Burden of illness among patients at high risk versus low risk for major cardiovascular events

Abstract

Objective:

This study was designed to compare the burden of illness (BOI) in patients at high risk versus low risk of developing a major cardiovascular (CV) event.

Methods:

This retrospective claims data analysis included commercial health plan members identified with a primary diagnosis on a medical claim for cardiovascular disease (CVD) from January 1, 2001 through December 31, 2002. Patients were categorized as: low risk (LR), high risk (HR), or high risk aged ≥55 (HR55), based on the ONTARGET clinical trial.

Results:

Most patients (85%) were in the LR category (8% in HR55, 7% in HR). A significantly greater proportion of patients in the HR55 group were hospitalized and experienced a greater number of ambulatory visits compared with LR and HR patients. Controlling for covariates, HR55 patients averaged $22,502 in paid healthcare services over 2 years versus $15,645 for HR patients and $11,423 for LR patients (p < 0.001). CV-related costs represented about 46% of costs for the HR55 group, versus 41% for the HR group and 31% for the LR group.

Limitations:

Claims data are collected for the purpose of payment and not research and the presence of a diagnosis code is not proof of disease, due to possible coding errors or the use of a rule-out criterion. Also, patients who died in the follow-up were not included in the analyses, resulting in lower BOI estimates. Finally, the results of this study reflect treatment of CVD in managed-care settings, and may not be applicable to a different type of population.

Conclusion:

This study demonstrates the high BOI associated with CVD, especially for patients within the high-risk group aged ≥55 years. Opportunities exist for reducing costs in this population.

Key words:

• burden of illness
• cardiovascular disease
• claims analysis
• cost
• risk

Introduction

Cardiovascular disease (CVD), including coronary artery disease (CAD), angina pectoris, myocardial infarction, congestive heart failure, hypertension, cardiomyopathy, arrhythmias, aortic stenosis, and aneurysm, affects an estimated 79.4 million American adults (37.1% of adults ≥20 years of age). One in three has one or more types of CVD. Of these, 37.5 million are estimated to be ≥65 years1. A sharp rise in the risk of a first cardiovascular (CV) event occurs in adults aged 45–60 years2. A recent study found that men aged ≥55 years had a threefold higher risk of CV events than their younger counterparts3. First major CV events occur in 7 per 1000 men per year at ages 35–44, 15 per 1000 at ages 45–54, 26 per 1000 at ages 55–64, 39 per 1000 at ages 65–74, 59 per 1000 at ages 75–84, and in 68 per 1000 at ages 85–94. For women, comparable rates occur 10 years later in life, although the gap narrows with advancing age4. CVD causes 1 of every 2.8 deaths in the US and remains the number one cause of death despite a 25% decline that has occurred in the past decade due to advances in treatment and prevention5.

CVD results in a significant burden to society. The estimated total (direct and indirect) cost of CVD for 2007 is $431.8 billion1. In 2001, $29.3 billion in payments were made to Medicare beneficiaries discharged from hospitals with a principal diagnosis of CVD – an average of $8,354 per discharge1. A more recent study based on medical claims data from a large US managed-care organization found total mean annual direct medical costs (2008US$) of almost $19,000 up to 7 years following a first CV event6, with almost half attributable to inpatient costs. They found the greatest differences in total annualized costs when comparing patients who experienced a secondary CVD-related hospitalization ($62,755) to those who did not ($13,509). A study of the 1987 National Medicaid Expenditure Survey and the 2000 Medical Expenditure Panel Survey, Household Component, showed the 15 most costly medical conditions and the estimated percentage increase in total healthcare spending for each condition from 1987 to 2000. Heart disease, at 8.06%, was ranked first as having the highest percentage impact on healthcare spending7. CVD-related operations and procedures are a major driver of costs. An estimated 6.4 million inpatient CVD-related operations and procedures were performed in the US in 2004; 3.2 million were performed on males, and 3.1 million on females8.

