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CASABLANCA: Elevated endothelin-1 levels associated with CV events
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ORLANDO, Fla. — Increased levels of endothelin-1, a vasoconstrictor that is produced by vascular endothelial cells, predicted CV events and mortality in at-risk patients, according to data presented at the American College of Cardiology Scientific Session.
“The biggest take-home is once you identify a certain cohort of patients who are at higher risk, what are the next steps,” Nasrien E. Ibrahim, MD, advanced heart failure and transplant cardiologist and clinical researcher at Massachusetts General Hospital, told Cardiology Today. “The next steps can be more frequent follow-up in these patients, more optimization in their guideline-directed medical therapies, or controlling CV risk factors such as diabetes and obesity. If we can identify such patients, intervening in them sooner and lowering their future risk of cardiovascular events would be very beneficial.”
To analyze the prognostic meaning of endothelin-1, researchers analyzed data from 1,084 patients who were referred for coronary angiography between 2008 and 2011. Endothelin-1 was measured before the procedure.
Follow-up was conducted for a median of 4 years, when patients were monitored for events including MI, incident HF, all-cause mortality and CV mortality.
The median concentration of endothelin-1 was 2.57 pg/mL. Patients whose endothelin-1 concentrations were greater than the median were more likely to have worse renal function, prevalent risk factors for CVD and higher concentrations of N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin ST2 and cystatin C (P < .001 for all).
The presence or severity of CAD was not linked to endothelin-1 concentrations.
Elevated entothelin-1 concentrations predicted incident MI (HR = 1.65; 95%, 1.1-2.48), incident HF (HR = 2.29; 95% CI, 1.66-3.16), all-cause mortality (HR = 2.3; 95% CI, 1.53-3.45), CV mortality (HR = 2.08; 95% CI, 1.26-3.44) and a composite of MI, incident HF and CV mortality (HR = 1.94; 95% CI, 1.47-2.55).
“Specifically with endothelin-1, I would like to look at different cohorts of patients including patients with heart failure with reduced ejection fraction, heart failure with preserved ejection fraction and examining whether in those specific patients, endothelin-1 can predict future risk,” Ibrahim said in an interview. “This is a patient population with high morbidity and mortality, and if we can find something that signals to us that these patients are not going to do well in the future, what can we do now to optimize them to mitigate the risk?” – by Darlene Dobkowski
Reference:
Ibrahim NE, et al. Abstract 1147-085. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Disclosure: The study was funded by Singulex. Ibrahim reports no relevant financial disclosures.
Perspective
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Matthew Jankowich, MD
This study adds to the increasing evidence base that high levels of endothelin-1 are predictors of increased risk for CV morbidity and mortality. Endothelin-1 has now been demonstrated as a risk marker in various disease states and high-risk groups and to some extent in more general population samples.
The findings do not have immediately actionable clinical practice implications, but I hope this study will inspire more examination of endothelin-1 as a biomarker for CVD, and especially to determine whether endothelin-1 can identify patients at risk for future CV events who are not well identified by currently available clinical and laboratory-based risk predictors.
We need to determine whether and to what extent endothelin-1 is a cause or consequence of underlying CVD. Endothelin-1 has complex biologic effects on vascular tone and structure, and we need to know if high levels of endothelin-1 are an adaptive or maladaptive response in patients such as were studied here. Ultimately, we would like to know if CVD and mortality can be prevented in patients with high levels of endothelin-1 by blocking or modifying the effects of endothelin, but that will require well-designed prospective randomized controlled trials.
CV medicine, like other areas in medicine, is moving to more precise and individualized care. Future studies can build on the findings from this study to identify high-risk groups for precision research. However, given that endothelin antagonists have been shown to be ineffective or harmful in certain disease states, aside from pulmonary arterial hypertension, we need to await data from clinical studies before attempting to modify this important biologic pathway in patients without PAH.
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