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. Author manuscript; available in PMC: 2013 Feb 1.
Published in final edited form as: Hypertension. 2011 Dec 27;59(2):219–225. doi: 10.1161/HYPERTENSIONAHA.111.184101

Rate of decline of forced vital capacity predicts future arterial hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

David R Jacobs Jr 1, Hiroshi Yatsuya 2, Mary O Hearst 3, Bharat Thyagarajan 4, Ravi Kalhan 5, Sharon Rosenberg 6, Lewis J Smith 7, R Graham Barr 8, Daniel A Duprez 9,10
PMCID: PMC3269403  NIHMSID: NIHMS346411  PMID: 22203738

Abstract

Lung function studies in middle-aged subjects predict cardiovascular disease (CVD) mortality. We studied if greater loss of forced vital capacity (FVC) early in life predicted incident hypertension (HTN). The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) study examined between 1985-86 (CARDIA year 0, ages 18-30 years) and 2005-06 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios (HR) and linear regression models predicted incident HTN at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 – peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5 and 10). Covariates included demographics, center, systolic blood pressure, FVC max, smoking, physical activity, asthma and BMI. Unadjusted cumulative incident HTN was 25% in the lowest FVC loss quartile (Q1, median loss=370ml) compared to 12% cumulative incident HTN in those who achieved peak FVC at year 10 (Q4). Minimally adjusted HR for Q1 vs. Q4 was 2.21 (95% CI: 1.73-2.83) and this association remained significant in the fully adjusted model (1.37, 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality.

Keywords: forced vital capacity, hypertension, CARDIA, adults, cohort

As early as the 1960’s, lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) was found to be associated with all cause and cardiovascular disease (CVD) death even in the absence of overt respiratory symptoms or disease.1,2 The association between lung function and CVD death has been consistently observed.3-8 Typical of these studies, Hole et al.3 reported on 15,411 middle-aged men and women beginning in 1972-76 and followed for 15 years. Relative risk for all cause and ischemic heart disease death was inversely graded across FEV1 levels. Specifically comparing the highest FEV1 quintile as reference to the low normal third quintile of FEV1 (men 87-96%, women 90-100% of predicted FEV1), all cause death relative risks were 1.45 (95% confidence interval 1.26 to 1.68) in men and 1.21 (1.03 to 1.42) in women, with qualitatively similar findings for ischemic heart disease death. However, lung function did not predict nonfatal myocardial infarction in the Copenhagen City Heart Study.6,7 The Malmö Preventive Project found an association of a decline in FVC and FEV1 with heart failure (ischemic and non-ischemic) in 20,998 CVD-free men follow-up for 23 years, while there was little association with FEV1/FVC, the latter restricted to smokers.8

Hypertension is a major cause of development of heart failure without preceding myocardial infarction. Reports have shown inverse cross-sectional associations between lung function measures (especially FVC and FEV1 but not FEV1/FVC) and blood pressure;5,9,10 however, analyses have been inconsistent.9,11 On the contrary, cohort studies have shown that lower lung function measures at baseline were consistently associated with higher incidence of subsequent hypertension,9,11,12 suggesting more rapid blood pressure elevation in persons who initially have lower lung function. This study aimed to assess whether steeper decline in lung function, even within the normal range, is associated with higher incidence of hypertension statistically controlling for level of baseline lung function. We hypothesized that greater rate of loss of lung function would predict future arterial hypertension in a general sample of young blacks and whites.

MATERIALS AND METHODS

The Coronary Artery Risk Development in Young Adults

The CARDIA study is a prospective epidemiological study of the evolution of CVD risk factors in young adults.13 Briefly, from 1985 to 1986, 5,115 black and white individuals aged 18–30 years were examined in Birmingham, AL; Chicago, IL; Minneapolis, MM; and Oakland, CA, USA. At the Birmingham, Minneapolis, and Chicago sites, participants were randomly selected from total communities or from specific census tracts. In Oakland, participants were randomly selected from the Kaiser Permanente Medical Care Program membership. Recruitment achieved nearly equal numbers at each site of race, sex, education (more than high school, high school of less), and age (18–24 years, 25–30 years). Fifty percent of invited individuals contacted were examined (47% blacks and 60% of whites) and became the CARDIA cohort. Reexamination occurred after 2, 5, 7, 10, 15, and 20 years.

