COPD Linked to Increased Mortality, Hospitalization Risk in Patients With HFpEF

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of long-term all-cause mortality and hospitalization among patients with heart failure with preserved ejection fraction (HFpEF), according to a study published in ESC Heart Failure.¹

Affecting more than 64 million people worldwide, HF has been identified as a significant life-threatening syndrome with high morbidity and mortality.² The prevalence of HFpEF has been rising and now occupies almost half of HF cases; HFpEF is defined as the presence of HF signs and symptoms, with left ventricular ejection fraction (LVEF) exceeding 50%.³

COPD is a major HF comorbidity, as one-third of patients with HF have comorbid COPD.¹ Of those with HF, COPD is most prevalent in patients with HFpEF.⁴ More specifically, among the HFpEF population, COPD was prevalent in 16% of those in randomized controlled trials (RCTs) and 14% to 34% of both hospital and outpatient cohorts.⁵

Despite this, most research on whether COPD can serve as an independent prognostic risk factor of HF encompasses the entire HF population.¹ Because of the clinical manifestations and pathological mechanisms among patients with HFpEF vs those with HF with reduced ejection fraction, COPD may impact these 2 groups differently. Consequently, the researchers conducted a systemic review and meta-analysis to detect the adverse effects of comorbid COPD in patients with HFpEF.

Chronic obstructive pulmonary disease significantly heightens the risk of mortality and hospitalization in patients with heart failure with preserved ejection fraction. | Image Credit: catinsyrup - stock.adobe.com

Up to April 2023, the researchers searched 3 electronic databases—EMBASE, PubMed, and Cochrane Library—for potentially eligible studies that reported the adverse effects of COPD on those with HFpEF; to do so, they used terms that included COPD, heart failure, mortality, and hospitalization. Eligible studies included RCTs or observational studies focused on patients with coexisting COPD and HFpEF that analyzed at least one of the clinical-associated adverse outcomes, including both all-cause mortality and hospitalization.

The researchers initially retrieved 1013 studies, 11 of which they included in their final analysis. The 11 studies comprised 8 observational studies and 3 post hoc RCTs; the pooled study population contained 18,602 patients. They recorded various data from each study, including the study design, sample size, and reported outcomes. Of the included studies, 6 only investigated mortality, 1 only investigated hospitalization, and 4 investigated both.

More specifically, 5 reported on the composition of hospitalization or mortality-associated outcomes. Compared with patients with HFpEF without COPD, each study indicated that the coexistence of HFpEF and COPD contributed to patients’ adverse outcomes (risk ratio [RR], 1.59; 95% CI, 1.30-1.93; P < .00001).

Also, 10 studies analyzed all-cause mortality in patients with HFpEF either with or without COPD. Four studies indicated that COPD was not associated with increased mortality of patients with HFpEF. However, the researchers noted that their synthesized data determined that COPD significantly increased the mortality rate of patients with HFpEF (RR, 1.62; 95% CI, 1.34-1.95; P < .00001).

Additionally, they conducted a subgroup analysis of cardiovascular-related mortality and postdischarge all-cause mortality. Only 2 studies analyzed cardiovascular-related mortality, and both found that it increased in patients with HFpEF and COPD (RR, 1.59; 95% CI, 1.30-1.93; P < .00001).

Conversely, 4 studies investigated just postdischarge all-cause mortality. One study reported that patients with HFpEF and COPD did not face increased postdischarge mortality risk, while the other 3 studies found an increased risk among this population. Therefore, the researchers determined that COPD significantly increased the postdischarge mortality risk in patients with HFpEF (RR, 2.57; 95% CI, 1.34-4.93; P < .01).

Lastly, hospitalization-associated outcomes were reported in 4 studies, all of which found that COPD significantly increases the hospitalization rate in patients with HFpEF (RR, 1.66; 95% CI, 1.47-1.87; P < .00001). As for the subgroup analysis, 3 studies investigated HF-caused hospitalization. Each study found that COPD promoted the occurrence of HF-caused hospitalization in patients with HFpEF (RR, 1.64; 95% CI, 1.44-1.87; P < .00001).

The researchers acknowledged their limitations, one being that they only considered studies reported in English for inclusion. Therefore, a potential language bias may exist, and the study population may not be representative of all ethnic groups; this could affect the generalizability of their findings. Despite their limitations, the researchers expressed confidence in their findings, using them to suggest potential next steps.

“…our meta-analysis supported that COPD comorbidity significantly increases the risks of mortality and hospitalization in patients with HFpEF,” the authors concluded. “Developing rapid clinical diagnostic indicators and early use of novel drugs such as SGLT-2 [sodium-glucose co-transporter 2] and ARNI [angiotensin receptor neprilysin inhibitors] may improve the prognosis of this population, deserving further study.”

References

1. Zhou J, Liu Y, Yang F, et al. Risk factors of sarcopenia in COPD patients: a meta-analysis. Int J Chron Obstruct Pulmon Dis. 2024;19:1613-1622. doi:10.2147/COPD.S456451

2. Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023;118(17):3272-3287. doi:10.1093/cvr/cvac013

3. Bozkurt B, Coats AJ, Tsutsui H, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. Published online March 1, 2021. doi:10.1016/j.cardfail.2021.01.022

4. Ather S, Chan W, Bozkurt B, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59(11):998-1005. doi:10.1016/j.jacc.2011.11.040

5. Triposkiadis F, Giamouzis G, Parissis J, et al. Reframing the association and significance of co-morbidities in heart failure. Eur J Heart Fail. 2016;18(7):744-758. doi:10.1002/ejhf.600