Dr Antonio Anzueto on the Ties Between COPD, Cardiovascular Disease

Antonio Anzueto, MD, recently spoke with The American Journal of Managed Care® (AJMC®) about the latest advances in therapy for chronic obstructive pulmonary disease (COPD), as well as what is known about the relationship between COPD and cardiovascular disease. Anzueto is a professor of medicine and section chief of pulmonary at South Texas Veterans Healthcare System, an affiliated institution with the University of Texas Health San Antonio, Texas.

This interview has been edited for clarity.

AJMC®: What is the link between COPD and cardiovascular conditions? Are individuals with COPD more likely to have concurrent cardiovascular disease, or are they more susceptible to developing cardiovascular conditions?

Anzueto: This is the recognition that the individual with COPD has more than COPD. This was proposed originally by the GOLD initiative around 2014—we added a section of multiple comorbid conditions associated with COPD. Since that time, the whole concept has evolved, because now we recognize that the precipitating factors for both COPD and cardiovascular disease are pretty much similar due to cigarette smoking. So, it makes sense to think about patients with COPD are likely to have cardiovascular disease. Digging deeper, now we can understand that that cardiovascular conditions are the most common comorbid conditions that are associated with COPD or concomitant condition associated with COPD and vice versa. A patient with cardiovascular disease has significant chronic obstructive pulmonary disease. Up to half of the patients with a diagnosis of COPD carry the diagnosis of a cardiovascular condition.

This association is huge. And this association implies a 2-way street. My job [is], if my patient has cardiac comorbidities, [and] he or she is receiving appropriate therapy for the cardiac comorbidities, that can potentially be accentuated and make the situation worse, especially if the patient has an exacerbation.

The other side, from the cardiology side, if the patient doesn't have a diagnosis of COPD, I think it is crucial that these patients get a spirometry and identify if they do have COPD and cardiovascular disease and to receive appropriate therapy. To answer your question, the association is huge—a large number of patients with COPD do have cardiovascular conditions.

AJMC®: From a pathophysiological perspective, is there any overlap between COPD and cardiovascular disease?

Anzueto: There is this concept of systemic inflammation, and that systemic inflammation affects the lungs and also affects the cardiovascular and the endovascular systems and produces the formation of plaques that eventually induce a cardiac event. On the other hand, the patient with COPD, one of the major landmarks of their clinical feature is the presence of hyperinflation. They are not able to fully empty their lungs on each breath. Air accumulates inside the lungs, and as a consequence, what we've seen is that the hyperinflation affects the cardiovascular side, decreases the function of the heart, both the left and the right ventricle.

AJMC®: COPD and cardiovascular disease both place a great deal of burden on the health care system from a clinical and economic perspective. Could you please describe the clinical and economic impact of these burdens on patients with COPD and cardiovascular disease as well as on the health care system?

Anzueto: The patients who have COPD and cardiovascular conditions, if they happen to have a COPD exacerbation, it's more likely going to require hospitalization, and hospitalizations are the major driver of costs. And morbidity and mortality in patient with COPD. So, the patient will need to be hospitalized. These patients may either have an exacerbation where they will be required to be re-hospitalized; they may have a cardiovascular event following these hospitalizations.

AJMC®: To follow up, how does the development of cardiovascular diseases with COPD impact mortality for patients?

Anzueto: There have been several observations that a patient who has an exacerbation and they're hospitalized with an exacerbation, they have a significantly increased rate in the next 30 days to have an acute cardiovascular event and even have a cerebrovascular accident like a stroke. We know when we start seeing these data, we can scratch our chin and say, "Wow, wait a minute. What does this have to be?" This person was hospitalized because of a worsening of his or her lung condition, had a COPD exacerbation, probably had an acute bronchitis that made him or her significantly compromised or required hospitalization, and is at an increased risk of a cardiac event.

So, that's when we start going deeper and try to understand this relationship. And now we can clearly see we have very large epidemiological data that clearly correlate that the acuity of cardiopulmonary events trigger increased cardiovascular events.

