinflation and elevated negative intrathoracic pressure may directly increase LV transmural pressure and augments LV wall, and indirectly affect LV structure or function through the right ventricular dysfunction because of the cardiac chamber interdependence (28,29). Evidence from both epidemiological and experimental studies showed that pulmonary hyperinflation was associated with greater LV mass (26) and reduced LV filling (30). Furthermore, a pharmacological mechanism has been also posted, linking asthma medications (e.g. oral corticosteroids and inhaled β2 agonists) with increased CVD events and death (31,32). In addition, asthmatics were found to be more physically inactive, obese, and hypertensive (33), and more predisposed to diabetes, chronic obstructive pulmonary disease, and arthritis (34) compared with the normal, and these risk factors might also affect LV hypertrophy.
Intriguingly, we found significant interactions between asthma and SBP on increased LV mass and LVMI—the associations were stronger among those with prehypertension and hypertension. Although the precise mechanisms remain unclear, such interactions are biologically plausible. First, the interaction between hypertension and inflammation has been documented on vascular biology (e.g. vascular cells activation and arterial structural changes) and CVD events (35). Second, activation of trophic factors on LV hypertrophy could be triggered synergistically by both asthma and elevated blood pressure through the sympathetic nervous system and the renin-angiotensin–aldosterone (RRA) system (36,37). For instance, an increased level of circulating aldosterone and angiotensin II due to hypertension and acute asthma would lead to myocardial fibrosis and promote myocyte cell growth (38,39). Further, medications for asthma and hypertension might amplify the adverse effects of each condition on LV mass (40,41).
In the current study, we used a community-based longitudinal cohort to assess the associations between a history of asthma from childhood and LV mass among asymptomatic young adults. The major strengths of our study include prospective design, long follow-up period, and a mixed model for repeated LV echocardiographic measurements and covariates. Additionally, availability of various and high-quality individual data enabled us to control for potentially important confounders and examine possible interaction between asthma and traditional CVD risk factors. Even though, several limitations merit discussion. First, information about the history of asthma was collected through questionnaires rather than clinical records. Second, a small proportion (15%) of records were followed less than one year from baseline. However, the results were similar in sensitivity analysis by excluding those with short follow-up period. Third, although we had carefully controlled for covariates in the analyses, information on some potential confounders was unavailable (such as baseline LV measurement, asthma severity, frequency of inhalator and other medication use, frequency of hospitalization or ER visits for asthma, and pulmonary function), making us unable to control for their influence on the associations. Considering multiple comparisons were performed in testing interactions with risk factors, we could not exclude the possibility that the observed interaction between SBP and asthma might be due to chance. However, the observed interaction (p=0.002 and 0.003 for LV mass and LVMI, respectively) remained significant even after Bonferroni correction (p=0.006). Further investigations are warranted to validate this finding.
In summary, our results indicated that young adults with a history of asthma were at a significantly greater risk of increased LVMI, independent of other major CVD risk factors. Additionally, the positive association of asthma with LV mass and LVMI were more prominent among participants with prehypertension and hypertension. Our data suggest aggressive lifestyle modifications or even pharmacologic treatment may be applied to people with a history of asthma, especially those also affected by high blood pressure, to lower cardiovascular risk. Further studies are warranted to verify our findings in other cohorts.
PERSPECTIVES.
COMPETENCY IN MEDICAL KNOWLEDGE
Young adults with a history of asthma from childhood had a significantly greater left ventricular mass index (LVMI) in adulthood compared with those without asthma, independent of major cardiovascular disease risk factors. Furthermore, significant interactions between asthma and elevated systolic blood pressure were observed on increased left ventricular (LV) mass and LVMI. Special cardiovascular surveillance should be targeted in asthmatics, and optimized lifestyle management and pharmacologic treatment were needed for hypertensive-asthmatic patients.
TRANSLATIONAL OUTLOOK
A history of asthma from childhood is associated with higher LVMI, especially among participants with prehypertension and hypertension.
Abbreviations list (in alphabetical order)
- BMI
body mass index
- hsCRP
the high-sensitivity C-reactive protein
- LV Mass
left ventricular mass
- LVMI
left ventricular mass index
- SBP
systolic blood pressure
Footnotes
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