Accumulating experimental and epidemiological research indicates that activation of the renin–angiotensin–aldosterone system (RAAS), which results in elevated levels of angiotensin II hormone, has an important role in increasing the risk of CV events9–12. Angiotensin II hormone is a powerful vasoconstrictor, a potent blood pressure-increasing agent, and a promoter of both vascular and left ventricular hypertrophy13. These effects promote endothelial dysfunction, atherosclerosis, renal failure, and stroke. These data are consistent with the concept that the activated RAAS may also contribute to inflammatory processes within the vascular wall, and consequently to the development of acute coronary syndromes (ACS)14,15. Complete pharmacological blockade of RAAS is an appealing intervention for the prevention of CVD and is yet to be assessed in clinical outcomes studies16,17.

Angiotensin receptor blockers (ARBs) have the advantage of more complete blockade at the angiotensin II receptor, in contrast to angiotensin converting enzyme inhibitors (ACEIs), which inhibit the breakdown of angiotensinogen to angiotensin, but do not produce complete blockade of the RAAS. In addition, ARBs have been shown to suppress circulating levels of the inflammatory markers VCAM, TNF-α, and superoxide, which are implicated in atherogenesis18. Extensive evaluations have shown that ACEIs and ARBs can reduce mortality and morbidity in patients at high risk for CV events and in patients with controlled hypertension19–22. Currently, the American Heart Association/American College of Cardiology Guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease recommend that ACEIs be considered for all patients with CVD, but in particular, those with left ventricular ejection fraction <40% and in those with hypertension, diabetes, or chronic kidney disease, unless contraindicated22. The recently published Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint trial (ONTARGET) has shown that telmisartan (an ARB) has equivalent efficacy to ramipril (an ACEI) in the reduction of CVD in patients with vascular disease or high-risk diabetes23.

The primary purpose of this study was to assess and compare the burden of illness (BOI) in patients at high risk versus low risk of developing a major CVD event in a managed-care population. As defined by the ONTARGET trial, this analysis divided the sample population into three cohorts that included patients ≥55 years of age and at high risk for developing CVD, high-risk patients <55 years of age, and low-risk patients.

Patients and methods

Data source

This was a large retrospective claims database analysis using eligibility, pharmacy, and medical claims with linked race/ethnicity data from a US health plan offering commercial health benefits. The individuals covered by this health plan are geographically diverse across the US, with greatest representation in the South and Midwest. The plan provides fully insured coverage for physician, hospital, and prescription drug services, primarily in a preferred-provider arrangement. Approximately 20 million individuals included in the database with at least 1 month of enrollment during the period from January 1, 2001 through December 31, 2002 were considered for inclusion in the study. All data used for this analysis were de-identified and conformed to standards for the protection of private health information. All study data were de-identified and accessed with protocols compliant with the Health Insurance Portability and Accountability Act24.

Race was identified through a match carried out between the research database and a marketing database maintained for a large segment of the US population. Approximately 30% of the race data was collected directly from public records (e.g., driver’s license records), while the remaining data were assigned in accordance with a variety of algorithms and other data sources, such as census data.

Study sample

This study included commercial health plan members identified with a primary diagnosis on a medical claim for CVD (Table 1) from January 1, 2001 through December 31, 2002. The service date on the first-appearing qualifying claim was defined as the start of the 12-month baseline period. The subsequent 24-month period was defined as the follow-up period. Study patients had to be ≥18 years of age and commercially insured with pharmacy and medical benefits continuously for the 36 months inclusive of the baseline and follow-up periods.

Table 1.  Qualifying cardiovascular disease.

