Our results show that, compared to adults who have a normal pulmonary function, adults who have impaired lung function, whether restrictive or obstructive in nature, have a number of abnormalities in their cardiovascular risk profile that might help to explain their increased risk for cardiovascular mortality. However, the comparisons of cardiovascular risk profiles with persons who had normal pulmonary function differed somewhat between adults with a restrictive impairment and those with an obstructive impairment. Persons with restrictive impairment showed more abnormalities of cardiometabolic factors compared to the normal group whereas the latter had primarily higher rates of smoking along with evidence of systemic inflammation compared to the normal group. Furthermore, the predicted 10-year cardiovascular risk was increased among adults aged 50–74 years with either a restrictive or obstructive impairment.
Relatively few studies, especially population-based studies in the United States, have compared the cardiovascular risk factor profile in people with COPD to that in people without COPD. In a cohort of 91932 members of the Kaiser Permanente Medical Care Program of Northern California, patients with COPD identified from administrative databases were more likely to have diabetes, hypertension, and hyperlipidemia and to be obese than patients without COPD . In the Copenhagen City Heart Study, the GOLD classification system was used to establish the respiratory status of participants . The unadjusted percentages of elevated concentrations of HbA1c and C-reactive protein as well as the mean concentration of total cholesterol, mean systolic blood pressure, mean body mass index, and current smoking were higher in 1036 participants with COPD than in 4854 without COPD. However, many of the differences were likely attributable to the much higher mean age in participants with COPD. An analysis of patients with COPD from the United Kingdom identified from the General Practice Research Database reported that patients with COPD were more likely to be underweight, less likely to be obese, and less likely to have hypertension than patients without COPD . In another study that used spirometric testing to establish the COPD status, hypertensive patients with COPD (N=1622) were more likely to smoke and have a higher mean systolic blood pressure than hypertensive patients without COPD (N=1184), but the prevalence of diabetes in the two groups did not differ significantly . In a Korean study of 4001 participants aged ≥18 years, those with obstructive lung function had a higher unadjusted mean waist circumference, systolic blood pressure, diastolic blood pressure, and higher concentrations of glucose and triglycerides but lower concentration of high-density lipoprotein cholesterol . Thus, the available data do not paint a consistent picture about risk factors for cardiovascular disease among people with COPD. Some of the inconsistency may be attributable to differences in methods used to identify participants with COPD (identification from administrative data bases, use of pulmonary function test to categorize COPD status), sample size of the studies, definition of risk factors (self-reported data, administrative data bases, measured data), or other characteristics of study populations. Our results confirm that advanced age and a high prevalence of smoking are the two factors that contribute substantially to the risk for cardiovascular disease among U.S. adults with COPD.
Little information about predicted cardiovascular risk in function of pulmonary function status is available. In an Italian study of 12933 participants aged ≥35 years, the CUORE risk score was not significantly associated with the ratio of FEV1/FVC .
People with an obstructive impairment continued to smoke at high rates. Consequently, smoking cessation efforts are critical to reducing the risk for cardiovascular disease among these people. A large body of research has examined the effectiveness of numerous approaches to smoking cessation such as clinical interventions (including behavioral approaches and medications), system interventions, and quitlines . Despite this large body of research concerning the best approaches to initiate and sustain smoking cessation, the report “Treating Tobacco Use and Dependence: 2008 Update” acknowledged the need for additional research concerning the effectiveness of counseling among people with COPD. In view of the strong link between smoking and COPD and the high rates of smoking among people with COPD, such research is urgently needed. A meta-analysis of randomized controlled trials found that the combination of smoking cessation counseling plus the use of nicotine replacement therapy yielded the best rate of smoking cessation, followed by the combination of smoking cessation counseling plus the use of antidepressant medications, and smoking cessation counseling alone . Among patients with COPD, both intensive counseling and pharmacotherapy yielded superior cost-effectiveness compared to minimal counseling .
