Association Between the 10-Year ASCVD Risk Score and COVID-19 Complications Among Healthy Adults (Analysis from the National Cohort COVID Collaborative)
2023; Elsevier BV; Volume: 202; Linguagem: Inglês
10.1016/j.amjcard.2023.05.012
ISSN1879-1913
AutoresRasha Khatib, Nicole Glowacki, Julie C. Lauffenburger, Alex Reddy, Kate Dennert, David Triscari,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoCOVID-19 complications have been linked to worse outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Less is known about the cumulative consequences of multiple ASCVD risk factors on COVID-19 outcomes. We evaluated the dose-response associations between 10-year ASCVD risk scores and COVID-19 complications. The National COVID-19 Cohort Collaborative collects electronic health record data from over 70 US health systems. Our analysis was limited to patients with positive COVID-19 tests without documented ASCVD events at the time of the first positive test. We evaluated the dose-response associations between 10-year ASCVD risk scores, categorized into categorized as low ( 20.0%), and COVID-19 complications, including hospitalizations and mortality. We reported the outcomes using multivariable-adjusted hazard ratios and 95% confidence intervals (CIs). Our cohort included 120,335 patients with documented positive COVID-19 test results who were free of ASCVD events. The mean age was 51.9 ± 16.1 years, 59.4% were women, 15.3% were Black, and 13.7% were Hispanic/Latino. Overall, 15,363 patients (12.8%) were hospitalized and 2,058 (1.7%) died. Patients at intermediate risk of developing ASCVD were had a 1.49 (95% CI 1.41 to 1.56) increased risk of hospitalization and 1.77 (95% CI 1.76 to 1.79) increased risk of mortality compared with patients at low risk. Patients at high risk had a 2.23 (95% CI 2.10 to 2.38) increased risk of hospitalization and a 5.98 (95% CI 5.93 to 6.03) increased risk of mortality. In conclusion, patients in this nationwide cohort at high risk of developing ASCVD are at substantially greater risk of COVID-19 complications. COVID-19 mitigation efforts should focus on these patient populations. COVID-19 complications have been linked to worse outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Less is known about the cumulative consequences of multiple ASCVD risk factors on COVID-19 outcomes. We evaluated the dose-response associations between 10-year ASCVD risk scores and COVID-19 complications. The National COVID-19 Cohort Collaborative collects electronic health record data from over 70 US health systems. Our analysis was limited to patients with positive COVID-19 tests without documented ASCVD events at the time of the first positive test. We evaluated the dose-response associations between 10-year ASCVD risk scores, categorized into categorized as low ( 20.0%), and COVID-19 complications, including hospitalizations and mortality. We reported the outcomes using multivariable-adjusted hazard ratios and 95% confidence intervals (CIs). Our cohort included 120,335 patients with documented positive COVID-19 test results who were free of ASCVD events. The mean age was 51.9 ± 16.1 years, 59.4% were women, 15.3% were Black, and 13.7% were Hispanic/Latino. Overall, 15,363 patients (12.8%) were hospitalized and 2,058 (1.7%) died. Patients at intermediate risk of developing ASCVD were had a 1.49 (95% CI 1.41 to 1.56) increased risk of hospitalization and 1.77 (95% CI 1.76 to 1.79) increased risk of mortality compared with patients at low risk. Patients at high risk had a 2.23 (95% CI 2.10 to 2.38) increased risk of hospitalization and a 5.98 (95% CI 5.93 to 6.03) increased risk of mortality. In conclusion, patients in this nationwide cohort at high risk of developing ASCVD are at substantially greater risk of COVID-19 complications. COVID-19 mitigation efforts should focus on these patient populations. COVID-19 has become one of the leading causes of global mortality, with a disproportionate impact on older patients with underlying conditions, particularly atherosclerotic cardiovascular disease (ASCVD), which, for decades, has been the dominant cause of total cardiovascular disease mortality.1Guan WJ Ni ZY Hu Y Liang WH Ou CQ He JX Liu L Shan H Lei CL Hui DSC Du B Li LJ Zeng G Yuen KY Chen RC Tang CL Wang T Chen PY Xiang J Li SY Wang JL Liang ZJ Peng YX Wei L Liu Y Hu YH Peng P Wang JM Liu JY Chen Z Li G Zheng ZJ Qiu SQ Luo J Ye CJ Zhu SY Zhong NS China Medical Treatment Expert Group for COVID-19Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (18830) Google