C-Reactive Protein and Risk of HF in Patients With CVD

Quick Takes

  • This prospective observational cohort study examined the association between C-reactive protein (CRP), a marker of inflammation, and the incidence of HF in a cohort of 8,089 patients with established cardiovascular disease.
  • Higher CRP levels were significantly associated with an increased long-term risk of incident HF, independent of other risk factors, medication use, and interim MI, and this relationship persisted for over 15 years past the initial CRP measurement.
  • The findings highlight the potential for anti-inflammatory therapies to mitigate this high risk, a premise that requires further exploration through future trials.

Study Questions:

In patients with cardiovascular disease (CVD), are C-reactive protein (CRP) levels associated with incident heart failure (HF)?


The study utilized data from the ongoing prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort, encompassing 8,089 patients with CVD, enrolled between September 1996–January 2019. Patients had various forms of CVD, but no history of HF hospitalization. The study's primary outcome was incident HF, ascertained via linkage to a nationwide hospitalization registry, employing International Classification of Diseases (ICD)-9 and ICD-10 codes. Patients were followed from the time of cohort entry until January 2019. The study also explored mediation of the CRP-HF association by interim myocardial infarction (MI), reverse causality, and the consistency of the association over time.


The median follow-up period was 9.7 years. Among the patients with CRP ≤20 mg/L, there were 768 cases of incident HF (9.8%; incidence rate, 0.98/100 person-years), while in patients with CRP >20 mg/L, there were 42 cases (17.8%; incidence rate, 2.08/100 person-years). A dose-response relationship was apparent between CRP levels and HF, with an especially high risk for patients in the fourth quartile of CRP (4.01-20.0 mg/L): versus first quartile (0.10-0.90 mg/L); hazard ratio (HR), 2.22 (95% confidence interval [CI], 1.76-2.79). Elevated CRP levels were also significantly associated with an increased risk of HF with reduced ejection fraction (HFrEF) (per 1 mg/L: HR, 1.09; 95% CI, 1.04-1.14), and HF with preserved ejection fraction (HFpEF) (HR, 1.12; 95% CI, 1.07-1.18). The association between CRP and incident HF persisted even after adjusting for interim MI. A CRP concentration above the median (>1.90 mg/L) compounded the risk of incident HF in combination with other risk factors, such as MI, diabetes mellitus, smoking, and hypertension. A second measurement of CRP was available for 1,944 patients. In 76% of patients, CRP had changed by <1 standard deviation. Finally, a significant but weak to moderate correlation was found between CRP and white blood cell (WBC) counts. Nevertheless, CRP was found to be more strongly associated with incident HF than WBC counts.


CRP levels are independently associated with incident HF in patients with established CVD.


The investigators leverage a large prospective study with long-term follow-up to perform the most in-depth analysis of the association between CRP and incident HF to date. They notably examine aspects such as the influence of an interim MI, the competing risk of death, and reverse causality. CRP levels were consistently associated with incident HF across subgroups and with a dose-response relationship. The authors conclude that inflammation plays a role in HF and that anti-inflammatory therapies may reduce the risk of HF—a premise that requires further exploration through future trials. Of note, this study does not assess the predictive ability of CRP, nor does it compare it to other biomarkers of inflammation such as soluble urokinase plasminogen activator receptor (suPAR) or interleukin-6 (IL-6), which may be more effective biomarkers of risk in that patient population.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension, Smoking

Keywords: Atherosclerosis, Biomarkers, C-Reactive Protein, Diabetes Mellitus, Heart Failure, Hypertension, Inflammation, Leukocytes, Myocardial Infarction, Primary Prevention, Risk, Secondary Prevention, Smoking, Stroke Volume

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