Prediction of Cardiovascular Death in Racial/Ethnic Minorities Using Framingham Risk Factors

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1 Prediction of Cardiovascular Death in Racial/Ethnic Minorities Using Framingham s Laura P. Hurley, MD, MPH; L. Miriam Dickinson, PhD; Raymond O. Estacio, MD; John F. Steiner, MD, MPH; Edward P. Havranek, MD Background Risk factors for cardiovascular disease (CVD) derived from the Framingham study are widely used to guide preventive efforts. It remains unclear whether these risk factors predict CVD death in racial/ethnic minorities as well as they do in the predominately white Framingham cohorts. Methods and Results Using linked data from the National Health and Nutrition Examination Survey III (1988 to 1994) and the National Death Index, we developed Cox proportional hazard models that predicted time to cardiovascular death separately for non-hispanic white (NHW), non-hispanic black (NHB), and Mexican American (MA) participants ages 40 to 80 years with no previous CVD. We compared calibration and discrimination for the 3 racial/ethnic models. We also plotted predicted 10-year CVD mortality by age for the three racial/ethnic groups while holding other risk factors constant (3437 NHW, 1854 NHB, and 1834 MA subjects met inclusion criteria). Goodness-of-fit 2 tests demonstrated adequate calibration for the 3 models (NHW, P 0.49; NHB, P 0.47; MA; P 0.55), and areas under the receiver operating characteristic curves demonstrated similar discrimination (c-statistics: NHW, ; NHB, ; and MA, ). Older age was more strongly associated with CVD mortality in NHWs (hazard ratio, 3.37; 95% CI, 2.80 to 4.05) than NHBs (hazard ratio, 2.29; 95% CI, 1.91 to 2.75) and was intermediate in MAs (hazard ratio, 2.46; 95% CI, 1.95 to 3.11). Predicted 10-year mortality rate was highest for NHBs across all age ranges and was higher for MAs than NHWs until late in the seventh decade. Conclusions Framingham risk factors predict CVD mortality equally well in NHWs, NHBs, and MAs, but the strength of the association between individual risk factors and CVD mortality differs by race and ethnicity. When other risk factors are held constant, minority individuals are at higher risk of CVD mortality at younger ages than NHWs. (Circ Cardiovasc Qual Outcomes. 2010;3: ) Key Words: risk factors cardiovascular diseases prevention epidemiology Cardiovascular disease (CVD) is the leading cause of premature death in the United States, both in aggregate and subpopulations of whites, blacks, and Latinos. 1 Since 1950, mortality from cardiovascular disease has fallen steadily, 2 but the rate of decline has been greater in whites than in blacks. 3,4 Trends in cardiovascular mortality for Latinos have yet to be thoroughly assessed. In 2001, the proportion of premature deaths ( 65 years old) caused by heart disease was highest in blacks (31.5%) and was higher in Latinos (termed Hispanics) than whites (termed non-hispanic whites) (23.3% versus 14.4%). 5 In 2001, death rates for diseases of the heart and stroke were higher among blacks than whites. 6 Because more than half of the decline in mortality has been attributed to adequate treatment of risk factors, 7 one explanation for the racial and ethnic difference in trends in cardiovascular outcomes might be differences in prevalence and treatment of cardiovascular risk factors. The identification of the major independent risk factors for cardiovascular disease older age, male sex, smoking, diabetes, high total or low HDL cholesterol, and hypertension is largely a product of the Framingham Heart Study. 8,9 The usefulness of these risk factors has primarily been documented in whites. 8 Their value in other racial/ethnic groups may be affected by differences in prevalence and relative importance of these risk factors or by unidentified risk factors that are specific to nonwhites. CVD risk factors remain poorly defined in racial/ethnic minority populations. Although aggregated Framingham risk factors have been shown to underestimate risk in socioeconomically deprived populations in Britain 10 and to overestimate risk in Chinese 11 and Danish populations, 12 limited data are available regarding the ability of the Framingham risk factors to accurately predict cardiovascular disease in African Americans and Latinos. 