Lung function

Lung function was measured at years 0, 2, 5, and 10 using a Collins Survey 8-liter water sealed spirometer and an Eagle II Microprocessor (Warren E. Collins, Inc., Braintree, MA). At year 20, a dry rolling-seal OMI spirometer was used (Viasys Corp, Loma Linda, CA). A comparability study performed on 25 volunteers at the LDS Hospital (Salt Lake City, UT) demonstrated excellent consistency between the old and new machines; the average difference between the Collins Survey and OMI spirometer was 6 ml for FVC and 21 ml for FEV1. Standard procedures of the American Thoracic Society were followed at all examinations.14-17 Daily checks for leaks, volume calibration with a 3-liter syringe and weekly calibration in the 4–7 liter range were undertaken to minimize methodological artifacts between exams. We analyzed FVC and FEV1 as the maximum of five satisfactory maneuvers. In almost all cases, the maximum and second highest maneuvers agreed to within 150 ml.

Considering the young age of some participants at baseline, the possibility that lung function was not yet reached the maximum at year 0, and the available data, we estimated an individual’s peak lung function as the maximum attained at year 0, 2, 5, or 10. This value was usually the highest achieved among the CARDIA measurements, since only 4% (138 /3426 of participants who had at least one FVC among years 0, 2, 5, and 10 and also had FVC measured at year 20) had their highest value at year 20, and in only 1.6% (55) was the year 20 the greatest by more than 100 mL. Change in lung function was calculated as from peak lung function minus year 10 lung function. We divided participants into approximate quartile by this change of FVC from peak: ≤−250 mL, -249 mL to -100 mL, -99 mL to -1 mL, and exactly 0 mL.

Hypertension

Blood pressure was measured on the seated participant’s right arm after a 5-minute rest at each examination, using a Hawksley random zero sphygmomanometer (W. A. Baum Company, Copiague, New York) at baseline through year 15, and using a digital BP monitor (Omron HEM-907XL; Online Fitness, Santa Monica, California) at the year 20 follow-up examination. A calibration study was performed, and values calibrated to the sphygmomanometric measures were used for the year 20 follow-up measurements so that essentially no machine bias remained (please see http://hyper.ahajournals.org.): CS= 3.74 +0.96*OS and CD = 1.30+0.97*OD where CS is calibrated systolic blood pressure, CD is calibrated diastolic blood pressure, OS is observed Omron systolic blood pressure and OD is observed Omron diastolic blood pressure. Three measurements were taken at 1-minute intervals. Systolic and diastolic pressures were recorded as phase I and phase V Korotkoff sounds. The average of the second and third measurements was the pressure of record. We defined hypertension, consistent with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or taking antihypertensive medication at that examination.18 Individuals free of hypertension at years 0, 2, 5, 7 and 10 were considered to have incident hypertension if they met one of the three criteria at either year 15 or 20.

Other variables

Body weight was measured in light clothing to the nearest 0.1 kg with a calibrated balance beam scale, and height without shoes was measured to the nearest 0.5 cm using a vertical ruler. Body mass index (BMI) was computed as weight divided by height squared (kg/m2). Smoking status was classified as never, past or current smoker. Physical activity was measured using an interviewer-administered questionnaire19 concerning the frequency of participation in 13 different activities during the past 12 months. Because participants were not asked specifically about duration of physical activity bouts, exact energy expenditure cannot be estimated and the activity is expressed approximately in “Exercise Units” (EU). We considered physician-confirmed asthma to be present from the time of the first examination in which the subject either was taking asthma medication (usually based on examination of medicine containers) or provided a positive response to “Has a doctor or nurse ever said that you have asthma?”

Exclusions

In the present study, we first restricted the study sample to those with lung function measurements at year 10 and a value for peak lung function (n=3,754). We excluded 68 participants for missing information on covariates (height, body mass index, smoking status, physical activity, systolic blood pressure all at year 10). We further excluded 41 subjects with physiologically implausible level of FVC change (-1L or more decrease). Finally, participants who were ever classified as hypertensive through year 10 examination (n=440) were excluded, leaving 3,205 for the present analyses.

Statistical analysis

Age-, sex-, race- and center-adjusted means and proportions among FVC change quartiles were calculated and tested by a general linear model. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs) for incident hypertension in relation to quartiles of FVC change, beginning with a minimally adjusted model (age, sex, race, height, center, and education level), followed by an adjusted model with behavioral variables (physical activity, smoking) and systolic blood pressure at year 10, peak FVC and history of asthma covariates. Time of occurrence of incident hypertension was taken to be the CARDIA examination year for those diagnosed by high blood pressure; or else the previous year for those defined by use of medication. We also ran models that explored BMI as a common mechanism for changes in lung function and blood pressure. These models included year 10 BMI as a covariate in analyses using FVC loss through year 10 as the predictor of interest, or year 20 BMI as a covariate in analyses using FVC loss through year 20 as the predictor of interest. We considered alterations in the coefficients for lung function loss by addition of BMI to the model to go beyond deconfounding, because those altered coefficients discount the potential importance of unmeasured variables that are in the causal pathway linking BMI to both lung function and hypertension. Parallel analyses were conducted using FEV1 and FEV1/FVC instead of FVC. We also did several sensitivity analyses. Since the exclusion of those with physiologically implausible lung function change used rather arbitrary cutpoints, we carried out sensitivity analyses adding participants with FVC change more than 1L but ≤1.5 L (n=3,228) or deleting participants with FVC change ≥0.5L (n=2,999). The hazard proportionality assumption was ascertained graphically by examining whether the ln(-ln) survival curves were parallel by visual inspection. Second, we assessed robustness of the estimates by testing hierarchical models adding in changes from year 5 in BMI and waist circumference and pack years of cigarette smoking. Finally, we included diastolic blood pressure, heart rate and systolic blood pressure at baseline and year 10. All statistical analyses were performed by SAS v9.2 of the SAS System for Windows, and statistical significance was evaluated at p-value <0.05.

