Introduction:
Endothelial dysfunction may be a phenotypic expression of heart failure (HF). Total brachial artery reactivity (TBAR) is a non-invasive measurement of endothelial function that has been associated with increased risk of cardiovascular outcomes. Limited information is currently available on the impact of TBAR on incident HF and its subtypes. The aim of this study was to evaluate whether TBAR is associated with incident HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF) in a community-based study.
Hypothesis:
We hypothesized that TBAR would be inversely related with incident HF and both HF subtypes.
Methods:
Sample included 5,499 participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. Brachial artery ultrasound was performed after five minutes of cuff occlusion at the right forearm. TBAR was calculated as the difference between maximum and minimum brachial artery diameters following cuff release, divided by the minimum diameter multiplied by 100%. A dichotomous TBAR variable was created based on the median value (below or above 7.9%). Participants with EF ≤ 40% were considered HFrEF and those with EF ≥ 50% were considered HFpEF. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals.
Results:
Over a mean follow-up period of 12.5 years, incident HF was diagnosed in 250 participants; 106 classified as HFpEF, 98 as HFrEF, and 46 with unknown or borderline EF (41-49%). Crude analysis revealed that those with TBAR below the median have significantly higher risk of HF (HR 1.46; 95% CI 1.13-1.88, p<0.01) and HFrEF (HR 1.61; 95% CI 1.07-2.43, p<0.05). Following adjustment for known HF risk factors (e.g. age, gender, race, blood pressure, others), these relationships were no longer statistically significant. Borderline significant results were revealed in those with HFpEF (HR 1.43; 95% CI 0.97-2.12, p=0.06). Kaplan-Meier curves suggest significantly lower risks of developing HF and HFrEF in those with TBAR above the median (log-rank p<0.05 for both). When examined as a continuous variable, with a cut point of 50% for EF, every 1-standard deviation (9.7%) increase in TBAR resulted in a 19% and 29% decrease in risk of HF (p<0.05) and HFrEF (p=0.05), respectively.
Conclusions:
Lower TBAR values were associated with higher rates of incident HF and HFrEF, suggesting a possible role of endothelial dysfunction in HF pathogenesis. The impact of other known HF risk factors may mediate this relationship, thus further research is warranted.
Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis
