The basis for the high prevalence of elevated PAWP in our
series, as well as others (22,23) is likely multifactorial. It is
well recognized that cardiovascular disease (CVD) is highly
prevalent in COPD and accounts for a substantial proportion
of morbidity and mortality (26). We found a weak relationship between PAWP and systemic HTN, but not CAD.
Subclinical systemic vascular disease in the form of
atherosclerosis (27) with consequent endothelial dysfunction and arterial stuffiness (28) may lead to LV diastolic
dysfunction. The strong influence of BMI on PAWP noted
here is consistent with the recognized increased risk of non-systolic heart failure with obesity (29). Mean pulmonary
arterial pressures and PAWP typically rise with exercise
in advanced COPD. This rise has been shown to occur
with hyperventilation alone (30), indicating a contribution
from air trapping and consequent hyperinflation. We found
no association between pulmonary function measures of
hyperinflation and resting mPAP or PAWP. In the series
of Scharf et al., mPAP was not related to lung volumes or
emphysema scores by computed tomography (22).
Statins have numerous beneficial effects in CVD that
could account for the lower PAWP observed in this study.
Their use is associated with small reductions in blood pressure (31–33) as well as reduced left ventricular hypertrophy and fibrosis both in experimental animal models and
in humans (34–36). Statins increase arterial distensibility
(32, 37) and induce regression of aortic atherosclerosis (38),
likely through beneficial effects on endothelial function
(39–43). At a cellular level, normal myocardial relaxation
requires calcium scavenging through a process dependent
upon sarcoplasmic reticulum Ca2+ ATPase (SERCA) activity,
the impairment of which has been associated with diastolic
dysfunction (44). Endothelin may also promote diastolic dysfunction by a mechanism involving induction of intracellular
alkalosis which in turn affects myofilament Ca2+ sensitivity.
Statins could improve diastolic function through their beneficial effects on SERCA (45) as well as reduced endothelin
activity in the heart (46).
Despite the high prevalence of elevated PAWP in PH
associated with COPD, the primary pathophysiologic mechanism is felt to be structural remodeling of the small pulmonary arteries, which occurs early in the disease (47).
Recent data from the NETT trial found a strong correlation
between mPAP and the cross-sectional area of the small pulmonary vessels by computed tomography (48). Statins possess numerous properties that would be expected to retard
pulmonary vascular remodeling, including inhibition of vascular smooth muscle cell (VSMC) proliferation and migration, induction of VSMC apoptosis, and have been shown to
be effective in several animal models of PH (15,16,49,50).
Despite no effect on PVR, our observation of reduced
mPAP independently of PAWP in statin users suggests that
these drugs may reduce pulmonary vascular remodeling in
The association between age and mPAP, but not PAWP,
was unexpected. Advanced age is well known to correlate
with left ventricular diastolic dysfunction (51,52), and so a
correlation with PAWP would have been predicted. Longitu-
dinal studies have shown a mPAP rise of 0.4 to 0.6 mmHg
per year in patients with COPD ( 53, 54), which is in line
with our β coefficient estimate. Thus, increased age with
consequent longer disease duration, may be associated with
more pulmonary vascular remodeling. Cross sectional stud-
ies, however, are significantly affected by survival bias and
rarely demonstrate this correlation. A large series presented
by Bishop et al., including 595 subjects with COPD, found no
correlation between mPAP and age ( 55).
In patients with severe COPD, statin use is associated with
significantly lower mPAP and PAWP despite older age and a
higher prevalence of medical comorbidities such as HTN and
coronary disease. Improvements in pulmonary hemodynamics may represent an addition to the growing list of potential
benefits of statin use in COPD ( 56). Prospective clinical trials
are required to assess the long-term clinical impact of statin
therapy in this population.
Disclosures: None of the authors have any conflicts of interest to disclose. The authors alone are responsible for the
content and writing of the paper.
1. Oswald-Mammosser M, Weitzenblum E, Quoix E, Moser
G, Chaouat A, Charpentier C, et al. Prognostic factors in
COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest 1995; 107(5):1193–
2. Weitzenblum E, Hirth C, Ducolone A, Mirhom R, Rasaholin-janahary J, Ehrhart M. Prognostic value of pulmonary artery
pressure in chronic obstructive pulmonary disease. Thorax 1981;
3. Kessler R, Faller M, Fourgaut G, Mennecier B, Weitzenblum E.
Predictive factors of hospitalization for acute exacerbation in a
series of 64 patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med 1999; 159(1):158–164.
4. Sims MW, Margolis DJ, Localio AR, Panettieri RA, Kawut SM,
Christie JD. Impact of pulmonary artery pressure on exercise
function in severe COPD. Chest 2009; 136(2):412–419.