RESULTS

The study sample was (mean (standard deviation) 34.9 (3.7) years old at year 10, 56% female, and 55% whites. Mean FVC at year 10 was 4.46 (1.02) L. Peak FVC was achieved at age 29.4 (4.62) years, with 27% of the sample achieving peak FVC at year 0, 18% at year 2, 27% at year 5 and 28% at year 10. Individuals who reached peak at year 10 experienced lung function decline from year 10 to 20 (mean decline: -422±352 mL). On average, participants lost 159 (185) mL of FVC from peak to year 10. Although those in the greatest FVC loss category (Q1) lost a median of 370 mL from their maximum attained value, they remained well within the normal range of FVC (Table 1). Those in the greatest loss category were more likely to be male, older, less physically active, a current smoker, higher BMI and higher systolic blood pressure at year 10.

Table 1.

Means and standard deviations or percentages according to quartiles of FVC change from peak to year 10, CARDIA, 1995-96 (n=3,205)

Year 10 characteristics Quartile of FVC change from peak to year 10
P value*
Q1 (n=787) Q2 (n=811) Q3 (n=666) Q4 (n=941)
Range (mL) -980 to -250 -249 to -100 -99 to -1 0
Median (mL) -370 -170 -60 0
Female 41.6% 54.8% 63.5% 64.0% <.0001
White 54.5% 56.7% 52.9% 54.9% 0.52
Center
 Birmingham 28.1% 24.2% 17.7% 19.2% <.0001
 Chicago 17.0% 23.1% 25.5% 24.9%
 Minneapolis 34.9% 28.1% 27.5% 23.0%
 Oakland 20.0% 24.7% 29.3% 32.9%
Age (y) 35.8 (3.4) 35.5 (3.5) 34.6 (3.6) 33.8 (3.7) <.0001
Education (y) 15.4 (0.1) 15.4 (0.1) 15.7 (0.1) 15.5 (0.1) 0.15
Height (cm) 170.5 (0.3) 170.2 (0.2) 169.9 (0.3) 170.4 (0.2) 0.41
Body mass index (kg/m2) 30.7 (0.2) 27.3 (0.2) 25.7 (0.2) 24.4 (0.2) <.0001
ΔBody mass index, year 10 – year of peak FVC (kg/m2) 1.94 (0.16) 2.11 (0.15) 2.02 (0.16) 2.52 (0.14) 0.03
ΔBody mass index, year 20 – year 10 (kg/m2) 3.95 (0.09) 2.49 (0.09) 1.69 (0.10) -0.08 (0.09) <.0001
Systolic blood pressure (mmHg) 110.0 (0.3) 107.4 (0.3) 106.3 (0.4) 106.4 (0.3) <.0001
Physical activity (Exercise Units)† 308 (10) 324 (9) 352 (10) 367 (9) <.0001
Smoking status
 Current smoker 29.2% 25.8% 20.0% 20.8% <.0001
 Past smoker 14.0% 15.9% 17.1% 19.0% 0.052
Asthma reported by year 10‡ 14.3% 10.8% 8.8% 9.4% 0.004
Peak FVC (L) 4.52 (0.02) 4.41 (0.02) 4.39 (0.02) 4.48 (0.02) 0.0002
Year 10 FVC (L) 4.10 (0.02) 4.24 (0.02) 4.34 (0.02) 4.48 (0.02) <.0001
Year 10 FVC (% predicted) 97.5 (11.6) 101.3 (11.5) 104.1 (11.6) 107.2 (11.9) <.0001
Cumulative hypertension incidence by year 20§ 24.8% 15.4% 12.2% 12.3% <.0001
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FVC denotes forced vital capacity. Peak is the highest FVC among whatever measurements were available at years 0, 2, 5, and 10 (participants were 18-30 years old at year 0, average 25 years old).

