Multimorbidity in Atherosclerotic Cardiovascular Disease and Its Associations With Adverse Cardiovascular Events and Healthcare Costs: A Real-World Evidence Study

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality and disability in the United States and worldwide. Objective: To assess the multimorbidity burden and its associations with adverse cardiovascular events (ACE) and healthcare costs among patients with ASCVD. Methods: This is a retrospective observational cohort study using Aetna claims database. Patients with ASCVD were identified during the study period (1/1/2018-10/31/2021). The earliest ASCVD diagnosis date was identified as the index date. Qualified patients were ≥18 years of age and had ≥12 months of health plan enrollment before and after the index date. Comorbid conditions were assessed using all data available within 12 months prior to and including the index date. Association rule mining was applied to identify comorbid condition combinations. ACEs and healthcare costs were assessed using all data within 12 months after the index date. Multivariable generalized linear models were performed to examine the associations between multimorbidity and ACEs and healthcare costs. Results: Of 223 923 patients with ASCVD (mean [SD] age, 73.6 [10.7] years; 42.2% female), 98.5% had ≥2, and 80.2% had ≥5 comorbid conditions. The most common comorbid condition dyad was hypertension-hyperlipidemia (78.7%). The most common triad was hypertension-hyperlipidemia-pain disorders (61.1%). The most common quartet was hypertension-hyperlipidemia-pain disorders-diabetes (30.2%). The most common quintet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity (16%). The most common sextet was hypertension-hyperlipidemia-pain disorders-diabetes-obesity-osteoarthritis (7.6%). The mean [SD] number of comorbid conditions was 7.1 [3.2]. The multimorbidity burden tended to increase in older age groups and was comparatively higher in females and in those with higher social vulnerability. The increased number of comorbid conditions was significantly associated with increased ACEs and increased healthcare costs. Discussion: Extremely prevalent multimorbidity should be considered in the context of clinical decision-making to optimize secondary prevention of ASCVD. Conclusions: Multimorbidity was extremely prevalent among patients with ASCVD. Multimorbidity patterns varied considerably across ASCVD patients and by age, gender, and social vulnerability status. Multimorbidity was strongly associated with ACEs and healthcare costs.

Keywords: adverse cardiovascular events; atherosclerotic cardiovascular disease; comorbidity; healthcare costs; multimorbidity; real-world evidence; secondary prevention.

Figure 1.. Proportion of ASCVD Patients With the Indicated Number of Comorbid Conditions and Summed Proportions of Multimorbidity With the Indicated Number of Comorbid Conditions

(A) Proportion of ASCVD patients with the indicated number of comorbid conditions by age group. (B) Summed proportions of multimorbidity with the indicated number of comorbid conditions by age group. (C) Proportion of ASCVD patients with the indicated number of comorbid conditions by gender. (D) Summed proportions of multimorbidity with the indicated number of comorbid conditions by age and gender. Abbreviation: ASCVD, atherosclerotic cardiovascular disease.

Figure 2.. Prevalence of Adverse Cardiovascular Events (ACEs) by Number of Comorbid Conditions Group (A) and Adjusted Odds Ratio of Comorbid Conditions Group for ACEs (B)

(A) Bar chart of prevalence of ACEs during the 12-month follow-up period by number of comorbid conditions group among patients with ASCVD. (B) Forest plot of multivariable adjusted odds ratios (AOR) of number of comorbid conditions group for ACEs. Adjusted variables included age, gender, geographic region, rural or urban residence, household income, Social Vulnerability Index, and type of health insurance. The vertical dashed blue line represents an AOR of 1 as the reference line, which is associated with equal odds for all number of comorbid conditions groups. For each AOR displayed, the orange circle symbol depicts the AOR, and the horizontal blue line represents the 95% CI. Lines that do not cross the reference line are statistically significant. Abbreviations: ACEs, adverse cardiovascular events; ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; MACE, major adverse cardiovascular events.

Figure 3.. Total All-cause Healthcare Cost by Number of Comorbid Conditions Group (A) and Adjusted Cost Ratio of Comorbid Conditions Group (B)

(A) Bar chart of total healthcare cost per patient per year by number of comorbid conditions group among patients with ASCVD. (B) Forest plot of multivariable adjusted cost ratios (ACR) of number of comorbid conditions group for total all-cause healthcare cost. Adjusted variables included age, gender, geographic region, rural or urban residence, household income, social vulnerability index, and type of health insurance. The vertical dashed blue line represents a ACR of 1 as the reference line, which is associated with equal costs for all number of comorbid conditions groups. For each ACR displayed, the orange circle symbol depicts the ACR, and the horizontal blue line represents the 95% CI. Lines that do not cross the reference line are statistically significant.