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COVID-19 and CAD

The relationship between coronary artery disease and clinical outcomes in COVID-19: a single-center retrospective analysis

Peterson, Erica; Lo, Kevin Bryana; DeJoy, Robert IIIa; Salacup, Gracea; Pelayo, Jeralda; Bhargav, Ruchikaa; Gul, Fahada; Albano, Jeria; Azmaiparashvili, Zuraba; Amanullah, Amana,,b,,c; Patarroyo-Aponte, Gabriela,,b,,d

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doi: 10.1097/MCA.0000000000000934
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Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) typically causes a viral pneumonia with a wide range of complications and has become a global health pandemic since first being reported in December 2019 [1]. The disease has been reported to disproportionately affect those with underlying comorbidities including chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), diabetes mellitus, and hypertension among others [1,2]. The presence of these comorbidities has been shown to be associated with increased likelihood of hospital and ICU admissions, as well as increased mortality [1,2,6].

Evidence of cardiac injury in the form of cardiomyopathies, arrhythmias, and acute coronary syndromes related to COVID-19 has been well described, yet the etiology remains largely unclear. It is suspected that endothelial cell dysfunction, systemic proinflammatory cytokine release, and activation of coagulation pathways result in myocardial injury which may be exacerbated in those with underlying cardiac comorbidities, including CAD [3,4]. CAD has a high prevalence in the United States, affecting 6.7% of adults, and more males than females (7.4% vs 6.2%). Cardiovascular disease accounts for nearly 23% of deaths in the United States, 43% of which are attributable to CAD [5,6]. The primary objective of this study is to describe the clinical outcomes and the interplay of other cardiac and noncardiac comorbid conditions in a high-risk population of patients with COVID-19 infection and CAD compared to those without CAD.


Study design, participants, and data collection

This study was a single-center retrospective analysis of all patients >18 years of age who were admitted to Einstein Medical Center Philadelphia, an urban tertiary care hospital, from 1 March to 24 April 2020, which corresponds to the peak of COVID-19 infections in our area. Patients included had a confirmed diagnosis of COVID-19 via reverse transcriptase–PCR assays (RT-PCR) performed on nasopharyngeal swab specimens. They were then classified according to the presence of a known diagnosis of CAD vs those without CAD. Demographic and clinical data, comorbidities, outcomes, and laboratory findings were obtained. This study was approved by the institutional review board.

Statistical analysis

Demographic variables were presented using descriptive statistics and frequencies. Categorical variables were analyzed with Chi-square testing. Demographic and clinical variables were tabulated. Independent T test was used for continuous variables. For skewed variables, the Mann–Whitney U test was used to compare differences. Multivariate logistic regression analysis was used to evaluate the factors associated with mortality in the overall sample population of patients with COVID-19. 95% confidence intervals (CIs) were used and are presented when appropriate. All analyses were performed using IBM’s SPSS Statistics for Windows, Version 23.0.


Demographic and clinical characteristics of the patients

The study included a total of 389 patients who tested positive via RT-PCR for COVID-19. Thirty-four patients were excluded who were either still inpatient at the time of analysis or had incomplete clinical data on outcomes, leaving a final sample of 355 patients (see Fig. 1). In the final sample of 355 patients, the mean age (±SD) was 66.21 ± 14.21, 49% were female and 70% were African American. Chronic medical conditions of these patients included hypertension (77%), diabetes mellitus (47%), COPD (13%), and asthma (8%). The number of in-hospital deaths was 80 (23%).

Fig. 1:
Flow diagram for the study.

Seventy-seven or 22% of patients had CAD. Patients with CAD were significantly older (72 vs 65, P < 0.0001). There was a higher proportion of females in patients with CAD vs without (57% vs 47%), but this did not reach statistical significance (P = 0.123). There was a significantly higher rate of heart failure among patients with CAD compared to non-CAD group (44% vs 9%, P < 0.0001). The traditional cardiovascular risk factors such as hypertension, diabetes mellitus, and chronic kidney disease (CKD) were significantly higher in patients with CAD. The rates of COPD were also significantly higher in patients with CAD (20% vs 11%, P = 0.043). Among the inflammatory markers, lactate dehydrogenase (LDH) was the only parameter that was significantly different and was found to be lower among patients with CAD vs those without CAD (319 vs 426 IU/L, P = 0.002). Patients with CAD had significantly higher troponin and brain natriuretic peptide (BNP) levels (P < 0.0001) compared to those without CAD. There were significantly more patients above the 99th percentile of the upper range limit (URL) in the CAD group compared to the non-CAD group (62% vs 40%, P = 0.002) (see Table 1). Among patients with significant troponin elevation, over 89% were from nonspecific troponin leaks, while only 11% had actual non-ST elevation myocardial infarction (MI). In terms of clinical outcomes, patients with CAD had a significantly higher risk of inpatient death (31% vs 20%, P = 0.046) and need for renal replacement therapy (33% vs 11%, P < 0.0001) (see Table 1). Looking at the overall patient sample, only age was significantly associated with inpatient mortality (1.041, 95% CI: 1.017–1.066, P = 0.001), while CAD was not independently associated (see Table 2).