13 Received October 24, 2008; accepted December 15, From the Divisions of General Internal Medicine (L.P.H., R.O.E.) and Cardiology (E.P.H.), Denver Health, Denver, Colo; the Department of Family Medicine (L.M.D.), University of Colorado Denver, Aurora, Colo; and the Institute for Health Research (J.F.S.), Kaiser Permanente Colorado, Denver, Colo. Guest Editor for this article was Sanjay Kaul, MD. The online-only Data Supplement is available at Correspondence to Laura P. Hurley, MD, Denver Health, 660 Bannock, MC 1914, Denver, CO laura.hurley@dhha.org 2010 American Heart Association, Inc. Circ Cardiovasc Qual Outcomes is available at DOI: /CIRCOUTCOMES

2 182 Circ Cardiovasc Qual Outcomes March 2010 This study was designed to assess the ability of Framingham risk factors to predict cardiovascular death in whites compared with Latinos and African Americans. NHANESIII n=33,944 WHAT IS KNOWN Few studies have evaluated how well individual cardiovascular risk factors predict cardiovascular mortality in racial/ethnic minorities. In fact, most studies looking at the association between risk factors and cardiovascular disease mortality have used the predominately white Framingham cohorts. WHAT THE STUDY ADDS Adults 40 and 80 n=9,910 n=9,538 n=8,546 Race/Ethnicity not recorded as Non-Hispanic white, Non=Hispanic black Or Mexican American, n= 372 Doctor ever told you you had a heart attack or stroke?=yes, n=992 Missing data, n=1,421 Looking at the National Health and Nutrition Examination Survey III, which oversampled non-hispanic blacks and Mexican Americans, we found that, in aggregate, cardiovascular risk factors predict cardiovascular disease mortality equally well in non- Hispanic whites, non-hispanic blacks, and Mexican Americans. However, individual risk factors had variable prevalences and associations with cardiovascular disease mortality in each racial/ethnic group. Most notably, age was more strongly associated with cardiovascular disease mortality in non-hispanic whites than in racial/ethnic minorities. Methods Data Sources The data sources for the study were the Third National Health and Nutrition Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. NHANES III is a cross-sectional survey conducted by the Centers for Disease Control and Prevention. During 1988 to 1994, a representative sample of the civilian noninstitutionalized US population was recruited into NHANES III using a multistage, stratified sampling design. 14 After an interview in the home, participants were invited to attend 1 of 3 examination sessions. NHANES III oversampled the elderly, non-hispanic blacks and Mexican Americans. A detailed description of the NHANES III survey and sampling procedures is available elsewhere. 14 The NHANES III Linked Mortality File contains the results of matching NHANES III subject identifiers with data available in the National Death Index as of December 31, Date of death and cause of death in the National Death Index are derived from death certificates. Study Population We studied subjects ages 40 to 80 years to closely resemble the age range in the study that validated the Framingham global CVD risk tool. 15 We excluded subjects who did not self-report being non-hispanic white (NHW), non-hispanic black (NHB), or Mexican American (MA). We excluded subjects with a previous myocardial infarction or stroke to eliminate the possible effect of treatment for prior CVD on the association between CVD risk factors and CVD mortality. Finally, we excluded subjects with missing risk factor data. n=7,125, Final Study Population Figure 1. Flow diagram of deriving study population. Definitions We chose as independent variables the risk factors identified in models developed by the Framingham study 15,16 : sex, age, smoking, diabetes, elevated total cholesterol, low concentrations of highdensity lipoprotein cholesterol (HDL), and systolic blood pressure (SBP) (treated or not). Smoking was defined as participants reporting that they were current