Cardiovascular disease	ICD-9 diagnosis codes, unless otherwise noted
Angina pectoris	413.xx
Myocardial infarction	410.xx, 412.xx
Hypertension	401.xx– 402, 405.xx
Ischemic heart disease	411.xx, 414.xx
Ischemic stroke	433.x1, 434.x1, 436.xx
Transient ischemic attack	435.xx
Multi-vessel percutaneous transluminal coronary angioplasty	Procedure codes: 00.66, 36.05 (ICD-9); 92981, 92984 (CPT)
Multi-vessel coronary artery bypass graft	Procedure codes: 36.10, 36.12–36.14 (ICD-9); 33534–33536, 33518–33523, 33511–33516 (CPT); S2206, S2209 (HCPCS)
Limb bypass surgery	Procedure codes: 39.25, 39.29 (ICD-9); 35510, 35512, 35516–35525, 35533, 35541–35558, 35565–35571, 35583–35587, 35616–35623, 35646–35661, 35665–35671, 35879–35881 (CPT)
Limb angioplasty	Procedure codes: 39.50 (ICD-9); 35456–35459, 35470, 35474–35475 (CPT)
Limb or foot amputation	Procedure codes: 84.0x–84.1x (ICD-9); 27590–27596, 27880–27888, 28800–28825 (CPT)
Diabetes with evidence of end organ damage defined as retinopathy, left ventricular hypertrophy, albuminuria	250.xx and one of the following: 250.5x, 362.0x, 362.1x, 429.3, 791.0, 593.6

Exclusion criteria were identified from the medical claims data during the baseline period, and patients were removed from the sample if these conditions were present. Patient selection criteria were based on the ONTARGET protocol23 (Table 2).

Table 2.  Exclusionary conditions.

Exclusionary condition	ICD-9 diagnosis codes, unless otherwise noted
Congestive heart failure	428.xx
Aortic and mitral valve stenosis	396.xx
Asymmetric septal hypertrophy	745.2; Procedure code: 33416 (CPT)
Malfunctioning prosthetic valve	996.02
Constrictive pericarditis	391.xx; 4230xx, 423.xx
Congenital heart disease	746.xx
Heart transplant	V42.1, 996.83; Procedure codes: 33.6, 37.5 (ICD-9); 33930–33945, 0051T (CPT)
Hemorrhagic stroke	430.xx
Renal disease	585.xx, 403.xx–404.xx; Procedure codes: 90918–90925, E1500–E1699, G0257, G0308–G0330 (CPT)
Primary aldosteronism	255.10
Hereditary fructose intolerance
Pregnancy/delivery	Procedure codes: 72.0–72.39, 72.5x–72.9, 73.22, 73.5x, 74.xx (ICD–9); 59400–59410, 59510–59515, 59610–59614, 59618–59622 (CPT)

All inclusion criteria, with the exception of hypertension and ischemic heart disease, were used to classify patients as being at high risk for CV events. Presence of any of these diagnoses or procedures in the 12-month baseline period resulted in a patient assignment into the high-risk cohort. High-risk patients ≥55 years of age (HR55) were considered separately from high-risk patients <55 years (HR). The low-risk category (LR) included patients of all ages who had no claims for any of the high-risk conditions. LR patients qualified for the study by having a diagnosis code for hypertension or for ischemic heart disease.

Variables

Demographics

Age and gender were determined from enrollment data for the study population. Age was calculated from birth year based on the index year. The Charlson Comorbidity Index score was calculated from claims data during the 12-month baseline period. The index diagnosis and qualifying high-risk conditions were also captured. Race/ethnicity was categorized as Caucasian, Black, Asian, Hispanic (Caucasian and non-Caucasian), and Other. For the multivariate analyses, patients with missing race data were classified as Other ethnicity.

Outcomes

Healthcare utilization measures were calculated for CVD-related services and all healthcare services in the 24-month follow-up period. CVD-related services were defined from claims with CVD diagnosis (ICD-9-CM diagnosis code 390.xx–459.xx) in the primary diagnosis position, including diseases such as hypertensive disease, ischemic heart disease, and diseases of pulmonary circulation. Measures were created separately for ambulatory services, emergency room services, and inpatient admissions. Medical, retail pharmacy, and total combined healthcare costs were computed from all claims and from CVD-related claims in the 24-month follow-up period. Pharmacy costs were attributed to CVD if the dispensing was for hypertension medication, coagulation and anticoagulation agents, antiarrhythmic agents, hemostatic agents, lipid-lowering agents, nitrates, vasodilators, vitamin K, cardiac glycosides, antiplatelets, and digoxin. Costs were calculated as the total amount paid by primary and secondary insurers and patients.

