Age-associated increases in pulmonary artery systolic pressure in the general population

Abstract

Background: In contrast to the wealth of data on isolated systolic hypertension involving the systemic circulation in the elderly, much less is known about age-related change in pulmonary artery systolic pressure (PASP) and its prognostic impact in the general population. We sought to define the relationship between PASP and age, to evaluate which factors influence PASP, and to determine whether PASP is independently predictive of mortality in the community.

Methods and results: A random sample of the Olmsted County, Minn, general population (n=2042) underwent echocardiography and spirometry and was followed up for a median of 9 years. PASP was measured from the tricuspid regurgitation velocity. Left ventricular diastolic pressure was estimated with Doppler echocardiography (E/e' ratio), and arterial stiffening was assessed from the brachial artery pulse pressure. Among 1413 subjects (69%) with measurable PASP (age, 63+/-11 years; 43% male), median PASP was 26 mm Hg (25th to 75th percentile, 24 to 30 mm Hg) and increased with age (r=0.31, P<0.001). Independent predictors of PASP were age, pulse pressure, and mitral E/e' (all P< or =0.003). Increasing PASP was associated with higher mortality (hazard ratio, 2.73 per 10 mm Hg; P<0.001). In subjects without cardiopulmonary disease (any heart failure, coronary artery disease, hypertension, diabetes mellitus, or chronic obstructive lung disease), the age-adjusted hazard ratio was 2.74 per 10 mm Hg (P=0.016).

Conclusions: We provide the first population-based evidence of age-related increase in pulmonary artery pressure, its association with increasing left heart diastolic pressures and systemic vascular stiffening, and its negative impact on survival. Pulmonary artery pressure may serve as a novel cardiovascular risk factor and potential therapeutic target.

Figure 1. Distribution of pulmonary artery systolic pressure in the general community

The cumulative frequency distribution of pulmonary artery systolic pressure (PASP) in the population is shown. Median (25^th, 75^th percentile) PASP was 26 (24, 30) mmHg.

Figure 2. Association of systemic and pulmonary arterial systolic pressures with age

In the systemic circulation (A), brachial artery systolic blood pressure (SBP) increased with age. In the pulmonary circulation (B), pulmonary artery systolic pressure (PASP) similarly increased with age in men (gray) and women (black) in the population. For each association, raw data points, linear regression line, Pearson's correlation coefficient, and probability value for the association are shown. Across age quartiles (C), the % increase in SBP (gray) and PASP (black) relative to the youngest quartile was strikingly similar in the systemic and pulmonary circulations.

Figure 3. Association of pulmonary artery systolic pressure with systemic arterial stiffening and left ventricular diastolic dysfunction

Pulmonary artery systolic pressure (PASP, shown in log scale) increased in association with evidence of systemic vascular stiffening (increasing pulse pressure, shown in A) and increasing diastolic pressures (increasing mitral E/e' ratio shown in B). For each association, raw data points, linear regression line, Pearson's correlation coefficient, and probability value for the association are shown.

Figure 4. Kaplan-Meier curves showing the association of increasing pulmonary artery systolic pressure with decreasing survival in the community

In the entire population (A), increasing quintiles of pulmonary artery systolic pressure (PASP) was associated with reduced survival by Kaplan-Meier analysis (overall Log Rank p<0.001). *Bonferroni-adjusted p<0.05 in pairwise comparison to the lowest quintile. In the subset of the population without cardiopulmonary disease (B), increasing tertiles of PASP was similarly associated with reduced survival (overall Log Rank p=0.002). *Bonferroni-adjusted p<0.05 in pairwise comparison to the lowest tertile.

Figure 4. Kaplan-Meier curves showing the association of increasing pulmonary artery systolic pressure with decreasing survival in the community

In the entire population (A), increasing quintiles of pulmonary artery systolic pressure (PASP) was associated with reduced survival by Kaplan-Meier analysis (overall Log Rank p<0.001). *Bonferroni-adjusted p<0.05 in pairwise comparison to the lowest quintile. In the subset of the population without cardiopulmonary disease (B), increasing tertiles of PASP was similarly associated with reduced survival (overall Log Rank p=0.002). *Bonferroni-adjusted p<0.05 in pairwise comparison to the lowest tertile.