Previous studies have shown that COPD is associated with increased concentrations of C-reactive protein [26–28]. Our analysis found that concentrations of C-reactive protein were elevated in adults with moderate or severe COPD but not in those with a mild obstructive impairment. Because C-reactive protein is considered to be a risk factor for cardiovascular disease , the presence of a systemic inflammatory component as evidenced by elevated concentrations of C-reactive protein in people with COPD may help to explain the increased risk for cardiovascular disease in this population.
In addition to excess levels of smoking and elevated concentrations of C-reactive protein, several additional physiological disruptions may contribute to the increased risk for cardiovascular disease in people with COPD including increased circulating platelet-monocyte aggregates , impaired coronary blood flow , endothelial dysfunction [32, 33], coagulation abnormalities , oxidative stress , and increased arterial stiffness .
The impact of medications used to treat COPD provides another possible explanation for the increased risk for cardiovascular disease . Evidence has been presented that the use of short-acting anticholinergic agents may increase mortality from cardiovascular disease . The data concerning the effect of long-acting anticholinergic agents on adverse cardiovascular events has generated intense discussion [38–43]. Furthermore, a meta-analysis of randomized controlled trials concluded that the use of beta-2-agonists increased cardiovascular events . Studies concerning the possible effect of inhaled corticosteroids on cardiovascular outcomes have yielded conflicting data with observational studies showing a possible benefit from the use of these agents and data from randomized controlled trials showing no such effect . Because patients with COPD are susceptible to acute exacerbations of their disease in part from respiratory infections, some classes of antibiotics used to treat these infections such as macrolides and quinolones could conceivably result in adverse cardiovascular events .
Our results suggest that people with a mild obstructive impairment do not have a particularly adverse set of cardiometabolic risk factors compared to people with normal respiratory function. Thus, the clinical approach to cardiovascular risk reduction in this population should be similar as that for the general population [47–52]. Although research concerning management of cardiovascular risk factors specifically in patients with COPD is limited, some data suggest that the use of beta-blockers in patients may reduce cardiovascular morbidity and mortality. In a study of 1205 patients with COPD undergoing vascular surgery, beta-blocker therapy, particularly high-dose therapy, was associated with reduced mortality . In addition, the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have also been shown to reduce cardiovascular events in cohorts of patients with COPD . Interestingly, some treatments for COPD may provide cardiovascular benefits to patients with COPD. For example, pulmonary rehabilitation in patients with COPD was associated with improvements in aortic pulse wave velocity, blood pressure, and concentration of total cholesterol .
Our analyses of the prebronchodilator data indicated that the prevalence of hypercholesterolemia was somewhat lower among participants with at least moderate obstructive impairment. The explanation for this finding is unclear, and it could represent a spurious finding. The age-adjusted self-reported use of cholesterol-lowering medications and mean intakes of saturated fat and polyunsaturated fat were similar for participants with normal lung function and those with at least moderate obstructive impairment (data not shown). Results from other studies yield mixed evidence about a reduced prevalence of hypercholesterolemia among adults with COPD. In a large study from Canada, 7.9% of patients with COPD and 10.9% of patients without COPD had hypercholesterolemia, a difference which was significantly different . Mean concentrations of low-density lipoprotein cholesterol were also lower in a population of patients with COPD evaluated for lung transplantation . In contrast in a Danish study, unadjusted mean concentrations of total cholesterol were positively associated with severity of COPD . In an Italian study, unadjusted mean concentrations of total cholesterol and low-density lipoprotein cholesterol did not differ between participants with and without COPD . Also, unadjusted mean concentrations of total cholesterol and low-density lipoprotein cholesterol did not differ significantly between patients with emphysema and those without this condition in another study .