*

P values were derived from chi-squared test for sex, race and center, and one-way analysis of variance for age. General linear model adjusted for age, sex, race, and center was used to derive adjusted means, proportions, and p-values (with 3 degree of freedom).

†

Physical activity was measured using an interviewer-administered questionnaire concerning the frequency of participation in 13 different activities during the past 12 months.

‡

At least one self-report of physician-confirmed asthma that was still active at the time of interview or history of medication use at year 0, 2, 7, or 10.

§

Incident hypertension was defined when systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg, or use of antihypertensive medication was reported at either year 15 or 20.

During follow-up through year 20, hypertension developed in 508 cases (incidence density: 8.6 per 1,000 person-years). Incidence density was more than two-fold in subjects with largest FVC loss (Q1) compared to Q4 (13.9 vs. 6.1 per 1,000 person years) (Table 2). In the minimally-adjusted model, HR for subjects in Q1 compared to Q4 was 2.21. Adjustment for confounders somewhat attenuated the magnitude of the association (HR for those in Q1 vs. Q4 in model 2: 1.76). Adjustment for BMI further attenuated this association (HR: 1.37).

Table 2.

Multivariable analysis of incident hypertension (after year 10) related to Forced Vital Capacity (FVC) Change from its peak to year 10, CARDIA, 1995-2006 (n=3,205)

Analysis Quartile of FVC change from its peak to year 10 Continuous FVC change from its peak to year 10
Q1 (n=787) Q2 (n=811) Q3 (n=666) Q4 (n=941)
Range (mL) -980 to -250 -249 to -100 -99 to -1 0
Median (mL) -370 -170 -60 0
Number of cases 197 125 79 107
Incidence density/1,000 person years 13.9 8.4 6.4 6.1
Model 1 2.21 (1.73-2.83)* 1.30 (1.00-1.69) 1.03 (0.77-1.38) 1 (reference) 1.32 (1.22-1.42)†
Model 2 1.75 (1.36-2.25) 1.18 (0.90-1.53) 1.00 (0.74-1.33) 1 (reference) 1.24 (1.15-1.34)
Model 3 1.37 (1.05-1.80) 1.03 (0.79-1.35) 0.95 (0.71-1.27) 1 (reference) 1.15 (1.06-1.26)
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*

Hazard ratio (95% confidence interval).

†

Hazard ratio (95% confidence interval) per 1 standard deviation (223 mL) decrement of FVC change from peak to year 10.

Model 1: Adjusted for age, sex, race, height, center, and education level, all measured at baseline

Model 2: Model 1 plus covariates systolic blood pressure at year 10, maximum FVC achieved either at year 0, 2, 5 or 10 exam, smoking (never, past, current) (year 10), physical activity (year 10), and history of asthma (year 10).

Model 3: Model 2 further adjusted for body mass index (year 10).

The association between FVC loss from peak through year 20 (which included the period during which hypertension developed) and the 456 incident hypertension cases (Table 3) was stronger than the corresponding association using FVC change from peak through year 10 (Table 2). Analysis using FEV1 instead of FVC yielded similar results (data not shown), not surprisingly given that the correlation of FEV1 with FVC was 0.94 at both year 10 and year 20. Changes in the ratio FEV1/FVC were not predictive of future hypertension (data not shown).

Table 3.

Multivariable analysis of incident hypertension (after year 10) related to Forced Vital Capacity FVC Change from its peak to year 20, CARDIA, 1995-2006 (n=2,580)

Analysis Quartile of FVC change from its peak to year 20 Continuous FVC change from its peak to year 20
Q1 (n=645) Q2 (n=645) Q3 (n=646) Q4 (n=644)
Range (mL) -3110 to -740 -739 to -503 -502 to -291 -290 to +1450
Median (mL) -938 -605 -389 -145
Number of cases 162 130 95 69
Incidence density/1,000 person years 13.0 10.3 7.5 5.4
Model 1 2.67 (1.96-3.64)* 1.97 (1.46-2.67) 1.37 (1.00-1.88) 1 (reference) 1.41 (1.31-1.52)†
Model 2 1.98 (1.44-2.72) 1.50 (1.10-2.03) 1.16 (0.85-1.59) 1 (reference) 1.37 (1.25-1.50)
Model 3 1.49 (1.07-2.07) 1.24 (0.91-1.70) 1.03 (0.75-1.42) 1 (reference) 1.28 (1.16-1.42)
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*

Hazard ratio (95% confidence interval)

†

Hazard ratio (95% confidence interval) per 1 standard deviation (398 mL) decrement of FVC change from peak to year 20.

Model 1: Adjusted for age, sex, race, height, center, and education level

Model 2: Model 1 plus covariates systolic blood pressure at year 10, maximum FVC achieved either at year 0, 2, 5 or 10 exam, smoking (never, past, current) (year 20), physical activity (year 20), and history of asthma (year 20),

Model 3: Model 2 further adjusted for body mass index (year 20).