Analytic approach

All study variables including baseline and follow-up measures were analyzed descriptively, and results were stratified by risk group. Unadjusted comparisons between risk groups are presented. Relative risk of hospitalization in the 24-month follow-up period was modeled using logistic regression. Number of ambulatory visits was estimated using negative binomial regression. Costs were estimated using a generalized linear model with a gamma distribution and log link. Predicted mean costs for each risk group were produced. HR55 and HR were included as the primary predictors in the models, with LR as the reference group. Covariates in the models included Charlson Comorbidity Index score; male gender (female as reference); age 55–64, age 65+ (age <55 as reference); and Caucasian race (non-Caucasian as reference). The analysis was generated using SAS/STAT software, Version 8 of the SAS System for Unix25.

Results

Sample description

Over 1.3 million health plan members out of 16 million enrollees had a qualifying code on a medical claim in the calendar years of 2001 and 2002, and 326,887 were retained for analysis, having met all inclusion and exclusion criteria. Over 85.08% of the sample was defined as LR (n = 278,107), 6.97% as HR and <55 years of age (n = 22,775), and 7.96% as HR55 (n = 26,005). More than half of all subjects were male, with a larger proportion of males making up the HR55 group (59.61%) compared to HR (57.79%) and LR (52.37%) groups (p < 0.001). Mean age was 64 years among HR55 patients, 46 years for HR patients, and 52 years for LR patients (p < 0.001). Race data were missing for 25% of each risk-group population. Among those for whom race was reported, 88.60% of HR55 patients were Caucasian and 3.61% were Black, compared to 82.35% and 6.55% of HR patients, and 85.02% and 4.25% of LR patients, respectively. Significantly higher Charlson Comorbidity Index scores were associated with higher risk levels (0.47 LR; 1.26 HR; 1.72 HR55; p < 0.001).

Sample demographics can be seen in Table 3. Patients were stratified into the risk categories based on the presence of diagnoses and procedures during the 12-month baseline period. By definition, LR patients did not have any of these high-risk indicators. Among HR55 and HR patients, angina was the most common high-risk factor (38.16 vs. 45.58%; p < 0.001), followed by myocardial infarction, stroke, transient ischemic attack, and high-risk diabetes. Among LR patients, 92% qualified for study based on the diagnosis of hypertension, while the remainder of LR patients had a qualifying diagnosis of ischemic heart disease.

Table 3.  Demographics.

