Repeat Tests for Inflammation Aid Prognosis After Acute Heart Failure

Longitudinal high-sensitivity C-reactive protein (hsCRP) testing helped identify people with the worst outcomes following hospitalization for acute heart failure, researchers found from a Chinese cohort study.

Long-term cumulative systemic inflammation — estimated using repeated hsCRP measurements at admission and 1 and 12 months after discharge — correlated with all-cause mortality rates over nearly 5 years, independent of conventional risk factors:

• Quartile 1 cumulative hsCRP: 19.0% (reference)
• Quartile 2 cumulative hsCRP: 25.0% (HR 1.29, 95% CI 0.92-1.81)
• Quartile 3 cumulative hsCRP: 29.1% (HR 1.62, 95% CI 1.16-2.25)
• Quartile 4 cumulative hsCRP: 43.8% (HR 2.38, 95% CI 1.75-3.23)
• Excess hsCRP at 0 out of the 3 time points: 16.2% (reference)
• Excess hsCRP at 1 out of the 3 time points: 22.8% (HR 1.36, 95% CI 0.92-2.01)
• Excess hsCRP at 2 out of the 3 time points: 29.9% (HR 1.95, 95% CI 1.34-2.82)
• Excess hsCRP at 3 out of the 3 time points: 42.2% (HR 2.80, 95% CI 1.97-4.00)

“Our findings suggest that repeated hsCRP assays could assist physicians in identifying patients with a high risk of death,” reported Lihua Zhang, MD, PhD, of Fuwai Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College in Beijing, and colleagues in the Journal of the American Heart Association.

A known inflammatory biomarker, hsCRP assessed at a single time point has previously been associated with worse outcomes among heart failure patients.

“However, rather than being a static level that remains unchanged after a single assessment, the hsCRP level is a dynamic risk factor fluctuating over time,” Zhang’s group asserted in reporting that elevated long-term cumulative hsCRP level may also be of prognostic value.

For a cohort that had 29.2% deaths over 4.8 years, long-term cumulative hsCRP improved mortality predictions when added to the Get With The Guidelines-HF score and NT-proBNP at baseline, the investigators reported.

In an accompanying editorial, Antonio Abbate, MD, PhD, of the University of Virginia School of Medicine in Charlottesville, and colleagues stressed the role inflammation plays in the development of heart failure and the clinical potential for hsCRP testing.

“Such measurements are simple and cost-effective, making them feasible for routine evaluation in patients with HF [heart failure],” they wrote.

“The results also shed light on the potential mechanisms linking hsCRP to HF progression. Systemic inflammation appears to take a pivotal role in promoting adverse cardiac remodeling and left ventricular dysfunction, ultimately contributing to the worsening of HF. A better understanding of these mechanisms could pave the way for targeted interventions and personalized treatments,” they stated.

The editorialists pointed to recombinant IL-1 receptor antagonist anakinra (Kineret) as an existing anti-inflammatory therapy shown to significantly reduce CRP levels, improve cardiorespiratory fitness, and reduce heart failure-related hospitalizations and heart failure-related mortality.

Similarly, colchicine, another anti-inflammatory recently repurposed for cardiovascular prevention, may hold promise in heart failure, Abbate and colleagues suggested.

For their study, Zhang and colleagues relied on the China PEACE 5p-HF Study, a nationwide cohort study of consecutive patients with acute heart failure enrolled from 52 hospitals in China.

Out of nearly 5,000 patients screened, included in the present report were the 1,281 individuals (median age 64, 35.4% women) who survived the first year after discharge and had sufficient hsCRP results from multiple time points.

The median long-term cumulative hsCRP level from admission to 12 months after discharge was 26 mg/L multiplied by the number of months followed. Over 55% of patients had an excess hsCRP reading in at least two out of the three assessments over the course of the year.

Patients with a higher long-term cumulative hsCRP levels had disproportionately more symptoms, decompensated chronic heart failure, diabetes, anemia, reduced renal function, and higher levels of NT-proBNP, creatinine, leukocytes. They were less likely to be on renin-angiotensin-aldosterone system inhibitors and β-blockers and more likely to be rehospitalized for cardiovascular causes within 12 months.

Study authors acknowledged that their observational analysis does not rule out unmeasured confounding in their results, and there may have been selection bias in people who survived and had sufficient hsCRP readings for the present report.

“Notably, patients included in the final population tended to be younger, have fewer renal and pulmonary comorbidities, and have better left ventricular ejection fraction than patients who were excluded, which raises the interesting hypothesis that assessment of inflammation can be of particular interest for granular stratification of lower-risk subjects,” Abbate’s group wrote.

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