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Cost-Effectiveness of Treating the Metabolic Syndrome Among the Uninsured
COSEHC Abstracts ESTROGEN ATTENUATES EARLY CAROTID ARTERY INJURY-INDUCED INFLAMMATION A.P. Miller, D. Xing, W. Feng, S. Oparil. Vascular Medicine and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States. Background: Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17B-estradiol, E2) inhibits neointima formation in animal models and the progestin medroxyprogesterone acetate (MPA) blocks this effect. Hypothesis: Perivascular inflammation as measured by leukocyte infiltration and expression of adhesion molecules/chemokines/ cytokines is modulated by exogenous estrogen administration in the balloon injury model of the rat carotid artery. Methods and Results: Ovariectomized (OVX) rats were randomly divided into subgroups and treated with E2, medroxyprogesterone acetate (MPA), E2⫹MPA, or vehicle (V) and subjected to balloon injury of the right carotid artery. After 24 hours, rats were euthanized and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry. Granulocytes and monocyte/macrophages were increased 26-fold and 12-fold, respectively, in injured compared to contralateral control arteries of vehicle treated rats. E2 reduced the granulocyte and monocyte/ macrophage populations of injured vessels by ⬃50% and increased T-lymphocytes, while MPA had no independent effect on inflammatory cells but completely blocked the E2 effect. Immunohistochemical examination verified these findings and localized inflammatory cells to the adventitial and periadventitial domains of injured vessels. To evaluate the early effects of estrogen on targets of inflammatory signaling, carotid arteries from both OVX⫹V and OVX⫹E2 rats were homogenized 2 hours after injury and RNA was isolated. Quantitative real-time RT-PCR revealed marked injury-induced mRNA expression upregulation of adhesion molecules (P-selectin, VCAM-1, ICAM-1), chemoattractants (MCP-1, CINC-2) and cytokines (IL-1, IL-6 and TNF-␣) with estrogenic attenuation of this injury effect. ELISA and protein array studies from homogenized OVX⫹V and OVX⫹E2 rat carotid arteries 6 hours after injury confirm upregulation of inflammatory mediators with estrogen blunting this injury-induced response. Conclusion: Estrogen attenuates neointimal formation after vascular injury, at least in part, by modulating pro-inflammatory mediator expression and by limiting leukocyte entry from adventitial tissues into injured vessels early in the injury response. INCREASING MORTALITY IS ASSOCIATED WITH HIGH SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE AND LOW SYSTOLIC BLOOD PRESSURE IN NORMOTENSIVE PATIENTS ON MAINTENANCE HEMODIALYSIS. D. Banerjee1, B.A. Walters2, A. Banerjee1, P. Pennell1. 1 Division of Nephrology and Hypertension, University of Miami, Miami, FL. 2Outcomes Research, Gambro Healthcare, Ft. Lauderdale, FL. The relationship of hypertension to all-cause mortality was evaluated in 33,636 patients on hemodialysis (HD) for 16 months (systolic blood pressure (SBP) 153 ⫹/- 21 mm Hg, pulse pressure 71 ⫹/- 17mm Hg). Hypertension (SBP140 or DBP90) was present in 74% of the entire population. Hypertensive patients had a predominance of systolic hypertension (SHT) (98.8%) and isolated systolic hypertension (ISHT) (68%). Among hypertensive patients, mortality was higher in patients with ISHT and SHT than in patients with diastolic hypertension (DHT), isolated diastolic hypertension (IDHT) and combined systolic and diastolic hypertension. (Table 1) Patients with “normal BP” were classified into four groups, demonstrating increasing mortality with decreasing SBP. (Table 2)