smokers. Diabetes and antihypertensive use were defined by self-report. CVD mortality included death from coronary heart disease (CHD) or cerebrovascular disease and was defined by the principal cause of death on the death certificate listed as ICD9 codes to for deaths before or during 1999 or ICD-10 codes I10 15, I20 25, I50 51, I60 69, and I70 73 for deaths after We chose to investigate overall cardiovascular mortality rather than limit the study to CHD mortality. Overall cardiovascular mortality includes death from stroke, a particularly important end point in minority groups, especially NHBs. Statistical Analysis Descriptive statistics (mean, SD, proportion) were generated to describe the sample. 2 tests and 1-way ANOVA were used to compare subjects included in the analysis with those excluded because of missing data and to compare racial/ethnic groups on sociodemographic and clinical variables. Age, SBP treated, SBP untreated, total cholesterol, and HDL were treated as continuous variables. All continuous units were analyzed per 10 U of change (ie, 10 mm Hg for SBP). We also naturally logarithmically transformed continuous variables to see whether this improved discrimination and calibration of the models by minimizing the influence of extreme observations as in the Framingham model used as the basis for the current study. 15 To maximize predictive ability, we developed Cox proportional hazards models with days to death (up to 10 years) from CVD as the dependent variable and each potential risk factor as independent variables separately for NHWs, NHBs, and MAs. We checked the assumptions of the proportional hazards model for each variable and assessed for possible interactions between sex and the other risk factors. Subjects who did not complete a full 10-year period of observation or died of causes other than CVD were censored at the time of follow-up. To confirm differences in coefficients by race/ethnicity observed in separate analyses, we tested race/ethnicity by risk factor interactions in a stratified Cox proportional hazards model. Within each racial/ethnic group (NHWs, NHBs, and MAs), subjects were grouped into the following 5 risk categories: 25th percentile, 25 to 50th percentile, 51 to 75th percentile, 76 to 90th percentile, and 90th percentile. These percentile groupings were selected instead of using deciles to provide sufficient event rates in all categories. To assess calibration, Kaplan Meier survival curves within each racial/ethnic group were used to obtain 10-year mortality rates for each of the 5 strata. These were compared with predicted

3 Hurley et al Cardiovascular Death s in Minorities 183 Table 1. Cardiovascular s and Mortality by Sex and Race/Ethnicity, NHANES III NHW NHB MA Men Women Men Women Men Women (n 1457) (n 119) (n 1754) (n 105) (n 795) (n 68) (n 931) (n 60) (n 868) (n 51) (n 864) (n 49) Age, y* 58.6 (11.6) 71.3 (8.4) 59.3 (11.8) 72.2 (8.1) 55.3 (11.4) 65.2 (10.3) 54.4 (11.3) 66.1 (10.7) 55.4 (11.0) 64.8 (10.2) 55.0 (10.9) 67.5 (9.0) Untreated SBP, mm Hg* Treated SBP, mm Hg Total cholesterol mol/l (16.2) (18.4) (17.9) (19.2) (18.0) (28.5) (20.3) (21.2) (16.2) (27.6) (18.5) (21.8) (15.9) (20.0) (18.3) (21.8) (19.7) (18.9) (20.2) (19.4) (18.8) (31.4) (21.2) (26.3) (39.9) (40.2) (43.4) (48.1) (45.6) (42.6) (48.0) (40.5) (42.4) (42.5) (42.3) (46.4) HDL, mmol/l* 44.8 (13.2) 45.5 (14.4) 56.3 (16.2) 54.4 (20.2) 52.5 (18.2) 55.7 (19.8) 57.2 (18.5) 60.6 (18.0) 44.3 (12.3) 49.1 (22.1) 52.3 (14.2) 55.4 (19.9) Current smoker at baseline* With diabetes* Data are presented as mean (SD) or %. *P 0.01 for comparison by race/ethnicity for men using 2 or 1-way ANOVA. P 0.01 for comparison by race/ethnicity for women using 2 or 1-way ANOVA. P 0.05 for comparison by race/ethnicity for women using 2 or 1-way ANOVA. 19.5%, 24.1%, and 13.5% of NWH, NHB, and MA men, respectively, had treated SBP (P 0.01 for comparison by race/ethnicity using 2 ). 25.2%, 34.1%, and 17.6% of NWH, NHB, and MA women, respectively, had treated SBP (P 0.01 for comparison by race/ethnicity using 2 ). 5.5%, 3.4%, and 3.4% of NHW, NHB, and MA, respectively, had been prescribed a medication to lower cholesterol.