Three sensitivity analyses were employed. 1) Changing the cut-points for the initial exclusion level of peak to year 10 FVC change either to 1.5L or 0.5L yielded similar results, with HR in the fully adjusted models for 223 mL decrease in FVC: 1.07, 95% CI: 0.97-1.17 and 1.09, 95% CI: 1.01-1.19, respectively. 2) We reversed dependent and independent variables and found that neither systolic blood pressure at year 5 nor its change through year 10 predicted FVC change from year 10 through year 20 (data not shown). Thus the direction of association was specific for lung function change predicting hypertension. 3) The addition of pack years, changes in BMI or waist circumference, diastolic blood pressure, or earlier measures of blood pressure did not substantively change the original findings.

DISCUSSION

In this study of black and white American adults of the CARDIA Study, FVC change from peak to year 10 significantly predicted incidence of arterial hypertension during the 10-year follow-up (CARDIA years 10 to 20). The association was robust to adjustment and sensitivity analysis. These findings were consistent with previous studies that found that inter-individual variation in lung function level in early adulthood to be associated with future development of hypertension.9,11,12 Our study extended this previous understanding of association between inter-individual differences in lung function and hypertension to include intra-individual change of lung function from peak and hypertension in a generally healthy sample. Lung function deterioration can be seen as an independent factor associated with future hypertension incidence, even for those with low normal lung function.

Although the relationship between reduced FVC and FEV1 and the incidence of hypertension is clear, the mechanisms underlying these associations are less clear. We present several speculations and hypotheses which may help to focus future research. In the normal lung, once peak lung function is achieved, the changes leading to decreased elastic recoil of the lung include enlargement of airspaces (emphysema) and resultant loss of supporting tissue for peripheral airways.20 There may also be small airway narrowing independent of emphysema.21-23 These changes probably underlie the moderate loss from peak that we observed in the quartile with the most FVC loss from peak through CARDIA year 10 (Table 1). In an attempt to understand why reduced FVC and FEV1 predisposed to heart failure, while reduced FEV1/FVC did not, Engström8 pointed to a decline in lung volume or reduced compliance of the lung tissue or chest wall, rather than to airway obstruction. Our findings are in agreement with this view. Furthermore, the age-related reduction of lung elastic recoil is associated with a reduction in vital capacity.24 Although FEV1 is more specifically affected by elastic recoil than is FVC, in our young, healthy sample FEV1 and FVC are highly correlated and statistically nearly interchangeable; thus we cannot distinguish loss of elastic recoil from other causes of loss of lung volume within our data. The loss of lung elastic recoil could be paralleled by a non-atherosclerotic reduction in vascular elasticity. A decrease in arterial elasticity will result in an increase in arterial blood pressure.25

In addition there may be reduced chest wall compliance and decreased respiratory muscle strength, even without decline in elastic recoil.20 It is of particular interest in this regard that adjustment for BMI substantially attenuated the association between decline of lung function and increase in blood pressure. As a common pathology might result from excess BMI to both decrease FVC and increase blood pressure, adjustment for BMI may discount any such factors that participate in this common pathology. Restrictive processes beyond physical restriction from impaired diaphragmatic motion, likely play a role in loss of lung function with increasing central adiposity.26 For example, reduced lung function is associated with diabetes and insulin resistance. Engström et al.27 studied the relationship between FVC at baseline and the incidence of diabetes and insulin resistance in a follow-up exam after about 12 years. After the follow-up examination, subjects with a moderately reduced FVC had an increased risk of developing insulin resistance and diabetes. It is well known that increases in both BMI and insulin resistance lead to a higher blood pressure.

Inflammation is also associated with reduced lung function. Epidemiological studies report associations between reduced lung function and increased levels of markers of inflammation in healthy subjects.28-31 Inflammation will also affect the arterial system. We previously demonstrated in asymptomatic subjects that hs-CRP is associated with increased arterial stiffness.32

Other possibilities exist related to remodeling of the airway beyond that caused by inflammatory processes in the lung. External and environmental elements together with complex genetic factors propagate inflammation.33 This leads to active participation of structural elements, such as the airway epithelium and smooth muscle.34-36 Inflammation can occur in both the pulmonary and general vasculature and will aggravate endothelial dysfunction. Endothelial dysfunction leads to changes in arterial function, which in turn leads to vascular remodeling. Giannotti et al. noted that in vivo endothelial repair capacity of early endothelial progenitor cells is reduced in patients with prehypertension and hypertension.37 Endothelial progenitor cell senescence and impaired endothelial function likely represent early events in the development of hypertension. In the Multi-Ethnic Study of Atherosclerosis (MESA) study, a population-based study of an older cohort free of overt CVD at baseline, we described that structural and functional vascular abnormalities were independent predictors of incident hypertension.25 These findings are important for understanding the pathogenesis of arterial hypertension. Thus it may be that the decline in lung function and the development of essential hypertension develop in parallel along a common pathophysiological pathway involving both functional and structural changes. Of note, changes in lung function predicted incident hypertension, but changes in blood pressure did not predict loss of lung function.