Scholar Given that ASCVD is a leading cause of death worldwide, several reports have evaluated and identified the clear associations between worse COVID-19 outcomes and established ASCVD.1Guan WJ Ni ZY Hu Y Liang WH Ou CQ He JX Liu L Shan H Lei CL Hui DSC Du B Li LJ Zeng G Yuen KY Chen RC Tang CL Wang T Chen PY Xiang J Li SY Wang JL Liang ZJ Peng YX Wei L Liu Y Hu YH Peng P Wang JM Liu JY Chen Z Li G Zheng ZJ Qiu SQ Luo J Ye CJ Zhu SY Zhong NS China Medical Treatment Expert Group for COVID-19Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (18830) Google Scholar,2Bonow RO Fonarow GC O'gara PT Yancy CW Association of coronavirus disease 2019 (COVID-19) with myocardial injury and mortality.JAMA Cardiol. 2020; 5: 751-753Crossref PubMed Scopus (387) Google Scholar To classify the levels of ASCVD risk, the American Heart Association and American College of Cardiology developed a comprehensive pooled cohort risk equation to predict the 10-year risk of developing ASCVD in the general population.3Goff Jr, DC Lloyd-Jones DM Bennett G Coady S D'Agostino RB Gibbons R Greenland P Lackland DT Levy D O'Donnell CJ Robinson JG Schwartz JS Shero ST Smith Jr, SC Sorlie P Stone NJ Wilson PW Jordan HS Nevo L Wnek J Anderson JL Halperin JL Albert NM Bozkurt B Brindis RG Curtis LH DeMets D Hochman JS Kovacs RJ Ohman EM Pressler SJ Sellke FW Shen WK Smith Jr, SC Tomaselli GF American College of Cardiology/American Heart Association Task Force on Practice Guidelines/American Heart Association Task Force on Practice2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014; 129: S49-S73Crossref PubMed Scopus (2505) Google Scholar Although some studies have explored the associations between the patients' ASCVD risk factors and COVID-19 complications,4Ebinger JE Driver M Joung S Tran T Barajas D Wu M Botting PG Navarrette J Sun N Cheng S. Hypertension and excess risk for Severe COVID-19 illness despite booster vaccination.Hypertension. 2022; 79: e132-e134Crossref Scopus (6) Google Scholar,5Sun Y Guan X Jia L Xing N Cheng L Liu B Zhang S He K. Independent and combined effects of hypertension and diabetes on clinical outcomes in patients with COVID-19: A retrospective cohort study of Huoshen Mountain Hospital and Guanggu Fangcang Shelter Hospital.J Clin Hypertens (Greenwich). 2021; 23: 218-231Crossref PubMed Scopus (12) Google Scholar the associations between the cumulative consequences of multiple ASCVD risk factors have not been extensively evaluated. Thus, we aimed to evaluate the association between the ASCVD risk score and COVID-19 outcomes, specifically, hospitalization and mortality. Given that a quarter of the US population is at intermediate risk of developing ASCVD in the future,6Vega GL Wang J Grundy SM. Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.J Clin Lipidol. 2022; 16: 66-74Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar evaluating across levels of ASCVD risk is important. Previous studies were limited in terms of geography or health care system representation. We used data from the National COVID Cohort Collaborative (N3C) enclave, which harmonizes data across multiple health care systems and clinical sites in the United States and is curated centrally to ensure quality and consistency across sites7Bennett TD Moffitt RA Hajagos JG Amor B Anand A Bissell MM Bradwell KR Bremer C Byrd JB Denham A DeWitt PE Gabriel D Garibaldi BT Girvin AT Guinney J Hill EL Hong SS Jimenez H Kavuluru R Kostka K Lehmann HP Levitt E Mallipattu SK Manna A McMurry JA Morris M Muschelli J Neumann AJ Palchuk MB Pfaff ER Qian Z Qureshi N Russell S Spratt H Walden A Williams AE Wooldridge JT Yoo YJ Zhang XT Zhu RL Austin CP Saltz JH Gersing KR Haendel MA Chute CG National COVID Cohort Collaborative (N3C) ConsortiumClinical characterization and prediction of clinical severity of SARS-CoV-2 infection among US adults using data from the US National COVID Cohort Collaborative.JAMA Netw Open. 2021; 4e2116901Crossref Scopus (101) Google Scholar, making this one of the largest studies to evaluate the associations between ASCVD risk factors and COVID-19 severity.8Haendel MA Chute CG Bennett TD Eichmann DA Guinney J Kibbe WA Payne PRO Pfaff ER Robinson PN Saltz JH Spratt H Suver C Wilbanks J Wilcox AB Williams AE Wu C Blacketer C Bradford RL Cimino JJ Clark M Colmenares EW Francis PA Gabriel D Graves A Hemadri R Hong SS Hripscak G Jiao D Klann JG Kostka K Lee AM Lehmann HP Lingrey L Miller RT Morris M Murphy SN Natarajan K Palchuk MB Sheikh U Solbrig H Visweswaran S Walden A Walters KM Weber GM Zhang XT Zhu RL Amor B Girvin AT Manna A Qureshi N Kurilla MG Michael SG Portilla LM Rutter JL Austin CP Gersing KR Consortium NC. The National COVID Cohort Collaborative (N3C): rationale, design, infrastructure, and deployment.J Am Med Inform Assoc. 