Demographic characteristic	HR55 (n = 26,005)	HR (n = 22,775)	LR (n = 278,107)
	n (%)	n (%)	n (%)
Age (years)
18–34	0 (0.00%)	1,665 (7.31%)	14,983 (5.39%)
35–44	0 (0.00%)	6,251 (27.45%)	49,036 (17.63%)
45–54	0 (0.00%)	14,859 (65.24%)	97,881 (35.20%)
55–64	16,396 (63.05%)	0 (0.00%)	83,203 (29.92%)
65+	9,609 (36.95%)	0 (0.00%)	33,004 (11.87%)
Gender
Female	10,504 (40.39%)	9,613 (42.21%)	131,918 (47.43%)
Male	15,501 (59.61%)	13,162 (57.79%)	146,189 (52.57%)
Race/ethnicity
Caucasian	17,224 (66.23%)	13,938 (61.20%)	176,548 (63.48%)
Black	1,170 (4.50%)	1,318 (5.79%)	17,773 (6.39%)
Hispanic	702 (2.70%)	1,108 (4.86%)	8,834 (3.18%)
Asian	189 (0.73%)	356 (1.56%)	2,873 (1.03%)
Other	155 (0.60%)	206 (0.90%)	1,638 (0.59%)
Missing	6,565 (25.25%)	5,849 (25.68%)	70,441 (25.33%)
High risk factor
Angina	9,924 (38.16%)	10,380 (45.58%)	0 (0.00%)
Myocardial infarction	6,581 (25.31%)	5,016 (22.02%)	0 (0.00%)
Ischemic stroke	5,052 (19.43%)	3,214 (14.11%)	0 (0.00%)
Transient ischemic attack	5,037 (19.37%)	3,726 (16.36%)	0 (0.00%)
High-risk diabetes	3,658 (14.07%)	2,862 (12.57%)	0 (0.00%)
Coronary artery bypass graft	1,088 (4.18%)	569 (2.50%)	0 (0.00%)
Angioplasty	639 (2.46%)	507 (2.23%)	0 (0.00%)
Limb angioplasty	441 (1.70%)	303 (1.33%)	0 (0.00%)
Limb/foot amputation	334 (1.28%)	314 (1.38%)	0 (0.00%)
Limb bypass	324 (1.25%)	171 (0.75%)	0 (0.00%)

Descriptive analysis

Almost all patients (99%) had evidence of ambulatory care in the 24-month follow-up period. CVD-related ambulatory visits were also prevalent, with 85.26% of HR55 patients, 66.41% of HR patients, and 79.03% of LR patients having at least one visit for ambulatory CVD-related services. More than a quarter of high-risk patients had an emergency room visit in the 24-month follow-up period, versus 25.80% of HR55 patients and 27.57% of HR patients (p < 0.010). Conversely, 20.78% of LR patients experienced an emergency room visit in the 24-month observation period (p < 0.001 versus both HR55 and HR). Only a small proportion of patients at each risk level had an emergency room visit for hypertension or a CVD-related diagnosis. A full 30.27% of HR55 patients had a hospitalization in the 2-year follow-up period, while 21.41% of HR patients and 14.88% of LR patients had at least one hospitalization (p < 0.001). Slightly more than 68% of HR55 patients with a hospitalization had a CVD-related hospitalization (54% of HR patients with a hospitalization and 46% of LR patients with a hospitalization). CVD-related hospitalizations occurred in 20.57% of the HR55 group versus 11.6% and 8.21% of the HR and LR groups, respectively (p < 0.001). On average, HR55 patients had 34 ambulatory visits and seven CVD-related ambulatory visits in 2 years, significantly higher than HR patients (28 visits overall and four CVD-related visits, p < 0.001), and LR patients (24 visits overall and four CVD-related visits, p < 0.001).

Unadjusted healthcare costs are shown in Table 4. HR55 patients had on average $20,796 in healthcare costs in the 2-year period. Approximately 75% of these costs were for medical services ($15,930), and the rest for retail pharmacy ($4,866). All mean costs for the HR55 patients were significantly higher than for HR and LR patients, who had $15,566 and $11,294 in mean total costs, respectively (p < 0.001). Costs were computed for CVD-related services. Mean CVD-related pharmacy costs were associated with risk level, with the HR55 group having mean CVD-related pharmacy costs of $1,774, significantly higher than HR patients ($1,087) and LR patients ($812). A similar pattern was observed for CVD-related medical costs, with mean costs of $7,402 for HR55 patients, $4,165 for HR patients, and $2,330 for LR patients.

Table 4.  Unadjusted healthcare utilization and costs.