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The data demonstrate that hypertension in HD patients is predominantly systolic and that elevated SBP is a much stronger predictor of mortality than DBP in hypertensive HD patients. Mortality in non-hypertensive HD patients is highly correlated with deteriorating SBP and is probably related to advancing cardiomyopathy. We conclude that systolic hypertension is a strong predictor of mortality in HD patients without cardiomyopathy, who have poor control of BP. Table 1: MORTALITY IN 24,907 HYPERTENSIVE PATIENTS GROUPS
NUMBER
BP (MEAN)
%MORTALITY
ISHT SHT IDHT DHT COMBINED
16591 24605 302 8295 7993
158/78 162/85 135/93 168/98 170/99
20.3* 18.0* 13.9# 13.5* 13.6*
ISHT ⫽ SBP ⬎140 ⫹ DBP⬍90, SHT ⫽ SBP⬍140, IDHT ⫽ SBP⬎140 ⫹ DBP⬍90, DHT ⫽ DBP⬎90, COMBINED ⫽ SBP⬎140 ⫹ DBP⬎90; *p⬍0.00001 and # p⬍0.01 compared to ISHT Table 2: MORTALITY IN 8729 “NORMOTENSIVE” PATIENTS SBP (mm Hg)
% MORTALITY
130–140 120–130 110–120 ⬍110
21.7 27.0* 34.0* 43.7*
*p ⬍0.001 compared to previous rows COST-EFFECTIVENESS OF TREATING THE METABOLIC SYNDROME AMONG THE UNINSURED D. Bangalor, J. McAlearney, R. Schuster. Wright State University Health Systems Management, Kettering, OH. Context: The Metabolic Syndrome (MS) is becoming increasingly common among US adults; 23.7% of the US population has MS. Obesity, hyperlipidemia, glucose intolerance or NIDDM, and hypertension are the main components of MS leading to higher risk of cardiovascular events for patients with MS, The uninsured are seldom identified and treated, and consequently rely on emergency department visits for treatment of events related to MS. This results in an expensive treatment that is borne by the society. Montgomery County in Ohio has a larger population of the uninsured (15%) compared to the state (11.2%) and national averages (14%) and an estimated 88% of the uninsured with MS in Montgomery County are aged between 40 and 64. Objective: To estimate the cost-effectiveness of treating the risk factors of the metabolic syndrome among the uninsured. Population: Uninsured with MS between the ages of 20 and 64. Design: The number of uninsured adults with the metabolic syndrome in Montgomery County is estimated to be 6,510. The value to the society in treating the risk factors rather than the events is determined by estimating the cost for the treatment and the effectiveness as a result of the treatment. Three health states are chosen as primary end points (stroke, myocardial infarction, and and-stage renal disease) to model the progression of MS. All costs, outcomes and probabilities of events are derived from medical literature, clinical trials, and population based studies. Costs include that of medication, doctor visits, tests, and hospitalization. Effectiveness is measured in terms of Quality Adjusted Life Years (QALY). Both cost and QALY are discounted at 3% annual rate. May 2004 Volume 327 Number 5
Methodology: Markov model is used to determine the progression of MS and to estimate the cost-effectiveness of this study. Treating risk factors at the onset lowers the incidence of primary end points. The cost of treating patients for their risk factors and the improvement in their quality of life is compared with the cost and effectiveness of treating an event occurring if a patient is untreated. Outcome Measure: Cost per QALY is used as a primary outcome of the study. Results: The cost-effectiveness ratio for intense treatment of the risk factors is $1,670.29 per QALY. The treatment of events alone resulted in $1.808.04 per QALY. The incremental cost- effectiveness ratio in favor of treating events alone was $6.407.73 per QALY gained. A sensitivity analysis performed for increasing age showed that it was more cost-effective to treat patients between the ages 40 and 64. Conclusion: Based on the results of the analysis, treating risk factors improves health outcomes at a very low cost-effectiveness ratio. Although treating events alone appeared to have higher QALY at a moderately higher cost, we argue that the effect of treatment causes patients to live longer, the effect of which is not captured in the model.
