CVD Mortality in COPD Related to Factors Other than Lung Function Decline

In COPD patients, a new study found no association between lung function decline and individual CVD outcomes, but disease exacerbations and dyspnea were implicated.

Frequent and severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and increased breathlessness are associated with risk of cardiovascular disease (CVD) outcomes and mortality in patients with COPD, according to results of a new study from the United Kingdom.

In contrast, the rate of forced expiratory volume in 1 second (FEV1) decline had no association with composite CVD outcomes.

Accelerated decline in lung function has been associated with risk of CVD in a general population. There is much less known, however, about the association in COPD.

The study authors, led by Hannah Whittaker of the National Heart and Lung Institute at Imperial College, London, note that theirs is the first large observational study to assess the association between accelerated lung function decline and CVD outcomes and mortality for patients with COPD. Findings appear online ahead of print in the European Respiratory Journal.


COPD patients without a history of CVD were drawn from the Clinical Practice Research Datalink (CPRD-GOLD) primary care dataset of more than 36 000 patients.

The fastest quartile of the COPD population’s decline was used to define accelerated FEV1decline. Cox regression assessed the association between baseline accelerated FEV1decline and a composite CVD outcome (at right)

Composite CVD outcome

Myocardial infarction, ischemic stroke,
heart failure, atrial fibrillation.coronary artery disease,
CVD mortality

Model adjusted for

Age, gender, smoking status, BMI,
history of asthma, hypertension, diabetes,
statin use, dyspnea,
exacerbation frequency,
baseline FEV1 percent predicted


During a mean follow-up of 3.6 years, 6110 (16.8%) patients experienced a CVD event. Over that time, the median rate of FEV1 decline was -19.4 ml/year (IQR, -40.5 to 1.9). One in 4 patients included in the study experienced accelerated FEV1 decline (>-40.5 ml/year).

The researchers observed that accelerated FEV1 decline did not appear to impact the risk of composite CVD events in either the unadjusted analysis (HRunadj = 0.99; 95% CI, 0.93–1.05) or the fully adjusted analysis (HRadj=0.98; 95% CI, 0.90–1.06).

There was also no association seen between FEV1 decline and individual CVD outcomes (adjusted hzard ratio):

  • Heart failure (0.99; 95% CI, 0.83-1.20)
  • Myocardial infarction (0.89; 95% CI, 0.70-1.12)
  • Stroke (1.01; 95% CI: 0.82- 1.23);
  • Atrial fibrillation (0.97; 95% CI, 0.81-1.15);
  • Coronary artery disease (1.02; 95% CI, 0.87-1.19)
  • CVD mortality (0.94; 95% CI, 0.71-1.25).

However, both increased frequency/severity of AECOPD and increased dyspnea were associated with all CVD outcomes individually in unadjusted models.

Other factors associated with increased risk for CVD events including increasing age, male gender, current smoking status, hypertension, and current statin use.

The authors note their findings suggest “…that other markers of disease severity, rather than rate of lung function decline, might be more closely related to CVD outcomes and mortality. This observation is in keeping with previous observational studies which have demonstrated that the period immediately following an AECOPD are extremely high risk for CVD events such as myocardial infraction and stroke relative to periods of more stable disease.

Limitations to the study noted by the authors include immortal time bias in the study design; the possibility that asthma may have been misdiagnosed as COPD in some patients; and that not all patient characteristics are recorded within the health record, leading to residual confounding.

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