2021; 28: 427-443Crossref PubMed Scopus (167) Google Scholar The N3C patient population is also highly diverse in terms of race and ethnicity and therefore, results can be generalized to Black patients and Hispanic/Latino populations who have been at a greater risk of COVID-19 infections and adverse outcomes.9Azar KMJ Shen Z Romanelli RJ Lockhart SH Smits K Robinson S Brown S Pressman AR. Disparities in outcomes among COVID-19 patients in A Large Health Care System in California.Health Aff (Millwood). 2020; 39: 1253-1262Crossref PubMed Scopus (391) Google Scholar We used a limited data set from the N3C database, which contains deidentified data, 5-digit patient ZIP codes, and exact dates of COVID-19 diagnoses and service use. Institutional review board approval and a waiver of written informed consent for this retrospective cohort study were provided by the Advocate Aurora Health Institutional Review Board. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines to present our results. N3C structure, access, and analytic capabilities have been described in detail previously.7Bennett TD Moffitt RA Hajagos JG Amor B Anand A Bissell MM Bradwell KR Bremer C Byrd JB Denham A DeWitt PE Gabriel D Garibaldi BT Girvin AT Guinney J Hill EL Hong SS Jimenez H Kavuluru R Kostka K Lehmann HP Levitt E Mallipattu SK Manna A McMurry JA Morris M Muschelli J Neumann AJ Palchuk MB Pfaff ER Qian Z Qureshi N Russell S Spratt H Walden A Williams AE Wooldridge JT Yoo YJ Zhang XT Zhu RL Austin CP Saltz JH Gersing KR Haendel MA Chute CG National COVID Cohort Collaborative (N3C) ConsortiumClinical characterization and prediction of clinical severity of SARS-CoV-2 infection among US adults using data from the US National COVID Cohort Collaborative.JAMA Netw Open. 2021; 4e2116901Crossref Scopus (101) Google Scholar,8Haendel MA Chute CG Bennett TD Eichmann DA Guinney J Kibbe WA Payne PRO Pfaff ER Robinson PN Saltz JH Spratt H Suver C Wilbanks J Wilcox AB Williams AE Wu C Blacketer C Bradford RL Cimino JJ Clark M Colmenares EW Francis PA Gabriel D Graves A Hemadri R Hong SS Hripscak G Jiao D Klann JG Kostka K Lee AM Lehmann HP Lingrey L Miller RT Morris M Murphy SN Natarajan K Palchuk MB Sheikh U Solbrig H Visweswaran S Walden A Walters KM Weber GM Zhang XT Zhu RL Amor B Girvin AT Manna A Qureshi N Kurilla MG Michael SG Portilla LM Rutter JL Austin CP Gersing KR Consortium NC. The National COVID Cohort Collaborative (N3C): rationale, design, infrastructure, and deployment.J Am Med Inform Assoc. 2021; 28: 427-443Crossref PubMed Scopus (167) Google Scholar,10U.S. Department of Health and Human Services, National Institutes of Health, National Center for Advancing Translational Sciences (NCATS). National COVID Cohort Collaborative Data enclave repository. Available at: https://ncats.nih.gov/n3c. Accessed on August 4, 2020.Google Scholar In brief, the N3C collects patient-level information from the electronic health record (EHR) of 70 health systems across the United States on clinical encounters occurring on or after January 1, 2020. Patients are included in the cohort if they have a documented International Classification of Diseases, Tenth Revision, Clinical Modification COVID-19 diagnosis code (U07.1) or a SARS-CoV‐2 polymerase chain reaction or antigen test documented in the EHR.7Bennett TD Moffitt RA Hajagos JG Amor B Anand A Bissell MM Bradwell KR Bremer C Byrd JB Denham A DeWitt PE Gabriel D Garibaldi BT Girvin AT Guinney J Hill EL Hong SS Jimenez H Kavuluru R Kostka K Lehmann HP Levitt E Mallipattu SK Manna A McMurry JA Morris M Muschelli J Neumann AJ Palchuk MB Pfaff ER Qian Z Qureshi N Russell S Spratt H Walden A Williams AE Wooldridge JT Yoo YJ Zhang XT Zhu RL Austin CP Saltz JH Gersing KR Haendel MA Chute CG National COVID Cohort Collaborative (N3C) ConsortiumClinical characterization and prediction of clinical severity of SARS-CoV-2 infection among US adults using data from the US National COVID Cohort Collaborative.JAMA Netw Open. 2021; 4e2116901Crossref Scopus (101) Google Scholar Data on eligible patients are collected from each health care system longitudinally, including a look back to document patient clinical history, and is harmonized and stored in the N3C data enclave.11Grundy SM Stone NJ Bailey AL Beam C Birtcher KK Blumenthal RS Braun LT de Ferranti S Faiella-Tommasino J Forman DE Goldberg R Heidenreich PA Hlatky MA Jones DW Lloyd-Jones D Lopez-Pajares N Ndumele CE Orringer CE Peralta CA Saseen JJ Smith Jr, SC Sperling L Virani SS Yeboah J 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines.J Am Coll Cardiol. 