high blood pressure despite correction of the arterial anomaly. This cross-sectional study investigated the difference in pulse pressure and arterial compliance of persons who underwent COA repair during and beyond the second decade of life. The data consisted of twenty-four patients with ages ranged from 18 to 58. Three groups of patients were studied; one consisted of persons with an unrepaired COA, while the other two had the COA repaired either before age 20 or after age 20. The mean pulse pressures were 54, 70, and 85 mmHg for COA repaired before age 20 years, COA repaired after age 20 years, and unrepaired COA, respectively. The mean arterial compliances were 1.7, 1.0, and 0.8 mL/mmHg for COA repaired before age 20 years, COA repaired after 20 years, and unrepaired COA, respectively. Figures 1 and 2 highlight the results. The results indicate that both blood pressure and pulse pressure are lower the earlier COA repair is performed. Furthermore, the improvement in arterial compliance was greater when repair of COA occurred earlier in life. Persons with an unrepaired COA had the worst compliance. While this study does not offer any changes in the current management of COA, it does provide insight into the role that arterial compliance may play in sustaining hypertension post-COA repair.
DELAYED REPAIR OF COARCTATION OF THE AORTA NEGATIVELY IMPACTS ARTERIAL COMPLIANCE C.E. Tabe, J. Kwagyan, O.S. Randall. Department of Medicine, Howard University, Washington, DC. Coarctation of the aorta (COA) is a medical condition that has been classified as a surgically correctable cause of hypertension (HTN). The incidence of persistent HTN after COA repair is higher in persons whose operation is delayed until adulthood. We hypothesize arterial compliance changes to be responsible for the perturbation of
MONITORING GLOBAL RISK OF CARDIOVASCULAR MORBIDITY IN AN EMERGENCY DEPARTMENTBASED HYPERTENSION REGISTRY D. Cline. Division of Emergency Medicine, Wake Forest University School of Medicine, Winston-Salem NC Background: Emergency Departments see a unique population of patients who, for a variety of reasons including socio-economic status and access to health care, may be at greater risk for cardiovascular morbidity than the general population. Data from the National Ambulatory Medical Care Survey demonstrates that Emergency Departments (ED) are being used increasingly as a primary source of health care for patients. Objective: To assess the global risk of cardiovascular morbidity in patients seen in a busy community-based ED utilizing a newly established Hypertension Registry. Setting: A university hospital with 65,000 annual emergency patient visits; 44 percent of patients are minorities. Methods: All patients presenting to the emergency department age18 years or older are screened for hypertension in addition to race, sex, and history of cardiovascular disease. The charts of all patients with blood pressure over 130/85 mm Hg or a history of hypertension (including medications) are assessed for the concomitant presence of cardiovascular risk factors including diabetes, smoking, hypercholesterolemia, and prior complications of hypertension including stroke, congestive heart failure, and coronary artery disease. Home medications are recorded. ED course variables include cardiovascular medications given, subsequent blood pressures, diagnoses, admission status, discharge diagnosis and counseling. Results: 3,923 patients were screened over 60 days. Twenty-nine percent gave a history of hypertension, and 37.4% had a blood pressure meeting at least stage 1 criteria (⬎ 140/90 mm Hg). The majority of patients meeting Stage 1 criteria were unaware of their hypertension (52.7%). The table shows the increased frequency of both co-morbidities and prior complications of hypertension with advancing stages of hypertension in ED patients. The frequency of hypercholesterolemia did not vary with hypertension. Conclusions: In this assessment of emergency department patients, global risk factors for cardiovascular morbidity increase with increasing stage of hypertension, and the frequency of known complications increase with the level of blood pressure. These risk factors are found in higher frequency than national averages. Reflecting the national changes in health care utilization, ED based hypertension registries may provide more timely and accurate information on cardiovascular risk and complications in community populations.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