Increased blood pressure variability is associated with higher cardiovascular risk, as noted also by Engström.8 There is limited information regarding the association of lung function and blood pressure variability. In a population-based study, low FVC and FEV1 was associated with short-term systolic blood pressure variability.38 It is suggested that high beat-to-beat variability in blood pressure could contribute to the increased cardiovascular risk in subjects with moderately reduced FEV1. Further studies are necessary to explore the effect of the autonomic nervous system on lung function over time and the impact on blood pressure level and its variability over time.

Hypoxia as a potential trigger for the incident hypertension is improbable because these subjects had only a small decline in lung function over time, which was within normal limits, even when the lung function from peak through year 20 was considered.

There were several limitations of this study. As in all observational studies, unmeasured and residual confounding could be a problem. Loss to follow-up by year 20 was greater in black participants and current smokers, potentially distorting any observed association. There are limitations to our estimate of peak FVC since measurement of lung function only occurred at years 0, 2, 5, 10 and 20. It is possible that the actual peak occurred between measurement years and a few participants peaked after year 10. These sources of within person variation would likely be non-differential and tend to attenuate the observed associations. Although age at achievement of peak FVC is less critical to our argument, it would be less well estimated given an FVC plateau, small variations in lung function on repeat testing, and the fact that many participants may have reached peak before the year 0 examination. The strengths of the present analysis, besides its novelty in the study design, are that large numbers of generally healthy participants consisting of both blacks and whites and women and men had repeated measurements of high-quality spirometry data, and excellent retention of the original cohort. The directional specificity of the association from lung function change to incident hypertension was strengthened by a sensitivity analysis in which change in blood pressure did not predict future lung function. The ability to identify the end of lung maturation and lung function decline soon thereafter was an additional strength of the study design.

Perspectives

Early detection of hypertension is a major diagnostic step in the scope of preventing future CVD. Unfortunately CVD preventive assessment is started after the age of 40 years. With the major health-economic burden of non-communicable diseases, it is important to consider prevention and early detection from a broader perspective. Our findings clearly demonstrated that spirometry, an easy and inexpensive test, can facilitate the prediction of hypertension in young apparently healthy individuals when there is a slight decline to a low normal lung function. Given the interconnectedness of the lung and cardiovascular system, future research should explore the common pathways between changes in lung function and vascular behavior to improve the health of both systems.

Supplementary Material

1

Acknowledgments

Sources of Funding This research was supported by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, and N01-HC-48050 from the National Heart, Lung, and Blood Institute, National Institutes of Health. Pulmonary Reading Center at year 20 was at Latter Day Saints Hospital, Salt Lake City, Utah, funded by subcontract PF-HC95095 to the CARDIA Coordinating Center.

Footnotes

Disclosures D.R.J., H.Y., S.R., M.O.S., B.T., L.J.S, R.G.B., D.A.D. have no conflict of interest to declare.

R.K. is a consultant for Forest Laboratories and a consultant for Boehringer-Ingelheim.

Contributor Information

David R. Jacobs, Jr., Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis

Hiroshi Yatsuya, Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine.

Mary O. Hearst, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis

Bharat Thyagarajan, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.

Ravi Kalhan, Department of Medicine, Asthma-COPD Program, Northwestern University, Chicago, IL.

Sharon Rosenberg, Department of Medicine, Asthma-COPD Program, Northwestern University, Chicago, IL.

Lewis J. Smith, Department of Medicine, Asthma-COPD Program, Northwestern University, Chicago, IL

R. Graham Barr, Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY.

Daniel A. Duprez, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis Department of Medicine, Cardiovascular Division, University of Minnesota.