4 184 Circ Cardiovasc Qual Outcomes March 2010 Table 2. Hazard Ratios for 10-Year CVD Mortality for Individual CVD s for NHWs (n 3435) HR Univariable Coefficient Univariable HR Univariable Coefficient Female 0.32 ( 0.57, 0.07) 0.72 (0.56, 0.99) ( 0.73, 0.15) 0.68 (0.50, 0.92) 0.01 Age, per 10 y 1.26 (1.08, 1.44) 3.53 (2.97, 4.20) (1.03, 1.39) 3.37 (2.80, 4.05) Treated SBP, per 10 mm Hg 0.36 (0.28, 0.44) 1.44 (1.32, 1.56) (0.06, 0.26) 1.18 (1.08, 1.29) Untreated SBP, per 10 mg/dl 0.35 (0.27, 0.43) 1.42 (1.32, 1.53) (0.04, 0.20) 1.13 (1.04, 1.24) 0.01 Total cholesterol, per 10 mg/dl ( 0.04, 0.04) 1.00 (0.97, 1.03) ( 0.03, 0.03) (0.97, 1.03) 0.90 HDL cholesterol, per 10 mg/dl 0.06 ( 0.14, 0.02) 0.94 (0.86, 1.03) ( 0.10, 0.05) 0.98 (0.89, 1.07) 0.62 Smoking ( 0.34, 0.33) 1.00 (0.72, 1.38) (0.33, 0.99) 1.93 (1.39, 2.70) Diabetes 1.14 (0.79, 1.49) 3.14 (2.21, 4.45) (0.39, 1.09) 2.10 (1.47, 3.00) c-statistic from Cox model mortality for each racial/ethnic group by strata and a 2 goodnessof-fit statistic was calculated. For this test, larger probability values indicate a better fit. Additionally, predicted mortality was compared with observed mortality for the standard risk categories used in clinical practice: 10%, 10% to 20%, and 20% risk of 10-year CVD mortality. To assess discrimination, we calculated the c-statistic from the Cox regression models for each racial/ethnic group using methods described previously. 17,18 The c-statistic is equivalent to the probability that the predicted risk is higher for a case than a noncase and has a maximum value of Predicted 10-year CVD mortality by age for the 3 racial/ethnic groups was plotted, holding the other risk factors fixed at the mean levels of these risk factors for the entire cohort. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Inc, Cary, NC). Results Exclusions from the study population are presented in Figure 1. The final sample included 3437 NHW, 1854 NHB, and 1834 MA participants. Subjects included in the analysis were similar to subjects excluded in terms of HDL and SBP (P 0.05), but those excluded because of missing values were less likely to be male (43.4% versus 47.2%, P 0.01), older (61.1 years versus 57.7 years, P ), more likely to smoke (27.1% versus 24.2%, P 0.02), more likely to have diabetes (12.5% versus 10.5%, P 0.03), and had higher total cholesterol (230.1 versus 217.7, P 0.01). Racial/ethnic group risk factors and CVD mortality are presented in Table 1. Parameter estimates and hazard ratios from the Cox models for the 3 racial/ethnic groups are presented in Tables 2, 3, and 4. Table 3. Hazard Ratios for 10-Year CVD Mortality for Individual CVD s for NHBs (n 1854) Models using continuous variables per 10 U fit as well as models using log-transformed continuous variables and therefore are presented here for ease of interpretation. Models using logtransformed continuous variables are available in supplemental Tables 1 to 3. No significant sex interactions were found. Hazard ratios were generally of the expected magnitude and directions with 2 exceptions. First, the association between age and CVD mortality was stronger for NHWs (hazard ratio [HR], 3.37; 95% CI, 2.80 to 4.05) than for NHBs (HR, 2.29; 95% CI, 1.91 to 2.75) and MAs (HR, 2.46; 95% CI, 1.95 to 3.11). This was confirmed in the stratified Cox model that included a racial/ ethnic group by age interaction effect that was significant for NHBs compared with NHWs (P.001) and MAs compared with NHWs (P 0.03). Second, the associations between cholesterol (total