Utilization/cost	HR55 (n = 26,005)	HR (n = 22,775)	LR (n = 278,107)
	n (%)	n (%)	n (%)
Ambulatory visits	25,750 (99.02%)	22,447 (98.56%)	274,335 (98.64%)
Emergency room visits	6,710 (25.80%)	6,279 (27.57%)	57,798 (20.78%)
Hospitalizations	7,872 (30.27%)	4,877 (21.41%)	41,370 (14.88%)
CVD-related ambulatory visits	22,172 (85.26%)	15,124 (66.41%)	220,528 (79.30%)
CVD-related emergency room visits	1,247 (4.80%)	827 (3.63%)	5,169 (1.86%)
CVD-related hospitalizations	5,375 (20.67%)	2,643 (11.60%)	18,824 (6.77%)
	Mean (SD)	Mean (SD)	Mean (SD)
Ambulatory visit count	34.32 (27.43)	28.28 (26.92)	24.29 (22.62)
CVD-related ambulatory visit count	6.75 (7.87)	3.95 (6.35)	3.68 (4.59)
Medical costs ($)	15,930 (30,132)	11,781 (26,663)	8,240 (19,501)
Pharmacy costs ($)	4,866 (4,915)	3,785 (5,455)	3,053 (4,119)
Total costs ($)	20,796 (31,420)	15,566 (28,511)	11,294 (20,771)
CVD-related medical costs ($)	7,402 (27,732)	4,165 (17,279)	2,330 (15,743)
CVD-related pharmacy costs ($)	1,774 (1,774)	1,087 (1,589)	812 (1,146)
CVD-related total costs ($)	9,176	5,252	3,142

Multivariate analysis

Adjusted healthcare utilization and cost ratios can be found in Table 5. Controlling for covariates, HR55 patients had a higher rate of ambulatory visits (incidence rate ratio [IRR]: 1.06; confidence interval [CI]: 1.04–1.07) and CVD-related ambulatory visits (IRR: 1.31; CI: 1.29–1.33) relative to LR patients, controlling for patient characteristics. HR patients had a significantly greater rate of ambulatory visits overall compared to LR patients (IRR: 1.11; CI:1.09–1.12) and a significantly greater rate of CVD-related ambulatory visits compared to LR patients (IRR: 1.18; CI:1.16–1.20). HR55 and HR patients were more likely than LR patients to experience hospitalizations overall and CVD-related hospitalizations. HR55 patients were 1.40 times more likely than LR patients to be hospitalized (CI: 1.35–1.44), and HR patients were 1.56 times more likely than LR patients to be hospitalized (CI: 1.50–1.61). The likelihood of a CVD-related hospitalization was even greater for HR55 patients in comparison to LR patients (odds ratio [OR]: 1.65; CI: 1.59–1.71) and HR patients (OR: 2.25; CI: 2.15–2.36). Ages 55–64 and 65+, Charlson Comorbidity Index score, and being Caucasian were all positively associated with all utilization outcomes, while being younger than 55 and being male were negatively associated with utilization.

Table 5.  Adjusted outcomes relative to low-risk patients.

Utilization/cost		Coefficient	Ratio	Robust SE	95% Lower CI	95% Upper CI	p-value
Ambulatory visits	High risk + 55	0.0578	1.0595	0.0072	1.0445	1.0746	0.000
	High risk	0.1030	1.1085	0.0074	1.0925	1.1247	0.000
CVD-related ambulatory visits	High risk + 55	0.2689	1.3085	0.0078	1.2887	1.3286	0.000
	High risk	0.1687	1.1837	0.0083	1.1647	1.2030	0.000
Inpatient stays	High risk + 55	0.3333	1.3955	0.0165	1.3511	1.4414	0.000
	High risk	0.4427	1.5570	0.0185	1.5016	1.6144	0.000
CVD-related inpatient stays	High risk + 55	0.5000	1.6487	0.0194	1.5872	1.7127	0.000
	High risk	0.8120	2.2525	0.0247	2.1462	2.3641	0.000
Total costs	High risk + 55	0.1058	1.1116	0.0071	1.0962	1.1273	0.000
	High risk	0.2335	1.2630	0.0073	1.2451	1.2813	0.000
Total CVD-related costs	High risk + 55	0.3789	1.4607	0.0074	1.4397	1.4820	0.000
	High risk	0.6889	1.9916	0.0082	1.9597	2.0240	0.000

Covariates used for the adjusted analysis included: HR55 and HR (LR as the reference group), Charlson Comorbidity Index score; male gender (female as reference); age 55–64, age 65+ (age <55 as reference); and Caucasian race (non-Caucasian as reference).