References

  1. Dawber TR, Kannel WE, Friedman GD. Vital capacity, physical activity and coronary heart disease. In: Roab W, editor. Prevention of ischemic heart disease: principles and practice. Springfield, IL: Charles C. Thomas Publisher Ltd.; 1966. pp. 254–265. [Google Scholar]
  2. Higgins MW, Keller JB. Predictors of mortality in the adult population of Tecumseh. Arch Environ Health. 1970;21:418–424. doi: 10.1080/00039896.1970.10667260. [DOI] [PubMed] [Google Scholar]
  3. Hole DJ, Watt GC, Davey-Smith G, Hart CL, Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ. 1996;313:711–716. doi: 10.1136/bmj.313.7059.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Schünemann HJ, Dorn J, Grant BJ, Winkelstein W, Jr, Trevisan M. Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study. Chest. 2000;118:656–664. doi: 10.1378/chest.118.3.656. [DOI] [PubMed] [Google Scholar]
  5. Hozawa A, Billings JL, Shahar E, Ohira T, Rosamond WD, Folsom AR. Lung function and ischemic stroke incidence: the Atherosclerosis Risk in Communities study. Chest. 2006;130:1642–1649. doi: 10.1378/chest.130.6.1642. [DOI] [PubMed] [Google Scholar]
  6. Vestbo J, Lange P. Forced expiratory volume in 1 second (FEV1)--a respiratory physiological measurement of considerable prognostic value. Ugeskr Laeger. 1991;153:2292–2295. in Danish. [PubMed] [Google Scholar]
  7. Lange P, Nyboe J, Jensen G, Schnohr P, Appleyard M. Ventilatory function impairment and risk of cardiovascular death and of fatal or non-fatal myocardial infarction. Eur Respir J. 1991;4:1080–1087. [PubMed] [Google Scholar]
  8. Engström G, Olle M, Hedblad B. Population-based study of lung function and incidence of heart failure hospitalizations. Thorax. 2010;65:633–638. doi: 10.1136/thx.2010.135392. [DOI] [PubMed] [Google Scholar]
  9. Wu Y, Vollmer WM, Buist AS, Tsai R, Cen R, Wu X, Chen P, Li Y, Guo C, Mai J, Davis CE. Relationship between lung function and blood pressure in Chinese men and women of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group. Int J Epidemiol. 1998;27:49–56. doi: 10.1093/ije/27.1.49. [DOI] [PubMed] [Google Scholar]
  10. Truelsen T, Prescott E, Lange P, Schnohr P, Boysen G. Lung function and risk of fatal and non-fatal stroke. The Copenhagen City Heart Study. Int J Epidemiol. 2001;30:145–151. doi: 10.1093/ije/30.1.145. [DOI] [PubMed] [Google Scholar]
  11. Engstrom G, Wollmer P, Valind S, Hedblad B, Janzon L. Blood pressure increase between 55 and 68 years of age is inversely related to lung function: longitudinal results from the cohort study ‘Men born in 1914’. J Hypertens. 2001;19:1203–1208. doi: 10.1097/00004872-200107000-00004. [DOI] [PubMed] [Google Scholar]
  12. Sparrow D, Weiss ST, Vokonas PS, Cupples LA, Ekerdt DJ, Colton T. Forced vital capacity and the risk of hypertension. The Normative Aging Study. Am J Epidemiol. 1988;127:734–741. doi: 10.1093/oxfordjournals.aje.a114854. [DOI] [PubMed] [Google Scholar]
  13. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Jr, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105–1116. doi: 10.1016/0895-4356(88)90080-7. [DOI] [PubMed] [Google Scholar]
  14. Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995;152:1107–1136. doi: 10.1164/ajrccm.152.3.7663792. [DOI] [PubMed] [Google Scholar]
  15. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005;26:319–338. doi: 10.1183/09031936.05.00034805. [DOI] [PubMed] [Google Scholar]
  16. Standardization of spirometry--1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987;136:1285–1298. doi: 10.1164/ajrccm/136.5.1285. [DOI] [PubMed] [Google Scholar]
  17. ATS statement--Snowbird workshop on standardization of spirometry. Am Rev Respir Dis. 1979;119:831–838. doi: 10.1164/arrd.1979.119.5.831. [DOI] [PubMed] [Google Scholar]
  18. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr, Jones DW, Materson BJ, Oparil S, Wright JT, Jr, Roccella EJ the National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–1252. doi: 10.1161/01.HYP.0000107251.49515.c2. [DOI] [PubMed] [Google Scholar]
  19. Sidney S, Jacobs DR, Jr, Haskell WL, Armstrong MA, Dimicco A, Oberman A, Savage PJ, Slattery ML, Sternfeld B, Van Horn L. Comparison of two methods of assessing physical activity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Epidemiol. 1991;133:1231–1245. doi: 10.1093/oxfordjournals.aje.a115835. [DOI] [PubMed] [Google Scholar]
  20. Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Resp J. 1999;13:197–205. doi: 10.1034/j.1399-3003.1999.13a36.x. [DOI] [PubMed] [Google Scholar]