and HDL) and CVD were notably weaker than expected. Stratified analysis revealed a significant racial/ethnic group by HDL interaction effect for MAs compared with NHWs (P 0.01). The calibration goodness-of-fit 2 statistics for CVD mortality for NHWs ( 2 [4 df] 3.44, P 0.49), NHBs 2 [4 df] 3.56 (P 0.47), and MAs ( 2 [4 df] 3.04, P 0.55) indicate adequate fit for all racial/ethnic groups when models are developed separately for each group (Figure 2A through 2C). Observed CVD mortality by commonly used risk categories is presented in Table 5. As observed in this table, stratification of risk using conventional American Heart Association/ American College of Cardiology risk categories were gener- Coefficient HR Univariable Coefficient Univariable HR Univariable Female 0.33 ( 0.68, 0.02) 0.72 (0.51, 1.01) ( 0.62, 0.12) 0.78 (0.54, 1.21) 0.18 Age, per 10 y 0.84 (0.68, 1.00) 2.32 (1.97, 2.74) (0.65, 1.01) 2.29 (1.91, 2.75) Treated SBP, per 10 mm Hg 0.15 (0.03, 0.27) 1.16 (1.04, 1.30) ( 0.09, 0.15) 1.03 (0.92, 1.16) 0.60 Untreated SBP, per 10 mm Hg 0.21 (0.13, 0.29) 1.23 (1.14, 1.34) ( 0.01, 0.18) 1.09 (0.99, 1.19) 0.08 Total cholesterol, per 10 mg/dl 0.01 ( 0.29, 0.05) 1.01 (0.97, 1.05) ( 0.06, 0.02) 0.98 (0.95, 1.02) 0.39 HDL cholesterol, per 10 mg/dl 0.08 (0.002, 0.16) 1.08 (0.99, 1.18) ( 0.05, 0.02) 1.04 (0.95, 1.14) 0.39 Smoking 0.09 ( 0.28, 0.46) 1.09 (0.76, 1.57) (0.16, 0.94) 1.73 (1.17, 2.54) 0.01 Diabetes 0.99 (0.58, 1.40) 2.69 (1.79, 4.05) (0.35, 1.19) 2.16 (1.42, 3.29) c-statistic from Cox model

5 Hurley et al Cardiovascular Death s in Minorities 185 Table 4. Hazard Ratios for 10-Year CVD Mortality for Individual CVD s for MAs (n 1832) Coefficient HR Univariable Coefficient Univariable HR (95% CI Univariable Female 0.06 ( 0.45, 0.33) 0.95 (0.64, 1.40) ( 0.16, 0.70) 0.77 (0.50, 1.17) 0.22 Age, per 10 y 1.01 (0.79, 1.23) 2.75 (2.22, 3.41) (0.66, 1.14) 2.46 (1.95, 3.11) Treated SBP, per 10 mm Hg 0.30 (0.20, 0.40) 1.36 (1.22, 1.51) (0.06, 0.30) 1.19 (1.06, 1.34) 0.01 Untreated SBP, per 10 mm Hg 0.27 (0.17, 0.37) 1.31 (1.19, 1.44) ( 0.02, 0.22) 1.10 (0.98, 1.24) 0.11 Total cholesterol, per 10 mg/dl 0.01 ( 0.03, 0.05) 1.01 (0.97, 1.06) ( 0.08, 0.04) 0.98 (0.94, 1.03) 0.52 HDL cholesterol, per 10 mg/dl 0.16 (0.04, 0.28) 1.18 (1.05, 1.34) (0.06, 0.30) 1.19 (1.06, 1.34) 0.01 Smoking 0.10 ( 0.37, 0.57) 1.11 (0.69, 1.76) ( 0.01, 0.97) 1.62 (0.99, 2.64) 0.05 Diabetes 1.14 (0.73, 1.55) 3.14 (2.08, 4.73) (0.29, 1.14) 2.05 (1.34, 3.14) 0.01 c-statistic from Cox model ally well calibrated; however, confidence intervals sometimes crossed the defined stratum boundaries. C-statistics summarizing the ability of racial/ethnic prediction functions to discriminate between subjects who had CVD death from those who did not were for NHWs, for MAs, and for NHBs. Predicted 10-year CVD mortality across age ranges are presented in Figure 3. Predicted mortality rate for NHBs is highest across all age ranges. Predicted mortality rate is higher for MAs than NHWs until late in the seventh decade. Discussion Principal Findings We assessed the ability of the well-known Framingham CVD risk factors (age, sex, SBP, cholesterol, smoking, and diabetes) to predict cardiovascular death separately in NHWs, NHBs, and MAs. Distinct racial/ethnic specific risk factor associations with CVD mortality were demonstrated; however, we found that survival models based on Framingham risk factors were well calibrated in all racial/ethnic groups when models were developed separately within each group. The discriminative capacity