Increased NT-proBNP levels over time linked to greater risk of heart failure and death

1st March 2023

Increased levels of NT-proBNP over time lead to an elevated risk of both heart failure and mortality among those without heart failure

Increases in the level of N-terminal B-type natriuretic peptide (NT-proBNP) over time are associated with a higher risk of incident heart failure and death among those initially without the disease according to the findings of a study by US researchers.

NT-proBNP levels serve as an important biomarker for patients with chronic heart failure. In fact, higher levels of the protein upon admission to hospital with COVID-19, have also been associated with an increased mortality risk and other complications in patients with and without heart failure. However, in many studies, NT-proBNP has been assessed at a single time-point and in the current work, researchers looked at changes in the biomarker over time and whether this might be prognostic for the development of heart failure among those who were initially free of the disease.

The team used data from the Atherosclerosis in the Communities (ARIC) study and included participants who had measurements of the biomarker at year 2 and 6 (i.e., 4 years apart) but had not been diagnosed with heart failure. The primary exposure variable was the change in NT-proBNP between visits 2 and 4, categorised as either <125 pg/mL or ≥125 pg/mL and the primary outcome measures were set as incident heart failure (HF) hospitalisation and all-cause mortality.

NT-proBNP and risk of heart failure

Data were available for 9,776 individuals (mean age = 57.1 years, 56.5% female) and who were included in the analysis.

Individuals with NT-proBNP levels of 125 pg/mL or higher at both visits had a significantly higher risk of incident HF compared to those with levels below this threshold (adjusted Hazard Ratio, aHR = 2.40, 95% CI 2.00 – 2.88). Similarly, there was an elevated risk of mortality (aHR = 1.68, 95% CI 1.47 – 1.91). Interestingly, those with NT-proBNP levels of 125 pg/mL or higher at visit 2 but which was lower at visit 4, still had a higher risk of HF although the result was not significant (HR = 1.01, 95% 0.71 – 1.43) when compared to those who levels were below the threshold at both visits. There was also a significant increase in HF and mortality risk based on the percent change in the biomarker per 1 standard deviation increase. There were also significant associations with cardiovascular risk factors such as systolic blood pressure, body mass index, triglyceride and low-density lipoprotein cholesterol and the change in NT-proBNP.

The authors concluded that the changes in NT-proBNP over time, reflected a dynamic change in the risk of HF events and death among those without prevalent clinical HF. They added that serial measurements of NT-proBNP could be use to improve risk stratification of patients pre-heart failure.

Citation
Jia X et al. Association of Long-term Change in N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure and Death. JAMA Cardiol 2023

Heart failure patients at increased risk of cancer and cancer-related mortality

28th January 2022

Heart failure patients greater than 50 years of age have been found to be at a higher risk of cancer and cancer-related mortality

Heart failure (HF) patients have a higher risk of cancer and cancer-related mortality compared to matched-controls according to research by a team from the Cardiovascular Disease Unit, Genoa, Italy.

There is emerging evidence that the incidence of cancer is higher among those with cardiovascular disease and heart failure and this latter group frequently die from cancer. In fact, research has uncovered the increased risk of cancer among HF patients, persists beyond the first year after their HF diagnosis and that their prognosis is worse compared to non-heart failure patients with cancer.

Despite this purported association, other work among 28,341 Physicians’ Health Study participants, has shown that HF is not associated with an increased risk of cancer among male physicians. It has also been suggested that while heart failure patients did have a slightly increased risk of various cancer subtypes, these increased risks were largely drive by comorbidities.

Given this potential uncertainty over the HF-cancer association, the Italian team attempted to provide greater clarity by undertaking a retrospective cohort study of healthcare records in Puglia, a region of southern Italy. They included patients aged 50 years and older, diagnosed with heart failure but without a history of cancer in the three years prior to their inclusion in the analysis.

The team included a control group without HF who were matched on age and sex. The primary outcomes of the study were cancer incidence as well as mortality. In an effort to examine whether HF severity influenced the study outcomes, the researchers also explored patients use of doses in excess of 80 mg/day of furosemide and equivalents for longer than 30 days in the year before the index date.