Consistent with the findings of the utilization analysis, patients in the HR55 and HR groups had significantly higher predicted mean costs, both overall and CVD-related, compared to the LR group. Over the 24-month follow-up period, predicted mean costs, controlling for age, gender, Charlson Comorbidity Index score, and race, were $22,502 for HR55 patients, $15,645 for HR patients, and $11,423 for LR patients. Predicted mean CV-related costs were $10,432 for HR55 patients, representing 46% of all costs for that group, compared to $6,490 for HR patients (41% of all costs), and $3,508 for LR patients (31% of all costs).

Discussion

The purpose of this study was to assess the BOI among patients with high-risk CVD. Although BOI studies on diseases within the CVD arena have been conducted, the authors are unaware of a more recent or comparably-sized BOI study of CVD in a managed-care setting. As such, it provides data on inpatient and outpatient resource utilization and cost.

Attention to CV risk factors to avoid serious events is discussed in the American Heart Association 2002 guideline for the primary prevention of CVD and stroke. The guideline provides treatment recommendations for smoking cessation, blood pressure control, aspirin use, blood lipid management, diabetes management, etc. which are fundamental to reduce clinically serious and costly first events26. Most patients with CVD were considered at low risk for a CV event based on the study criteria. The most common qualifying condition for these patients was hypertension, an important precursor to future comorbidity and mortality. Among patients at high risk for an event, ischemic heart disease was the most common qualifying diagnosis. These results are similar to the baseline characteristics reported in the ONTARGET study, which also showed the majority of enrolled patients had a history of CAD23.

The database in the present study contained 1.3 million patients with a qualifying diagnosis among 16 million health plan enrollees, suggesting a prevalence rate of roughly 12%. Assuming 15% of the health plan population with a CV diagnosis qualifies as high risk, 2.4 million enrollees may be at high risk for a CV event. This estimate is lower than the recently reported estimates of 37.1%1. However, this study is limited to commercial enrollees and does not represent the full spectrum of patients ≥65 years of age. The prevalence of high-risk patients <55 years of age (7%) was comparable to that cited in national reports (4% for females, 10% for males)1.

The present study confirmed national statistics indicating a high BOI for CVD, particularly in patients >65 years of age27. This study demonstrated that overall burden of CVD is high, and higher among high-risk patients compared to low-risk patients. With the high-risk patients stratified by age, older high-risk patients incur significantly more costs compared to younger (<55 years of age) high-risk patients. These findings were consistent across service type. Thirty percent of HR55 patients were hospitalized, a significantly greater proportion compared to HR patients (21%) and LR patients (15%). Over half of patients hospitalized experienced a CV-associated hospitalization. Over the 24-month follow-up period, HR55 patients experienced an average of 34 ambulatory visits, significantly greater than the HR patients (28 visits) and LR patients (24 visits). Controlling for patient characteristics, HR55 patients averaged $22,502 for 2 years, compared to $15,645 for HR patients and $11,423 for LR patients. Mean CV-related costs were $10,433, $6,490, and $3,508 for HR55, HR and LR patients, respectively. For HR55 patients, CV-related costs accounted for approximately half of all costs. These analyses show that CV-related costs are a significant driver of overall patient costs, particularly among those at higher risk and older age.