of our models was also similar for all 3 groups. Older age was more strongly associated with CVD mortality in NHWs than NHBs and MAs. With all other risk factors held constant, minority participants were at higher risk for cardiovascular death at younger ages compared with white participants. Previous Studies of Framingham Risk Functions in US Racial/Ethnic Minorities Our findings are similar to those of D Agostino et al. 13 This study compared calibration, recalibration, and discrimination of sex-specific Framingham risk models and risk models for CHD in specific racial/ethnic cohorts for black men and women in the Atherosclerosis Risk in Communities Study (1987 to 1988) and for Hispanic men in the Puerto Rico Heart Health Program (1965 to 1968). 13 They found that actual CHD event rates were similar to predicted event rates predicted event rates for blacks (men, 2 [8 df] 6.2, P 0.62; women, 2 [8 df] 5.0, P 0.76). The calibration for Puerto Rican men was poor ( 2 [8 df] 142, P.001); however, recalibration of this model using Puerto Rico Heart Program cohort mean values for risk factors and CHD incidence improved the performance of Framingham prediction functions ( 2 [8 df] 7.2, P 0.51). Discrimination of the models in this study (c-statistics 0.67 to 0.85) were comparable to our findings. Similarly, Liao et al, 20 pooling data from NHANES I and II (1976 to 1985), assessed CHD risk functions based on Framingham risk factors in whites and African Americans (termed blacks). Applying risk equations derived from white men to African American men overpredicted CHD mortality rate by 60%. Discrimination of CHD risk functions were similar to those found in our study and similar across race/sex groups (c-statistic for white men, 0.77; African American men, 0.76; white women, 0.84; and African American women, 0.82). These previous studies differed from the current study in that they were restricted to an evaluation of CHD; we investigated overall CVD mortality to capture the importance of stroke in minority populations. Also, the previous studies used cohorts initiated in years before that used in our study. Enrollment in the Puerto Rico Heart Health Program, Atherosclerosis Risk in Communities Study, and NHANES 1 and II occurred 1 to 2 decades before NHANES III enrollment (1988 to 1994) and before the widespread use of therapies such as reperfusion for acute myocardial information and effective cholesterol reduction with statins. Additionally, our study is based on a more recent interpretation of the Framingham risk function 15 in which SBP and total and HDL cholesterol are treated as continuous variables, blood pressure treatment is considered, and HDL is considered separately from total cholesterol. Previous Studies of Associations Between Cardiovascular s and CVD Mortality in Racial/Ethnic Minorities Few studies have evaluated the associations between risk factors and cardiovascular mortality by different racial/ethnic groups. In the study of D Agostino et al, 13 CHD mortality was associated with hypertension and elevated total cholesterol at varying levels and diabetes in white, black, and Puerto Rican men. CHD mortality was associated with hypertension for white and black women. Additionally, elevated total cholesterol, low HDL, diabetes, and current smoking were associated with CHD mortality for black women. There was no association with HDL cholesterol and CHD mortality in the black and Puerto Rican men studied, and there was no association with age in any of the women studied.