Heart failure patients and cancer

A total of 104,020 HF patients with a mean age of 76 years were matched to an equal number of control patients. The researchers identified a total of 12,036 new diagnoses of cancer in HF patients and 7,045 in controls after a median follow-up period of 5 years. This gave an incidence cancer rate of 21.36 per 1000 person-years among those with HF and 12.42 in the control arm (Hazard ratio, HR = 1.76, 95% CI 1.71 – 1.81).

The cancer mortality rate was also higher among HF patients compared with controls (HR = 4.11, 95% CI 3.86 – 4.38). This difference was also seen among HF patients aged less than 70 years (HR = 1.66, 95% CI 1.58 – 1.75) and in those over 80 years of age (HR = 2.07).

High dose loop diuretics also showed an important effect with a higher cancer incidence (HR = 1.11, 95% CI 1.03 – 1.21) and cancer-related mortality (HR = 1.35).

The authors concluded that HF patients had both a higher incidence of cancer and cancer mortality than matched controls and speculated that given that the risk was elevated among those with high dose loop diuretics, it was possible that the overall cancer risks were potentially higher in those with decompensated, i.e., more severe HF.

Citation

Bertero E et al. Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort JACC CardioOncology 2022

Sex-related heart failure mortality influenced by left ventricular ejection fraction

4th January 2022

Sex-related differences in mortality after heart-failure hospitalisation is influenced by the left ventricular ejection fraction

Sex-related differences in mortality in patients with heart failure hospitalisations appear to be affected by the left ventricular ejection fraction according to researchers from the Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Although the risk of heart failure (HF) is similar between men and women, there are some notable sex-related differences, with men being predisposed to HF with reduced ejection fraction and women with preserved ejection fraction.

Although there is some evidence that women with HF live longer than men, they experience more psychological and physical disability. However, much of the available data is derived from patients with stable HF and what is less clear, is if there are any sex-related prognostic differences among patients hospitalised following decompensated heart failure.

For the present study, the Spanish team retrospectively examined gender differences in mortality across the left ventricular ejection fraction spectrum in a cohort of patients after a hospitalisation for acute HF.

The researchers used a multi-centre prospective registry of those hospitalised and collected demographics, medical history, laboratory and echocardiographic parameters and followed patients over a 6-month period.

The primary study endpoints were all-cause, cardiovascular and HF-related mortality. Cardiovascular death was considered secondary to a worsening of HF, acute myocardial infarction, stroke or transient ischaemic attack, whereas HF-related deaths were considered secondary to a worsening of the HF or a sudden cardiac death.

Findings

A total of 4812 patients with a mean age of 74.2 years (46.6% women) were included in the analysis. The proportion of patients with a left ventricular ejection fraction (LVEF) of < 40%, 41 – 49% and > 50% was 31.5%, 14.3% and 54.2% respectively. Women were generally older with a mean age of 76.8 years compared to 71.9 years for men and had a higher preserved ejection fraction (70.5% vs 39.9%, female vs male, p < 0.001).

After 6 months, 645 (13.4%) of the patients had died with mortality rates of 13.3% and 13.5% (women vs men, p = 0.82) and there were no significant sex-related differences in all-cause mortality. Moreover, LVEF was not an independent predictor of mortality (HR = 1.02, 95% CI 0.99 – 1.05, p = 0.13). Similarly, rates of cardiovascular mortality were not different between the sexes.

However, there was a significant interaction between sex and levels of LVEF (p for interaction = 0.030) and women had a significantly lower risk of cardiovascular mortality at lower LVEF levels (< 25%). There were also no differences between the sexes in HF-related mortality although as with cardiovascular mortality, there were differences across the levels of LVEF and women had a reduced risk of HR-related death.

For example, compared to men, women had a reduced risk of HF death at a LVEF of < 43% (HR = 0.77, 95% CI 0.59 – 0.99) In contrast, this risk of death in women became higher as the LVEF increased above 80%.

Commenting on these findings, the authors noted that while sex was not a determinant of 6 month all-cause mortality, women had a lower risk of cardiovascular and HR-related mortality where the LVEF was < 25% and < 43% but higher where the LVEF was > 80%.

They concluded that further work is required to confirm these findings and to evaluate the potential negative implications of a supra-normal LVEF in women with a preserved ejection fraction.

Citation

Santas E et al. Sex-Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum J Am Heart Assoc 2021.