And furthermore, now we have clinical trials that can show with medication, with inhaled medications, that they can decrease exacerbations. What these studies are showing at the end of the day, they're not only decreasing exacerbations, they are decreasing mortality, primarily a decrease of cardiovascular mortality. We have gone all the way to close the circle that a patient with COPD has cardiovascular comorbidities; if they have an exacerbation they are more likely to have a cardiovascular event, and to have cardiovascular mortality due to cardiovascular events. And if we can prevent those exacerbations, we may even prevent some of these cardiovascular events.

AJMC®: Proper diagnosis and treatment are paramount to the management of individuals with COPD and cardiovascular disease. How can we best promote prompt and accurate diagnosis for individuals and what are available treatment options to better manage COPD and reduce the risk of developing cardiovascular diseases or other adverse events?

Anzueto: One part of that question is proper diagnosis, spirometry. Spirometry is the way to diagnose COPD. So [for example if] the patient happened to be a smoker, [or] wasn't a smoker in the past, [or with] any respiratory symptoms—we have to do a spirometry to understand what they have. The patient who has a cardiovascular disease has already been identified. Any kind of a cardiac event, the person needs to have a spirometry to identify they have COPD. So, it goes back to spirometry, and the cardiovascular disease.

I have patients that I treat, I know they have COPD, they are stable but keep telling me, "I'm short of breath, I'm limited." They have signs of heart failure, but it's important for these patient to get an echocardiogram. Those patients, I will allow my cardiologist to see them; they will do risk stratification; they will stress test them. And some of them end up needing to have a cardiac cath right or left side. And it's not unusual for some of those patients who have COPD, they come back from the cardiologist with stents inside their heart, or they come with a scar in the chest, so they have to have some surgery because there's significant cardiovascular disease. Now, in the other hand, how can we prevent the events? We know that cardiac events in general can be prevented by cardio protection medications from treating the cholesterol to treating the diabetes. Beta blockers, another class of medications after having an acute event have been shown to significantly reduce the risk of future events. We have done clinical trials in patients with COPD given beta blockers, and they did not show any significant improvement in outcomes. And it was in part because when those trials were done, we didn't have the optimal therapy for COPD. Now we know that patients who receive triple therapy and the more recent clinical trials for the triple therapy formulations that are available have much pretty [highlighted] more information about this. First because these were huge studies, including the 3 studies with over 30,000 patients, and we clearly saw that exacerbations can be prevented. And also, patients treated with triple therapy have significant decreases in the relative risk of mortality versus the other interventions. So, we demonstrated that exacerbations can be prevented, and this can result in reduction in mortality due to cardiovascular events.

AJMC®: Are there particular age groups that we should focus on when attempting to identify and treat comorbid cardiovascular disease in the COPD population? And who benefits most from early intervention?

Anzueto: The face of COPD have changed. I tell my team, don't look for a 79-year-old male that he has COPD, because he either has already been diagnosed or he's dead of his cardiovascular condition. I think the challenge today is diagnose COPD in a woman who is in her early 50s. And I remember a couple of years ago was this initiative about the red dress for women to recognize that women have significant cardiovascular events. And this is the same situation that we have for COPD—women in their early 50s. They had COPD. And unfortunately, they don't get diagnosed. They get diagnosed with sinus, allergies, asthma, all of the above. Their symptoms persist and it doesn’t occur to us, "I should probably do spirometry and see if this lady has COPD." And sure enough, you will identify the COPD. This early identification of the disease is crucial.

One, because we have pharmacotherapy today for COPD that we slow the progression of the disease—no question about it. Long-acting bronchodilators have changed COPD to make it a treatable disease. The sooner we start treating those patients, the better they're going to be in the long term. And second, it will allow us to understand other comorbid conditions. Yes, my patient has COPD, she happened to smoke in her 40s, she's not smoking anymore. But can she have cardiovascular risks? So, we need to look for and evaluate for cardiovascular conditions. The name of the game is the sooner the better. The face has changed—it's women we need to look for, and the age is under the age of 55, 60. For sure.