2019; 73: e285-e350Crossref PubMed Scopus (1301) Google Scholar Our analysis includes adult patients (aged ≥18 years) with a first positive COVID-19 polymerase chain reaction or antigen test between January 1, 2020 and September 30, 2021. Patients with a negative laboratory COVID-19 test and patients who only have a documented COVID-19 diagnostic code without a laboratory confirmation were excluded. To calculate the 10-year ASCVD risk score, the cohort was further defined by excluding patients with a history of ASCVD, defined using the International Classification of Diseases, Tenth Revision codes for acute myocardial infarction, angina, coronary artery disease, coronary revascularization, ischemic stroke, peripheral arterial disease, or transient ischemic attack.11Grundy SM Stone NJ Bailey AL Beam C Birtcher KK Blumenthal RS Braun LT de Ferranti S Faiella-Tommasino J Forman DE Goldberg R Heidenreich PA Hlatky MA Jones DW Lloyd-Jones D Lopez-Pajares N Ndumele CE Orringer CE Peralta CA Saseen JJ Smith Jr, SC Sperling L Virani SS Yeboah J 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines.J Am Coll Cardiol. 2019; 73: e285-e350Crossref PubMed Scopus (1301) Google Scholar Sites with poor reporting on the ASCVD risk score components were excluded. Patients from the remaining sites were further excluded if they were missing any of the score components. Supplementary Appendix 1 presents a map of the United States, highlighting the states included in this analysis. The study outcomes were 14-day hospitalization and 90-day mortality documented in the EHR. Hospitalization was defined as patients hospitalized at the time of the COVID-19–positive laboratory test results or up to 14 days after the test result. We limited the hospitalization definition to 14 days to ensure that patients were hospitalized because of COVID-19 complications as reported in previous studies.12Kahkoska AR Abrahamsen TJ Alexander GC Bennett TD Chute CG Haendel MA Klein KR Mehta H Miller JD Moffitt RA Stürmer T Kvist K Buse JB N3C ConsortiumAssociation between glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor use and COVID-19 outcomes.Diabetes Care. 2021; 44: 1564-1572Crossref PubMed Scopus (4) Google Scholar Mortality was defined based on deaths documented within 90 days of the patient's first COVID-19–positive laboratory test. This cutoff is consistent with other studies exploring COVID-19 mortality.13Ge J Pletcher MJ Lai JC N3C ConsortiumOutcomes of SARS-CoV-2 infection in patients with chronic liver disease and cirrhosis: a National COVID Cohort Collaborative study.Gastroenterology. 2021; 161 (e5): 1487-1501Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The primary independent variable was the ASCVD risk score using the American College of Cardiology/American Heart Association ASCVD pooled cohort risk equations, categorized as low ( 20.0%).14Muntner P Colantonio LD Cushman M Goff Jr, DC Howard G Howard VJ Kissela B Levitan EB Lloyd-Jones DM Safford MM Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations.JAMA. 2014; 311: 1406-1415Crossref PubMed Scopus (415) Google Scholar The score was calculated using the "ascvd_10y_accaha" code provided for the score calculation within the N3C database, which follows the 2013 guidelines for score calculation.3Goff Jr, DC Lloyd-Jones DM Bennett G Coady S D'Agostino RB Gibbons R Greenland P Lackland DT Levy D O'Donnell CJ Robinson JG Schwartz JS Shero ST Smith Jr, SC Sorlie P Stone NJ Wilson PW Jordan HS Nevo L Wnek J Anderson JL Halperin JL Albert NM Bozkurt B Brindis RG Curtis LH DeMets D Hochman JS Kovacs RJ Ohman EM Pressler SJ Sellke FW Shen WK Smith Jr, SC Tomaselli GF American College of Cardiology/American Heart Association Task Force on Practice Guidelines/American Heart Association Task Force on Practice2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014; 129: S49-S73Crossref PubMed Scopus (2505) Google Scholar,15Castro V. Compute Risk Scores for Cardiovascular Diseases. version 1.1.0, package ACC/AHA; 2013 ASCVD risk score [website]. Available at: https://cran.r-project.org/web/packages/CVrisk/CVrisk.pdf. Accessed on August 4, 2020.Google Scholar The score components