Table 1 - Demographic and clinical characteristics of patients
Characteristics CAD (n = 77) No CAD (n = 278) P value
Age (mean ± SD) 72.22 ± 10.27 64.54 ± 14.71 <0.0001
Female gender, % (n) 44 (57) 130 (47) 0.123
Ethnicity, % (n) 0.858
 African American 52 (68) 200 (72)
 Caucasian 8 (10) 19 (7)
 Hispanic 8 (10) 31 (11)
 Other 9 (12) 28 (10)
Comorbidities, % (n)
 BMI (mean ± SD) 28.01 ± 8.18 30.19 ± 9.31 0.065
 COPD 15 (20) 30 (11) 0.043
 Asthma 2 (3) 25 (9) 0.086
 OSA 7 (9) 18 (7) 0.451
 Heart failure 34 (44) 26 (9) <0.0001
 Atrial fibrillation 12 (16) 27 (10) 0.152
 Liver cirrhosis 2 (3) 8 (3) 1.000
 Diabetes 45 (58) 121 (43) 0.028
 Chronic kidney disease 21 (27) 44 (16) 0.03
 End-stage renal disease on dialysis 25 (33) 16 (6) <0.0001
 HIV 2 (3) 5 (2) 0.648
 Hypertension 73 (95) 199 (72) <0.0001
Laboratory/parameters on admission (median IQR)
 FiO2% requirement 21 (21–39) 28 (21–40) 0.158
 Serum ferritin 1061 (359–2712) 783 (334–1677) 0.115
 D-dimer 1940 (1320–3825) 1690 (828–3215) 0.176
 CRP 120 (43–196) 141 (57–219) 0.350
 Procalcitonin 0.41 (0.09–1.51) 0.2 (0.09–0.91) 0.125
 LDH 319 (245–485) 426 (320–576) 0.002
 troponin 0.06 (0.02–0.18) 0.02 (0.01–0.08) <0.0001
 BNP 401 (49–1630) 32 (10–165) <0.0001
COVID-19 treatment
 Hydroxychloroquine 45 (58) 171 (62) 0.693
 Steroids 23 (30) 80 (29) 0.887
 Tocilizumab 5 (7) 38 (14) 0.113
Clinical outcomes
 Inpatient death 24 (31) 56 (20) 0.046
 Need for CRRT/HD 25 (33) 31 (11) <0.0001
 Need for vasopressors 20 (26) 61 (22) 0.447
 Need for intubation 22 (29) 67 (24) 0.459
BNP, brain natriuretic peptide; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; CRP, C-reactive protein,; CRRT/HD, continuous renal replacement therapy/hemodialysis. LDH, lactate dehydrogenase; OSA, obstructive sleep apnea.

Table 2 - Multivariate logistic regression analysis showing factors associated with inpatient mortality among patients with coronavirus disease 2019 in the overall sample population
Characteristics Odds ratio (95% CI) P value
Age 1.041 (1.017–1.066) 0.001
BMI 1.009 (0.975–1.044) 0.611
Male Referrant
Female 1.091 (0.635–1.875) 0.752
African American Referrant
Caucasian 1.157 (0.385–3.482) 0.795
Others 0.992 (0.492–1.997) 0.981
COPD and Asthma 1.024 (0.466–2.249) 0.953
DM 1.367 (0.771–2.424) 0.285
HTN 1.181 (0.544–2.567) 0.674
HF 1.649 (0.765–3.554) 0.202
ESRD on dialysis 0.902 (0.363–2.237) 0.823
Atrial fibrillation 0.475 (0.190–1.188) 0.112
CAD 1.259 (0.635–2.497) 0.509
CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; ESRD, end-stage renal disease; HF, heart failure; HTN, hypertension.


This single-center retrospective study compares the outcomes of patients with confirmed COVID-19 infection and CAD to those without CAD. Recent studies have shown that patients with comorbidities have worse outcomes when suffering from COVID-19 [1,2,7]. However, these studies are predominantly from Asia and Europe, and few of these, even from countries with larger African American populations, report race in their demographics [1,2,8]. Our center serves a predominantly high-risk population, wherein 70% of patients are African American and 11% are Hispanic, and these minority groups are known to have high rates of metabolic disease and risk factors for CAD [5]. Unsurprisingly, the overall prevalence of CAD in our study population was greater than both CAD and cardiovascular diseases as a whole in previously reported studies. In addition, our patients also have higher rates of other comorbidities such as hypertension, diabetes mellitus, COPD, and heart failure [1,2,9–11].