6 186 Circ Cardiovasc Qual Outcomes March 2010 Table 5. Estimated Versus Observed 10-Year CVD Mortality Using Clinically Relevant Framingham Risk Categories (Using 10-Unit Increments) Race/ Ethnicity Risk Category Total Sample, n of CVD, n of CVD, % NHW 10% (1.7, 2.9) 10% to 20% (9.6, 15.4) 20% (21.7, 30.5) MA 10% (2.1, 3.7) 10% to 20% (7.1, 15.7) 20% (18.9, 34.9) NHB 10% (2.8, 4.8) 10% to 20% (9.0, 16.6) 20% (16.1, 27.5) Figure 2. A, Predicted versus observed 10-year CVD mortality in NHW. 2 goodness-of-fit (4 df) 3.44, P B, Predicted versus observed 10-year CVD mortality in NHB. 2 goodnessof-fit (4 df) 3.56, P C, Predicted versus observed 10-year CVD mortality in MA. 2 goodness-of-fit (4 df) 3.04, P In the study of Liao et al, 20 there were no consistent differences in the associations between risk factors and CHD mortality across black and white groups studied except there were significant differences in coefficients for smoking status among men and for age among women. Most current understanding of the relationships between Framingham risk factors and CVD mortality in MAs stems from the San Antonio Heart Study. Wei et al 21 found that diabetes and hypertension were independently associated with CVD mortality, but current smoking and total cholesterol 240 mg/dl were not. None of these 4 variables were associated with CVD mortality in the non-hispanic white comparison group. In another San Antonio Heart Study, 22 age, sex, diabetes, hypertension (yes versus no), smoking, total cholesterol, and HDL were all significantly associated with CVD mortality. However, another study 23 of the same population showed only a trend for low HDL to predict CVD mortality in individuals without known CVD (HR, 1.46; 95% CI, 0.94 to 2.27). Potential Explanation for Current Findings We propose 2 potential explanations for the finding that minority individuals are at higher risk for CVD mortality at younger ages than NHWs. First, minority subjects may have received less effective care subsequent to baseline visits. Second, low socioeconomic position is common to US minorities, and low socioeconomic position has been suspected to be a risk factor for poor health 24 and has been shown to be a risk factor for cardiovascular disease, in particular in other populations. 10 Although the reasons underlying this association are not agreed on, environmental factors such as chronic emotional stress and poor diet have been suggested. With regard to the relationship between CVD mortality and total and HDL cholesterol, one potential explanation for the weakness of association between CVD mortality is that the inception of the NHANES III cohort coincided with the introduction of statin therapy. Widespread use of these agents during the follow-up period may have negated much of the impact of baseline hyperlipidemia on outcome. Individuals with nonfatal events may have been more likely to have their hyperlipidemia treated leading to lower death rates and weakening the relationship between lipids and CVD mortality. It is also possible that an Figure 3. Predicted mortality by racial/ethnic group across age ranges. *Other cardiovascular risk factors (age, sex, SBP, total cholesterol, HDL cholesterol, smoking, and diabetes) were held fixed at the mean levels of the entire cohort.

7 Hurley et al Cardiovascular Death s in Minorities 187 association between cholesterol levels and outcomes would have been statistically significant had our sample size, particularly in minority subjects, been larger; however, the relationships we found between cholesterol levels and CVD mortality were often in the opposite than expected direction, suggesting power was not the issue. Still, these findings are surprising and warrant further examination in contemporary cohorts. Strengths and Limitations To our knowledge, this is the first study to examine the use of the Framingham risk factors in a study that includes large numbers of all 3 major racial/ethnic groups in the United States using a national dataset. Our study had several limitations, however. Our definition of cardiovascular mortality relies on death certificate diagnoses, which are subject to error in the certification of the underlying causes of death. Because of the relatively few deaths in the racial/ethnic groups of interest, we were unable to perform sex-specific analyses. We did, however, account for sex as a separate risk factor. Also, we were not able to measure nonfatal events because end points were determined solely from the National Death Index. An analysis based on nonfatal CVD events would be an improvement on this study, but such data are currently unavailable. By excluding nonfatal events, we may have underestimated associations between risk factors and CVD. However, where a difference in predicted and observed outcomes has been found, it is similar in fatal and nonfatal events. 25 Last, we were unable to validate our models in different cohorts. Conclusions Taken in aggregate, Framingham risk factors predicted cardiovascular mortality in nationally representative samples of NHBs and MAs as well as they did in NHWs. Individually, however, the risk factors carried different strengths of association with CVD mortality, and prevalences of all risk factors differed across racial/ethnic groups. Holding other risk factors constant, estimated mortality from cardiovascular disease is higher for NHBs than NHWs across all age ranges and higher for MAs than NHWs until late in the seventh decade. The reasons for these differences deserve further investigation. Sources of Funding This work was supported by National Heart, Lung, and Blood Institute grant 5 U01 HL None. Disclosures References 1. Heart Disease Facts and Statistics. Available at: heartdisease/facts.htm. 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