were based on the most recent values documented in the EHR before or on the day of the COVID-19 laboratory test result. The secondary independent variables include the individual components of the risk score and were categorized as defined in previous studies on what is considered clinically controlled or uncontrolled. Systolic blood pressure was categorized as <140 versus ≥140 mm Hg,16Whelton PK Carey RM Aronow WS Casey Jr, DE Collins KJ Dennison Himmelfarb C DePalma SM Gidding S Jamerson KA Jones DW MacLaughlin EJ Muntner P Ovbiagele B Smith Jr, SC Spencer CC Stafford RS Taler SJ Thomas RJ Williams Sr, KA Williamson JD Wright Jr, JT 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2018; 138: e484-e594Crossref PubMed Scopus (361) Google Scholar total cholesterol was categorized as <200 versus ≥200 mg/100 ml,17Grundy SM Cleeman JI Merz CN Brewer Jr, HB Clark LT Hunninghake DB Pasternak RC Smith Jr, SC Stone NJ National Heart, Lung, and Blood InstituteAmerican College of Cardiology FoundationAmerican Heart AssociationImplications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation. 2004; 110: 227-239Crossref PubMed Scopus (5096) Google Scholar and high-density lipoprotein (HDL) was categorized as <60 versus ≥60 mg/100 ml.11Grundy SM Stone NJ Bailey AL Beam C Birtcher KK Blumenthal RS Braun LT de Ferranti S Faiella-Tommasino J Forman DE Goldberg R Heidenreich PA Hlatky MA Jones DW Lloyd-Jones D Lopez-Pajares N Ndumele CE Orringer CE Peralta CA Saseen JJ Smith Jr, SC Sperling L Virani SS Yeboah J 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines.J Am Coll Cardiol. 2019; 73: e285-e350Crossref PubMed Scopus (1301) Google Scholar History of diabetes was defined based on International Classification of Diseases, Tenth Revision codes. Blood pressure–lowering therapy included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β blockers, calcium channel blockers, thiazide diuretics, and other blood pressure–lowering therapies and was categorized as at least 1 therapy versus none. Smoking status was categorized as yes or no based on the current smoking status. Age was categorized based on the mean age of the cohort as <52 versus ≥52 years. Race and ethnicity were combined, referred herein as race/ethnicity. Other covariates include the calendar year of the COVID-19 test (2020, which is when the pandemic just started, and our knowledge of the clinical course was limited versus 2021 when the COVID-19 vaccination became available, and we knew a lot more about treating the infection) and the site that contributed the data. Analyses were performed within the N3C Enclave using SQL, Python, and R., in accordance with N3C privacy and download review policies. Categorical variables are shown as frequency rates and percentages and continuous variables as mean (SD) and median (interquartile range). Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (CIs) for the association of ASCVD risk scores and categories (low, intermediate, and high) with the 2 primary outcomes: 14-day hospitalizations, and 90-day mortality. Additional Cox proportional hazards regression models were created for the association of individual ASCVD risk score components with each of the primary outcomes. A total of 2,731,465 patients from 38 sites had a confirmed positive COVID-19 laboratory test. Twenty of these sites (1,469,852 patients) did not provide sufficient values to calculate the ASCVD risk score and were excluded. An additional 129,881 patients were excluded because they had documented a history of ASCVD before the date of the positive COVID-19 test. Given that the primary predictor of the study is the ASCVD risk score we further limited to analysis cohort to patients with complete score components, leaving 120,335 patients from 18 sites for this analysis (Figure 1). The mean age of the analysis cohort was 51.9 ± 16.1 years, 59.4% were women, 15.3% were Black, and 13.7% were Hispanic/Latino. Half of the cohort (55.2%) were at a low risk of developing ASCVD in the next 10 years, 24.8% were at an intermediate risk, and 20.0% were at a high risk (Table 1). Patients included in the analysis were older than the excluded patients but had similar gender and race/ethnicity breakdown (Supplementary Appendix 2). The analysis cohort remains generalizable, especially because other US cohorts report similar breakdowns of the ASCVD risk score categories.6Vega GL Wang J Grundy SM. Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.J Clin Lipidol. 