Our findings of increased mortality in patients with CAD and COVID-19 are consistent with prior reports of risk factors associated with both severe disease and increased mortality. There are many proposed mechanisms of the well documented cardiovascular manifestations of COVID-19. Overwhelming inflammation from cytokine storm induced by viral activity may induce cardiomyopathy with pathophysiology like that seen in Takotsubo or stress cardiomyopathy [4,12]. Additionally, cases of severe myocarditis, including those complicated by reduced systolic function have also been reported [13–15]. Though the exact mechanism remains unclear, it is postulated that cardiac myocytes suffer direct viral injury, whether through viral entry or indirect immune response with resultant damage [4,12]. Invasion of the cardiac myocytes by members of SARS-coronavirus family appears to be dependent on the angiotensin converting enzyme 2 (ACE-2) receptors, and viral invasion of myocytes has been documented on autopsy which further supports direct viral entry [14,15]. Moreover, downregulation of ACE-2 receptors by the virus may result in increased levels of the proinflammatory cytokine TNF-α which predisposes the myocardium to damage [1619]. As illustrated with other viral illnesses including influenza, there is a strong association with acute coronary syndrome and viral infections. The sequelae of viral infection (inflammation, immune response, and cytokine activation) promote the progression of atherosclerosis and results in destabilization of plaques in the coronary arteries [20–24].

Any number of these mechanisms may stress the myocardium in patients with CAD and COVID-19 who may or may not already be critically ill and offers one explanation for poorer outcomes in this population. However, as our data suggest CAD is not an independent risk factor for mortality in COVID patients, special attention should be given to other comorbidities and the role they play in COVID mortality. COVID-19 is primarily a respiratory infection, and the most frequently documented outcomes are sepsis/septic shock, respiratory failure, and acute respiratory distress syndrome (ARDS) [1,2,25,26]. As evidenced by our data, it seems less likely that patients with CAD develop more respiratory failure and ARDS as the rate of intubation was not significantly different compared to those without CAD. It seems more likely that sepsis and septic shock, as well as stress from ongoing hypoxemia, may contribute to worsening clinical status in CAD patients. Troponin elevation can reasonably be explained by Type I MI resulting from intracoronary thrombus or plaque rupture [12,16,26]. However, more commonly, it can result from demand ischemia or Type II MI caused by the physiologic stress of systemic vasodilation with resultant hypotension and myocardial oxygen supply–demand mismatch [27,28]. This is consistent with our findings where over 89% of significant troponin elevations in our sample population were nonspecific troponin leaks. Similarly, though our CAD population had higher levels of BNP, there are many mechanisms by which this biomarker may be elevated outside of cardiac dysfunction. Comorbid conditions such as renal failure, advanced age, chronic lung disease, sepsis/critical illness, and shock have been shown to be associated with elevated BNP [29]. Systemic stress of overwhelming infection is consistent with our finding that both the CAD and non-CAD groups had similar end-organ dysfunction as manifested by the need for hemodialysis or CRRT and remains a likely contributor to poor outcomes in patients with CAD. As our CAD population was older with higher rates of comorbid conditions including CKD and chronic lung disease when compared to the non-CAD group, these conditions may be stronger predictive risk factors of mortality in COVID and may attenuate the association of CAD to mortality in patients with COVID-19 [8].

Interestingly, LDH was the only inflammatory marker significantly different and was found to be lower in the CAD group than in the non-CAD group. LDH is a cytoplasmic enzyme found nearly in all cells in the body, and is released when cells are destroyed. It is often elevated in the setting of hemolysis of red blood cells, but has been used as a marker of acute myocardial infarction in the past as well [30]. It is therefore surprising that LDH is lower in our CAD group than in our non-CAD group, when these patients had more severe illness with higher mortality rates. A large cohort study found that an increased LDH may be related to an increased exercise capacity and lower risk of CAD [30]. It is possible that those with underlying CAD or its associated risk factors may have more sedentary lifestyles due to the sequelae of their disease, and thus have lower baseline LDH levels. Regardless, further research is necessary to study the relationship between LDH, CAD, and COVID-19 and the mechanisms involved.


This is a single-center retrospective study and with a predominantly African American population which may limit its generalizability. There was also a higher proportion of females with CAD which is atypical, but it reflects the high-risk nature of our sample population. Although we had a fairly large sample size, the sample population with CAD was relatively small. We included only patients with documented evidence of CAD, which may underestimate CAD prevalence in our study. We also did not include patients who were still admitted at the time of analysis due to lack of outcome data such as mortality and other potentially significant clinical outcomes such as length of stay were not taken into account. Compliance with guideline recommended therapies for CAD were not considered and may influence clinical outcomes.


Compared to those without CAD, patients admitted for COVID-19 infection with concomitant CAD have higher rates of inpatient mortality and need for renal replacement therapy. However, CAD in itself was not independently associated with mortality after adjusting for other covariates suggesting that other factors may play a bigger role in the increased mortality and poor outcomes in these patients.


Conflicts of interest

There are no conflicts of interest.


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coronary artery disease; COVID-19; mortality; novel coronavirus; outcomes

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