Subclinical Atherosclerosis Burden Shapes All-Cause Mortality Risk

Valentin Fuster, MD, PhD

Credit: Mount Sinai

Subclinical atherosclerosis burden and progression were independently linked to all-cause mortality risk in asymptomatic individuals without previous clinical cardiovascular disease (CVD), according to a new study in the Journal of the American College of Cardiology.¹

The study population, comprised of 5716 adults enrolled between 2008 and 2009 in the BioIMage study, underwent examination by vascular ultrasound (VUS) to quantify carotid plaque burden (cPB) and by computed tomography (CT) for coronary artery calcium (CAC) scores.

“Carotid plaque is an accumulation of cholesterol, calcium, and other circulating substances that are deposited in the blood vessel wall,” said Ana García Álvarez, MD, PhD, a Centro Nacional de Investigaciones Cardiovasculares (CNIC) group leader and head of the cardiology service at Hospital Clínic Barcelona.² “The formation of these plaques can narrow or block the carotid arteries, reducing blood flow to the brain and increasing the risk of a cerebrovascular accident or stroke.”

The underlying processes of atherosclerosis typically precede clinical manifestations of CVD, the leading cause of global mortality.³ CV risk prediction for the population level is often based on conventional cardiovascular risk factors but exhibits limited accuracy for individual long-term risk prediction.

Visualization and quantification methods of subclinical atherosclerosis using noninvasive vascular images have garnered an expanding role in CV risk assessment—it has been further improved by measuring not just the visualization of, but the extent of atherosclerotic burden, defined by the CAC score or VUS-detected cPB.

However, there are limited data on whether the quantification of atherosclerosis extent and progression can predict all-cause mortality risk among a population of asymptomatic individuals. The investigative team, led by Valentin Fuster, MD, PhD, director of the cardiovascular institute, physician-in-chief at Mount Sinai Medical Center, and general director of the CNIC, evaluated the independent predictive value of subclinical atherosclerosis burden, beyond traditional cardiovascular risk factors.¹

“The long asymptomatic phase of the disease presents a window of opportunity that has not been exploited in the younger population,” Fuster said.²

The full study population underwent the imaging arm of the study and was assessed by carotid VUS and CAC scoring—732 participants underwent a second, follow-up carotid VUS a median of 8.9 years after the baseline exam.¹ Participants were followed until October 2021, with all-cause mortality as the primary outcome.

Across a median of 12.4 years of follow-up, 901 (16%) of the study population died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC scores remained significantly associated with all-cause mortality (fully adjusted trend hazard ratio [HR], 1.23; 95% CI, 1.16–1.32; and HR, 1.15; 95% CI, 1.08–1.23), respectively (both P <.001). Overall, the performance favored cPB over the CAC score.

Among the subgroup with a follow-up carotid VUS nearly 9 years after baseline, the median cPB progressed from 29.2 to 91.3 mm3. Investigators identified a significant association between cPB progression and all-cause mortality, which remained after adjusting for cardiovascular risk factors and baseline cPB (HR, 1.03; 95% CI, 1.01–1.04 per absolute 10-mm3 change; P = .01).

“[VUS] is a noninvasive and affordable test, and the valuable prognostic information it provides can be used to improve risk stratification and to target lifestyle recommendations for the control of cardiovascular risk factors”, said Borja Ibáñez, MD, PhD, scientific director at CNIC and a cardiologist at Fundación Jiménez Díaz.²

References

1. _{Valentin Fuster MD, a, b, et al. Influence of subclinical atherosclerosis burden and progression on mortality. Journal of the American College of Cardiology. September 30, 2024. Accessed September 30, 2024. https://www.sciencedirect.com/science/article/pii/S0735109724080963?via%3Dihub.}
2. _{CNIC_CARDIO. Progression of subclinical atherosclerosis predicts all-cause mortality risk. EurekAlert! September 30, 2024. Accessed October 1, 2024. https://www.eurekalert.org/news-releases/1059352.}
3. _{Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association [published correction appears in Circulation. 2022 Sep 6;146(10):e141. doi: 10.1161/CIR.0000000000001074]. Circulation. 2022;145(8):e153-e639. doi:10.1161/CIR.0000000000001052}