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The data demonstrate that hypertension in HD patients is predominantly systolic and that elevated SBP is a much stronger predictor of mortality than DBP in hypertensive HD patients. Mortality in non-hypertensive HD patients is highly correlated with deteriorating SBP and is probably related to advancing cardiomyopathy. We conclude that systolic hypertension is a strong predictor of mortality in HD patients without cardiomyopathy, who have poor control of BP. Table 1: MORTALITY IN 24,907 HYPERTENSIVE PATIENTS GROUPS
NUMBER
BP (MEAN)
%MORTALITY
ISHT SHT IDHT DHT COMBINED
16591 24605 302 8295 7993
158/78 162/85 135/93 168/98 170/99
20.3* 18.0* 13.9# 13.5* 13.6*
ISHT ⫽ SBP ⬎140 ⫹ DBP⬍90, SHT ⫽ SBP⬍140, IDHT ⫽ SBP⬎140 ⫹ DBP⬍90, DHT ⫽ DBP⬎90, COMBINED ⫽ SBP⬎140 ⫹ DBP⬎90; *p⬍0.00001 and # p⬍0.01 compared to ISHT Table 2: MORTALITY IN 8729 “NORMOTENSIVE” PATIENTS SBP (mm Hg)
% MORTALITY
130–140 120–130 110–120 ⬍110
21.7 27.0* 34.0* 43.7*
*p ⬍0.001 compared to previous rows COST-EFFECTIVENESS OF TREATING THE METABOLIC SYNDROME AMONG THE UNINSURED D. Bangalor, J. McAlearney, R. Schuster. Wright State University Health Systems Management, Kettering, OH. Context: The Metabolic Syndrome (MS) is becoming increasingly common among US adults; 23.7% of the US population has MS. Obesity, hyperlipidemia, glucose intolerance or NIDDM, and hypertension are the main components of MS leading to higher risk of cardiovascular events for patients with MS, The uninsured are seldom identified and treated, and consequently rely on emergency department visits for treatment of events related to MS. This results in an expensive treatment that is borne by the society. Montgomery County in Ohio has a larger population of the uninsured (15%) compared to the state (11.2%) and national averages (14%) and an estimated 88% of the uninsured with MS in Montgomery County are aged between 40 and 64. Objective: To estimate the cost-effectiveness of treating the risk factors of the metabolic syndrome among the uninsured. Population: Uninsured with MS between the ages of 20 and 64. Design: The number of uninsured adults with the metabolic syndrome in Montgomery County is estimated to be 6,510. The value to the society in treating the risk factors rather than the events is determined by estimating the cost for the treatment and the effectiveness as a result of the treatment. Three health states are chosen as primary end points (stroke, myocardial infarction, and and-stage renal disease) to model the progression of MS. All costs, outcomes and probabilities of events are derived from medical literature, clinical trials, and population based studies. Costs include that of medication, doctor visits, tests, and hospitalization. Effectiveness is measured in terms of Quality Adjusted Life Years (QALY). Both cost and QALY are discounted at 3% annual rate. May 2004 Volume 327 Number 5
Methodology: Markov model is used to determine the progression of MS and to estimate the cost-effectiveness of this study. Treating risk factors at the onset lowers the incidence of primary end points. The cost of treating patients for their risk factors and the improvement in their quality of life is compared with the cost and effectiveness of treating an event occurring if a patient is untreated. Outcome Measure: Cost per QALY is used as a primary outcome of the study. Results: The cost-effectiveness ratio for intense treatment of the risk factors is $1,670.29 per QALY. The treatment of events alone resulted in $1.808.04 per QALY. The incremental cost- effectiveness ratio in favor of treating events alone was $6.407.73 per QALY gained. A sensitivity analysis performed for increasing age showed that it was more cost-effective to treat patients between the ages 40 and 64. Conclusion: Based on the results of the analysis, treating risk factors improves health outcomes at a very low cost-effectiveness ratio. Although treating events alone appeared to have higher QALY at a moderately higher cost, we argue that the effect of treatment causes patients to live longer, the effect of which is not captured in the model.