  21. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:2645–2653. doi: 10.1056/NEJMoa032158. [DOI] [PubMed] [Google Scholar]
  22. Stanescu D. Small airways obstruction syndrome. Chest. 1999;116:231–233. doi: 10.1378/chest.116.1.231. [DOI] [PubMed] [Google Scholar]
  23. Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airway obstruction in chronic obstructive lung disease. N Engl J Med. 1968;278:1355–1360. doi: 10.1056/NEJM196806202782501. [DOI] [PubMed] [Google Scholar]
  24. Taylor BJ, Johnson BD. The pulmonary circulation and exercise responses in the elderly. Semin Respir Crit Care Med. 2010;31:528–538. doi: 10.1055/s-0030-1265894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peralta CA, Adeney KL, Shlipak MG, Jacobs D, Jr, Duprez D, Bluemke D, Polak J, Psaty B, Kestenbaum BR. Structural and functional vascular alterations and incident hypertension in normotensive adults: the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol. 2010;171:63–71. doi: 10.1093/aje/kwp319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thyagarajan B, Jacobs DR, Jr, Apostol GG, Smith LJ, Jensen RL, Crapo RO, Barr RG, Lewis CE, Williams OD. Longitudinal association of body mass index with lung function: the CARDIA study. Respir Res. 2008;9:31. doi: 10.1186/1465-9921-9-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Engström G, Hedblad B, Nilsson P, Wollmer P, Berglund G, Janzon L. Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study. J Intern Med. 2003;253:5574–5581. doi: 10.1046/j.1365-2796.2003.01138.x. [DOI] [PubMed] [Google Scholar]
  28. Kalhan R, Tran BT, Colangelo LA, Rosenberg SR, Liu K, Thyagarajan B, Jacobs DR, Jr, Smith LJ. Systemic inflammation in young adults is associated with abnormal lung function in middle age. PLoS One. 2010;5:e11431. doi: 10.1371/journal.pone.0011431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thyagarajan B, Smith LJ, Barr RG, Gross MD, Sood A, Kalhan R, Jacobs DR., Jr Association of circulating adhesion molecules with lung function. The CARDIA study. Chest. 2009;135:1481–1487. doi: 10.1378/chest.08-1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thyagarajan B, Jacobs DR, Apostol GG, Smith LJ, Lewis CE, Williams OD. Plasma fibrinogen and lung function: the CARDIA Study. Int J Epidemiol. 2006;35:1001–1008. doi: 10.1093/ije/dyl049. [DOI] [PubMed] [Google Scholar]
  31. Engström G, Lind P, Hedblad B, Wollmer P, Stavenow L, Janzon L, Lindgärde F. Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins. Circulation. 2002;106:2555–2560. doi: 10.1161/01.cir.0000037220.00065.0d. [DOI] [PubMed] [Google Scholar]
  32. Duprez DA, Somasundaram PE, Sigurdsson G, Hoke L, Florea N, Cohn JN. Relationship between C-reactive protein and arterial stiffness in an asymptomatic population. J Hum Hypertens. 2005;19:515–519. doi: 10.1038/sj.jhh.1001860. [DOI] [PubMed] [Google Scholar]
  33. Murphy DM, O’Byrne PM. Recent advances in the pathophysiology of asthma. Chest. 2010;137:1417–1426. doi: 10.1378/chest.09-1895. [DOI] [PubMed] [Google Scholar]
  34. Barr RG, Mesia-Vela S, Austin JH, Basner RC, Keller BM, Reeves AP, Shimbo D, Stevenson L. Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study. Am J Respir Crit Care Med. 2007;176:1200–1207. doi: 10.1164/rccm.200707-980OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mills NL, Miller JJ, Anand A, Robinson SD, Frazer GA, Anderson D, Breen L, Wilkinson IB, McEniery CM, Donaldson K, Newby DE, Macnee W. Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk. Thorax. 2008;63:306–311. doi: 10.1136/thx.2007.083493. [DOI] [PubMed] [Google Scholar]
  36. McAllister DA, Maclay JD, Mills NL, Mair G, Miller J, Anderson D, Newby DE, Murchison JT, Macnee W. Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176:1208–1214. doi: 10.1164/rccm.200707-1080OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Giannotti G, Doerries C, Mocharla PS, Mueller MF, Bahlmann FH, Horvàth T, Jiang H, Sorrentino SA, Steenken N, Manes C, Marzilli M, Rudolph KL, Lüscher TF, Drexler H, Landmesser U. Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. Hypertension. 2010;55:1389–1397. doi: 10.1161/HYPERTENSIONAHA.109.141614. [DOI] [PubMed] [Google Scholar]
  38. Engström G, Gerhardsson de Verdier M, Dahlbäck M, Janson C, Lind L. BP variability and cardiovascular autonomic function in relation to forced expiratory volume: a population-based study. Chest. 2009;136:177–183. doi: 10.1378/chest.08-2529. [DOI] [PubMed] [Google Scholar]

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