Coronary Artery Calcification and Complications in Patients With COVID-19.

In the coronavirus disease-2019 (COVID-19) pandemic, early risk stratification of severe forms is essential. Patients with COVID-19 and cardiovascular (CV) risk factors such as hypertension and diabetes have higher morbidity and mortality (1). In patients at high CV risk, coronary artery calcification (CAC) is associated with a higher incidence of nonfatal and fatal outcomes (2). Chest CT has become a key tool for the diagnosis of COVID-19, but CAC detection is not carried out routinely (3). Yet CAC could represent an easy integrative marker of worse prognosis in patients with COVID-19.

From March 15, 2020 to May 3, 2020, we performed a cross-sectional study including consecutive patients hospitalized with COVID-19, 40 to 80 years of age, who underwent noncontrast chest computed tomography on the day of admission. Patients with histories of CV disease were excluded. We analyzed the presence or absence of CAC (CAC+ and CAC−, respectively), defined as any area ≥1 mm2 with density >130 Hounsfield units (HU) on the known coronary tract. Agatston score was also measured, despite technical limitations (no electrocardiographic gating and slice thickness 2.0 mm) (4). Analysis was performed by 2 certified operators blinded to clinical history (1 radiologist and 1 cardiologist). The primary outcome was the first occurrence of mechanical noninvasive or invasive ventilation, extracorporeal membrane oxygenation, or death (scores of 5, 6, and 7 on the World Health Organization Blueprint scale) (5) within 30 days following hospital admission. Because CAC is highly correlated with age, the primary outcome was segmented by median age group. The study was approved by the Paris university hospital ethics committee.

Among 356 patients screened, 147 were excluded (54 had previous CV disease, and 93 did not undergo chest computed tomography within 24 h of admission). Ultimately, 209 consecutive patients were included. The median age was 62 years (interquartile range: 51 to 70 years), 72% were men, and all patients were at grade 3 or 4 on the World Health Organization Blueprint scale at entry (hospitalization without or with nasal oxygen). CAC was detected in 106 patients (50.7%). The primary outcome occurred in 50.0% of CAC+ patients compared with 17.5% of CAC− patients (p < 0.0001) (Figure 1 ). Using Kaplan-Meier analysis, CAC was significantly associated with the primary outcome (hazard ratio [HR]: 3.5; 95% confidence interval [CI]: 2.2 to 5.8; p < 0.0001) (Figure 1). Among patients <62 years of age (n = 104), CAC was detected in 32%, and the primary outcome occurred in 55% of CAC+ patients compared with 20% of CAC− patients (HR: 5.4; 95% CI: 2.4 to 12.2; p < 0.0001). Among patients ≥62 years of age (n = 105), CAC was detected in 69%, and the primary outcome occurred in 48% of CAC+ patients compared with 13% of CAC− patients (HR: 3.2; 95% CI: 1.6 to 6.3; p = 0.02). In a multivariate analysis with a Cox proportional hazards model including age, sex, hypertension, smoking, and diabetes, CAC was independently associated with the primary outcome (HR: 4.4; 95% CI: 2.4 to 8.0; p < 0.0001).

Figure 1

Event Rate and Primary Outcome According to CAC

Event rate and primary outcome (first occurrence of noninvasive or invasive mechanical ventilation, extracorporeal membrane oxygenation [ECMO], or death during hospitalization) according to absence or presence of coronary artery calcification (CAC) on chest computed tomography performed for the diagnosis of coronavirus disease-2019. The cumulative incidences were estimated using Kaplan-Meier analysis. CI = confidence interval.

The median Agatston score was 8 (interquartile range: 0 to 116); 28.7% of patients had Agatston scores >100, and 2.9% had scores >400. The crude HR for the primary outcome for Agatston score (per quartile) was 1.6 (95% CI: 1.3 to 2.0; p < 0.0001), and using the same Cox proportional hazards model, the HR for Agatston score was 1.8 (95% CI: 1.5 to 2.3; p < 0.0001). In CAC+ patients, mean calcification density was 457 ± 176 HU in patients without events, compared with 387 ± 153 HU in patients with events (p = 0.03).

There was 1 acute ST-segment elevation myocardial infarction and no stroke during follow-up. A significant increase in peak high-sensitivity cardiac troponin I was detected in 9.1% of CAC+ patients compared with 3.4% of CAC− patients (p = 0.16).

Our study shows that the presence and extent of CAC are associated with a worse prognosis in hospitalized patients with COVID-19. The severity of immune response, endothelial dysfunction, and myocardial stress due to COVID-19 could be exacerbated in patients with subclinical coronary atherosclerosis.