Several studies have estimated the costs of illness for CVD conditions such as CAD and ACS28–31. Russell et al estimated the cost of CAD based on a Markov model of the economic costs of CAD-related medical care28. First-year direct medical costs of treating CAD events were estimated to be $17,532 for fatal acute myocardial infarction (AMI) and $15,540 for nonfatal AMI. A more recent study by Etemad et al examined the burden and cost of illness of ACS in the managed-care population31. Total healthcare costs for the 13,731 patients evaluated were approximately $22,529 per patient for 1 year. Patients with a diagnosis of unstable angina appeared to have a lower mean index episode cost of $8,101, whereas AMI patients’ index cost was $14,254. A general link of disease severity to costs was seen in that study, as patients with unstable angina had somewhat lower index episode costs versus patients with AMI. These studies confirm the findings from the present study of an association between risk severity and high cost of illness for CVD.

Limitations

While claims data are extremely valuable for the efficient and effective examination of healthcare outcomes, treatment patterns, healthcare resource utilization and costs, claims data are collected for the purpose of payment and not research. Therefore, there are certain limitations associated with the use of claims data. Presence of a diagnosis code on a medical claim is not positive presence of disease, as the diagnosis may be incorrectly coded or included as a rule-out criterion rather than representing actual disease. Patients were included in this study based on diagnosis and procedure codes, and furthermore, were categorized into risk groups based on these diagnoses. While it is likely there are false positives in the sample, this error would typically suppress the costs by including lower-cost patients in the sample (i.e., patients screened for but not ultimately diagnosed with certain CV conditions).

Certain information is not readily available in claims data that could have an effect on study outcomes, such as certain clinical and disease-specific parameters. For example, while patients were assigned to risk categories based on presence of disease, blood pressure and other clinical parameters were not measurable in claims. These types of parameters would be somewhat predictive of severity and cost and may provide further detail in segmenting patients by risk strata.

The inclusion criteria, by default, excluded patients who died during the follow-up period. Patients who die typically incur very high costs in the last year of life. By excluding these patients from the present study, the estimate of the burden of CVD is lowered. In fact, the patients who died were analyzed separately to assess the BOI for them, and on a per-patient basis, their costs were substantially higher than those for the surviving sample. The unadjusted mean total cost of HR55 patients who died was $63,933. However, the patients included in the study represent those who may be the best candidates for intervention and treatment as they survived the entire analytic period. Further, the percentage of patients excluded due to death in the 2-year follow-up was approximately 1% of the full sample, which likely limits the impact of their high costs on the overall trend.

There are limitations to the ability to generalize the results of this study. The data used for this study come from a managed-care population (including commercially insured managed-care patients). Therefore, results of this analysis are primarily applicable to the treatment of CVD in managed-care settings, and may not be applicable to a Medicaid or other type of population. The plans used for analysis, however, are discounted fee-for-service, IPA-network plans, and not capitated or gate-keeper models. The plans used for analysis include a wide geographic distribution across the US, and therefore provide the capability for generalization to managed-care populations on a national level.

Conclusion

This study demonstrates the high BOI associated with CVD, especially for patients within the high-risk group aged ≥55 years. Patients who are older and have risk factors incur the highest costs. Given the rapidly aging US population, the CVD-related BOI could grow exponentially in the near future. The high percentage of patients hospitalized and the high rate of ambulatory care during the 2-year study period indicate that further opportunities exist for reducing costs in this population, perhaps by encouraging healthy lifestyle changes (e.g., smoking cessation, weight control). A recent study employing an Archimedes simulation model of CVD BOI based on National Health and Nutrition Education Survey (NHANES) data found that incidence of myocardial infarction in the US population could be reduced by up to 63% with prevention activities that included healthy lifestyle changes32. Although this study examined BOI in a US managed-care population, the broad geographic representation of the population should make the findings relevant for the greater US population.

Transparency

Declaration of funding:

This study was funded by Boehringer Ingelheim Pharmaceuticals, Inc.

Declaration of financial/other relationships:

C.H., V.Z., and F.C. have disclosed that they are employees of i3 Innovus, a company that received financial support from Boehringer Ingelheim Pharmaceuticals to conduct this study. S.D.S. and H.S. have disclosed that they are employees of Boehringer Ingelheim Pharmaceuticals, Inc.