high blood pressure despite correction of the arterial anomaly. This cross-sectional study investigated the difference in pulse pressure and arterial compliance of persons who underwent COA repair during and beyond the second decade of life. The data consisted of twenty-four patients with ages ranged from 18 to 58. Three groups of patients were studied; one consisted of persons with an unrepaired COA, while the other two had the COA repaired either before age 20 or after age 20. The mean pulse pressures were 54, 70, and 85 mmHg for COA repaired before age 20 years, COA repaired after age 20 years, and unrepaired COA, respectively. The mean arterial compliances were 1.7, 1.0, and 0.8 mL/mmHg for COA repaired before age 20 years, COA repaired after 20 years, and unrepaired COA, respectively. Figures 1 and 2 highlight the results. The results indicate that both blood pressure and pulse pressure are lower the earlier COA repair is performed. Furthermore, the improvement in arterial compliance was greater when repair of COA occurred earlier in life. Persons with an unrepaired COA had the worst compliance. While this study does not offer any changes in the current management of COA, it does provide insight into the role that arterial compliance may play in sustaining hypertension post-COA repair.
DELAYED REPAIR OF COARCTATION OF THE AORTA NEGATIVELY IMPACTS ARTERIAL COMPLIANCE C.E. Tabe, J. Kwagyan, O.S. Randall. Department of Medicine, Howard University, Washington, DC. Coarctation of the aorta (COA) is a medical condition that has been classified as a surgically correctable cause of hypertension (HTN). The incidence of persistent HTN after COA repair is higher in persons whose operation is delayed until adulthood. We hypothesize arterial compliance changes to be responsible for the perturbation of
MONITORING GLOBAL RISK OF CARDIOVASCULAR MORBIDITY IN AN EMERGENCY DEPARTMENTBASED HYPERTENSION REGISTRY D. Cline. Division of Emergency Medicine, Wake Forest University School of Medicine, Winston-Salem NC Background: Emergency Departments see a unique population of patients who, for a variety of reasons including socio-economic status and access to health care, may be at greater risk for cardiovascular morbidity than the general population. Data from the National Ambulatory Medical Care Survey demonstrates that Emergency Departments (ED) are being used increasingly as a primary source of health care for patients. Objective: To assess the global risk of cardiovascular morbidity in patients seen in a busy community-based ED utilizing a newly established Hypertension Registry. Setting: A university hospital with 65,000 annual emergency patient visits; 44 percent of patients are minorities. Methods: All patients presenting to the emergency department age18 years or older are screened for hypertension in addition to race, sex, and history of cardiovascular disease. The charts of all patients with blood pressure over 130/85 mm Hg or a history of hypertension (including medications) are assessed for the concomitant presence of cardiovascular risk factors including diabetes, smoking, hypercholesterolemia, and prior complications of hypertension including stroke, congestive heart failure, and coronary artery disease. Home medications are recorded. ED course variables include cardiovascular medications given, subsequent blood pressures, diagnoses, admission status, discharge diagnosis and counseling. Results: 3,923 patients were screened over 60 days. Twenty-nine percent gave a history of hypertension, and 37.4% had a blood pressure meeting at least stage 1 criteria (⬎ 140/90 mm Hg). The majority of patients meeting Stage 1 criteria were unaware of their hypertension (52.7%). The table shows the increased frequency of both co-morbidities and prior complications of hypertension with advancing stages of hypertension in ED patients. The frequency of hypercholesterolemia did not vary with hypertension. Conclusions: In this assessment of emergency department patients, global risk factors for cardiovascular morbidity increase with increasing stage of hypertension, and the frequency of known complications increase with the level of blood pressure. These risk factors are found in higher frequency than national averages. Reflecting the national changes in health care utilization, ED based hypertension registries may provide more timely and accurate information on cardiovascular risk and complications in community populations.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
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