In recent years, the potential role of treatment with statins in reducing morbidity and mortality among people with COPD has drawn substantial interest [58–60]. The use of statins to manage hypercholesterolemia should yield similar benefits in people with COPD as in those without this condition. Because statins have been shown to have pleiotropic actions including anti-inflammatory and antioxidant effects  and because COPD has a powerful inflammatory component , statins could conceivably modulate the inflammation unleashed by COPD. Whether statins will reduce cardiovascular morbidity and mortality in people with COPD to the same extent as in people without COPD or whether there is an added benefit to the use of statins in people with COPD remains a question to be addressed by future randomized controlled trials. Of note is that a recent study showed that the use of statins was associated with interstitial lung disease among smokers .
A heterogeneous set of disorders can produce a restrictive pattern on spirometry . These disorders can be broadly grouped into three categories: decreased lung compliance (interstitial lung disease, pneumonia, sarcoidosis, acute respiratory distress syndrome), decreased muscle strength (neuromuscular disease, dysfunction of diaphragm, injury of the phrenic nerve), and extrapulmonary disease (pleural effusion, pleural thickening, obesity, metabolic syndrome, kyphoscoliosis). In turn, some of these conditions such as interstitial lung disease have a lengthy list of etiologies.
Observational studies have shown that people with a restrictive impairment have an increased mortality rate from all-causes as well as diseases of the circulatory system . Yet, the cardiovascular risk profile of people with restrictive impairment has not been well characterized. In an analysis of 4320 U.S. adults aged 25–74, participants with a restrictive impairment were more likely to be current smokers, be obese, have hypertension, and have diabetes than participants without restriction . A study of 121,965 French participants showed that a restrictive ventilator pattern was associated with several factors (lipids, glucose-blood pressure, and abdominal obesity) derived from a factor analysis of cardiometabolic variables . Furthermore, adults with a restrictive impairment also show evidence of inflammation . In our analysis, the presence of a number of cardiometabolic abnormalities (increased body mass index, low high-density lipoprotein cholesterol, increased diabetes, elevated C-reactive protein) among the adults with a restrictive impairment is broadly consistent with the aforementioned studies and suggests that these adults are at increased risk for cardiovascular disease. Although our analyses did not specifically examine the association between metabolic syndrome and restrictive ventilatory pattern, the significant associations between several of the cardiovascular risk factors and restrictive impairment is consistent with previous studies that have reported associations between metabolic syndrome and restrictive impairment [21, 66–69]. The general profile of these adults suggests that, as a group, they might benefit from weight management, improved nutrition, and increased physical activity in addition to smoking cessation. Furthermore, pharmacotherapy to address hyperglycemia or raise concentrations of high-density lipoprotein cholesterol may help to lessen the cardiovascular risk in these adults.
The major strength of this study is the large nationally representative study population of U.S. adults with spirometry and cardiovascular measurements. The principal limitation of our study was the very small number of adults with a very severe obstructive impairment. Therefore, we were unable to generate results for this specific group. Even the number of adults with severe obstructive impairment proved to be limited leading us to group moderate, severe, and very severe obstructive impairment together.
Although the results based on postbronchodilator data in large measure were similar to the results based on prebronchodilator data, these postbronchodilator results should be cautiously interpreted given the substantial attrition of attendance with 25% of participants aged 20–79 years excluded for safety reasons and another 21% of participants not having the postbronchodilator examination. The safety exclusions included a number of reasons that excluded a number of participants at increased risk for cardiovascular disease: uncontrolled blood pressure, irregular pulse on examination, taking medication for major arrhythmia, implanted defibrillator, and current treatment for cardiac disease.
Addressing the cardiovascular risk factors among persons with restrictive or obstructive pulmonary function would provide support to the federal interagency Million Hearts Initiative to prevent 1 million heart attacks and strokes over the next 5 years [70, 71]. The proposed effective clinical services that could reduce cardiovascular disease risk, morbidity, and mortality in this patient population include aspirin therapy, blood pressure control, cholesterol management, and smoking cessation . This initiative has been expanded to include community-level policies and programs designed to reduce exposure to tobacco use, policies to reduce sodium content of food, and policies to eliminate artificial trans fatty acids from the diet .