2022; 16: 66-74Abstract Full Text Full Text PDF PubMed Scopus (2) Google ScholarTable 1Patient characteristics by 10-year ASCVD risk scoreLow Risk( 20.0%)OverallN=66,409 (55.2%)N=29,848 (24.8%)N=24,078 (20.0%)N=120,335N (%)N (%)N (%)N (%)Age (Mean ± Standard Deviation)42.3±11.758.1±10.170.8±11.951.9+16.1Sex Male21,425 (32.3%)15,147 (50.7%)12306 (51.1%)48,878 (40.6%) Female44,984 (67.7%)14,701 (49.3%)11,772 (48.9%)71,457 (59.4%)Race/Ethnicity White39,154 (59.0%)17,143 (57.4%)12,984 (53.9%)69,281 (57.6%) Black8217 (12.4%)5,063 (17.0%)5,158 (21.4%)18,438 (15.3%) Hispanic/ Latino8,827 (13.3%)4,145 (13.9%)3,555 (14.8%)16,527 (13.7%) Other/ Unknown10,2011 (15.4%)3,497 (11.7%)2,381 (9.9%)16,089 (13.4%)Time of COVID-19 Test 202040,088 (60.4%)18,115 (60.7%)14,743 (61.2%)72,946 (60.6%) 202126,321 (39.6%)11,733 (39.3%)9,335 (38.7%)47,389 (39.4%)Testing Location Outpatient22,388 (33.7%)9,897 (33.2%)6,884 (28.6%)39,175 (32.6%) Inpatient3,979 (6.0%)3,173 (10.6%)4,382 (18.20%)11,515 (9.6%) Other/ Unknown40,042 (60.3%)16,778 (56.2%)12,812 (53.2%)69,645 (57.9%) Open table in a new tab A total of 15,363 patients (12.8%) were hospitalized within 14 days of diagnosis. Among patients with a low ASCVD risk score, 8.6% were hospitalized, which increased to 14.0% among patients with an intermediate score and 22.6% among patients with a high score. A total of 2,058 patients (1.7%) died within 90 days of COVID-19 diagnosis, with 0.4% among patients with a low ASCVD risk score, 1.5% among patients with an intermediate risk score, and 5.6% among patients with a high risk score. It presents the adjusted HR and 95% CI for the risk of hospitalization and mortality for the ASCVD risk score and risk score categories. The results indicate a 1.49 (95% CI 1.41 to 1.56) increased risk of hospitalization within 14 days of the COVID-19–positive test among patients with an intermediate risk and a 2.23 (95% CI 2.10 to 2.38) increased risk among patients with a high risk compared with patients at a low risk of developing ASCVD. The risk of mortality followed a similar trend, with a 1.77 (95% CI 1.76 to 1.79) increased risk among patients at an intermediate risk and 5.98 (95% CI 5.93 to 6.03) increased risk among patients at high risk. Figure 2 presents the unadjusted HR and 95% CI for the risk of hospitalization and mortality for individual components of the ASCVD risk score. The risk was significantly greater among Black patients (hospitalization HR 2.25, 95% CI 2.17 to 2.34; mortality: HR 1.85, 95% CI 1.65 to 2.07) and Hispanic/Latino patients (hospitalization: HR 1.90, 95% CI 1.83 to 1.99; mortality: HR 2.07, 95% CI 1.85 to 2.31) than White patients. Among the individual clinical components, the risk of hospitalization and mortality was greater among patients with a systolic blood pressure of ≥140 mm Hg than <140 mm Hg (hospitalization HR 1.56, 95% CI 1.51 to 1.62; mortality: HR 1.71, 95% CI 1.56 to 1.88), patients with diabetes (hospitalization HR 1.68, 95% CI 1.63 to 1.74; mortality: HR 2.13, 95% CI 1.95 to 2.33), smokers (hospitalization HR 1.33, 95% CI 1.28 to 1.37; mortality: HR 1.25, 95% CI 1.14 to 1.37), and those on blood pressure–lowering therapy (hospitalization HR 2.10, 95% CI 2.04 to 2.17; mortality: HR 4.12, 95% CI 3.74 to 4.54). The risk of hospitalization and mortality was smaller among patients with a high total cholesterol, defined as ≥200 mg/100 ml (hospitalization HR 0.75, 95% CI 0.73 to 0.78; mortality: HR 0.52, 95% CI 0.47 to 0.58) and a low HDL level, defined as <60 mg/100 ml (hospitalization HR 1.69, 95% CI 1.61 to 1.75; mortality: HR 1.79, 95% CI 1.61 to 2.0). This national study, using N3C data of a healthy patient population free of ASCVD events, indicates a clear dose-response relation between increasing 10-year ASCVD risk levels with a greater risk of COVID-19 complications. Previous studies indicate that patients with ASCVD and ASCVD risk factors, such as hypertension and diabetes, are at increased risk of COVID-19 complications.1Guan WJ Ni ZY Hu Y Liang WH Ou CQ He JX Liu L Shan H Lei CL Hui DSC Du B Li LJ Zeng G Yuen KY Chen RC Tang CL Wang T Chen PY Xiang J Li SY Wang JL Liang ZJ Peng YX Wei L Liu Y Hu YH Peng P Wang JM Liu JY Chen Z Li G Zheng ZJ Qiu SQ Luo J Ye CJ Zhu SY Zhong NS China Medical Treatment Expert Group for COVID-19Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (18830) Google Scholar,18Huang C Wang Y Li X Ren L Zhao J Hu Y Zhang L Fan G Xu J Gu X Cheng Z Yu T Xia J Wei Y Wu W Xie X Yin W Li H Liu M Xiao Y Gao H Guo L Xie J Wang G Jiang R Gao Z Jin Q Wang J Cao B Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (30119) Google Scholar, 19Wu Z McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention.JAMA. 2020; 323: 1239-1242Crossref PubMed Scopus (11620) Google Scholar, 20Wang D Hu B Hu C Zhu F Liu X Zhang J Wang B Xiang H Cheng Z Xiong Y Zhao Y Li Y Wang X Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (15048) Google Scholar We meaningfully add to the growing body of knowledge by focusing on patients with poor control of these risk factors, summarized by the intermediate and high risks of developing ASCVD using a large cohort of over 100,000 healthy patients. ASCVD risk factors, including uncontrolled hypertension, lipids, diabetes, and smoking, are highly prevalent in the United States,21Wall HK Ritchey MD Gillespie C Omura JD Jamal A George MG. Prevalence of key cardiovascular disease risk factors for million hearts 2022 - United States, 2011–2016. Vital Signs.MMWR Morb Mortal Wkly Rep. 2018; 67: 983-991Crossref PubMed Google Scholar and 1/4 of the population are at intermediate risk of developing ASCVD.6Vega GL Wang J Grundy SM. Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.J Clin Lipidol. 2022; 16: 66-74Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Our results confirm the public health messages of the importance of controlling ASCVD risk factors to maintain low scores not only to prevent future ASCVD but also COVID-19 complications. COVID-19 vaccination and booster efforts should target patients with intermediate and high scores of ASCVD risk scores, adding to the importance of using this score in clinical decision-making.22Lloyd-Jones DM Braun LT Ndumele CE Smith Jr, SC Sperling LS Virani SS Blumenthal RS Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the American Heart Association and American College of Cardiology.Circulation. 2019; 139: e1162-e1177Crossref PubMed Scopus (151) Google Scholar Data on whether patients with high ASCVD risk scores are more likely to receive the COVID-19 vaccine and boosters are not available but should be evaluated. In terms of the individual components of the score, our results indicate that older age is highly associated with worse COVID-19 outcomes, whereas being female is protective. The individual components of the score were also highly associated with COVID-19 severity, of which a history of diabetes and being on blood pressure–lowering therapy (as a proxy for hypertension diagnosis) resulted in the greatest risk of complications. The previous studies have reported on these associations; however, the cohorts tended to be smaller and mostly included older patients with established ASCVD. An important finding in our study is the clear racial and ethnic disparities in the risk of COVID-19 hospitalization and mortality, which confirms what is reported previously on the increased risk of complications and mortality among Black and Hispanic/Latino patients.23Arif YA Stefanko AM Garcia N Beshai DA Fan W Wong ND. Estimated atherosclerotic cardiovascular disease Risk: disparities and Severe COVID-19 Outcomes (from the National COVID Cohort Collaborative).Am J Cardiol. 2022; 183: 16-23Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 24Rossen LM Branum AM Ahmad FB Sutton P Anderson RN. Excess deaths associated with COVID-19, by age and race and ethnicity - United States, January 26–October 3, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1522-1527Crossref PubMed Google Scholar, 25Parpia AS Martinez I El-Sayed AM Wells CR Myers L Duncan J Collins J Fitzpatrick MC Galvani AP Pandey A. Racial disparities in COVID-19 mortality across Michigan, United States.EClinicalmedicine. 2021; 33100761Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Our results further add that this is the case even among healthy patients of color who are free of ASCVD. This is especially alarming because these patient groups have more prevalent ASCVD risk factors and worse control than their White counterparts.26Devareddy A Sarraju A Rodriguez F. Health disparities across the continuum of ASCVD risk.Curr Cardiol Rep. 2022; 24: 1129-1137Crossref PubMed Scopus (0) Google Scholar These findings partially explain the observed racial/ethnic disparities in COVID-19 outcomes and call for interventions targeting patients of color who continue to show worse ASCVD risk factor control. The observed increased risk of COVID-19 complications among patients at risk of ASCVD can be explained by a few mechanisms. Patients with a higher level of cardiovascular risk may have a lower grade of vascular inflammation, which combines with the immune response induced by the virus and leads to an aggravation of the inflammatory state.27Savoia C Schiffrin EL. Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions.Clin Sci (Lond). 2007; 112: 375-384Crossref PubMed Scopus (262) Google Scholar Furthermore, the procoagulant state reported in COVID-19 may increase the risk of thromboembolic and acute cardiovascular events by activating the prothrombotic factors in the atheromatous plaque.28Wang J Hajizadeh N Moore EE McIntyre RC Moore PK Veress LA Yaffe MB Moore HB Barrett CD. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series.J Thromb Haemost. 2020; 18: 1752-1755Abstract Full Text Full Text PDF PubMed Scopus (390) Google Scholar Finally, previous studies have reported a significant association between myocardial injury and fatal COVID-19 outcomes.29Ruan Q Yang K Wang W Jiang L Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.Intensive Care Med. 2020; 46: 846-848Crossref PubMed Scopus (3117) Google Scholar A few limitations were present in our study. First, a large proportion of patients in the cohort were missing components of the 10-year ASCVD risk score equation, specifically, systolic blood pressure, total cholesterol, and HDL values, and were excluded from the analysis. The excluded patients were younger but had a similar breakdown of gender and race/ethnicity. However, like other US cohorts, 1/4 of the patients in our cohort had an intermediate 10-year ASCVD risk, suggesting that our cohort is representative of the general US population.6Vega GL Wang J Grundy SM. Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.J Clin Lipidol. 2022; 16: 66-74Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Second, there are inherent limitations to the data collected from the EHR. Components of the ASCVD risk score were based on the most recent available data in the EHR, which may be outdated for some patients. Furthermore, patients may test for COVID-19 at an N3C participating site yet be hospitalized and/or die at another site that is not participating in N3C, with the potential of loss to follow-up. The mortality rate reported in our analysis is comparable with what is reported from the national US data for patients with COVID-19.30USAFacts. US COVID-19 cases and deaths by state. Available at: https://usafacts.org/visualizations/coronavirus-covid-19-spread-map. Accessed on December 19, 2022.Google Scholar Third, our analysis does not account for the effects of the COVID-19 vaccine; although, reports in previous studies suggest that patients with hypertension and other chronic conditions remain at an increased risk of COVID-19 complications even after receiving multiple doses of the vaccine.4Ebinger JE Driver M Joung S Tran T Barajas D Wu M Botting PG Navarrette J Sun N Cheng S. Hypertension and excess risk for Severe COVID-19 illness despite booster vaccination.Hypertension. 2022; 79: e132-e134Crossref Scopus (6) Google Scholar Fourth, we report a strong dose-response association between ASCVD risk and COVID-19 severity; however, our results are limited to associations and require further research before confirming the score's predictive ability for COVID-19 severity. In conclusion, we found a positive dose-response association between being at risk of developing ASCVD and COVID-19 complications, specifically, hospitalization and mortality. These findings extend the existing knowledge linking worse COVID-19 outcomes not only with established ASCVD but also among otherwise healthy patients at risk of developing events. COVID-19 vaccination and other preventive strategies should focus on patients with high ASCVD scores. The authors have no conflicts of interest to declare. The analyses described in this publication were conducted with the data and tools accessed through the NCATS N3C Data Enclave (https://covid.cd2h.org) and N3C Attribution & Publication Policy v 1.2-2020-08-25b supported by NCATS U24 TR002306 and Advocate Aurora Health's Small Research Grants. This research was possible because of the patients whose information is included within the data and the organizations (https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the ongoing development of this community resource [https://doi.org/10.1093/jamia/ocaa196]. Download .jpg (.26 MB) Help with files Supplementary Appendix 1: Map of patients by stateStates with 3 years after it was first declared.1 Full-Text PDF
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