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METHODS

Routine follow-up of the cohort for ascertainment of self-reported non-fatal events has not occurred. However, morbidity data are available from Medicare fee-for-service claims data obtained from the Centers for Medicare and Medicaid Services for surviving participants who were 65 years or older and thus eligible for Medicare benefits during the period from 1984, the first year Medicare data were available for public use, through 2002. Medicare data for each participant were cross-referenced by Social Security number, sex, name, and birth date. Records include (for each medical service billed to Medicare) date of service, primary discharge diagnosis, and up to 9 other diagnoses coded according to the International Classification of

Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).1,2 Hospitalizations for stroke, myocardial infarction, or heart failure, the main morbidity outcome measures for this study, were defined as any primary discharge diagnosis with ICD-9-CM codes 430 - 438, 410, or 428 respectively, in inpatient claims from 1984-2002. Hospitalizations for heart failure codes 429.4 and 997.1 were not included since these are for complications following cardiac procedures or surgeries.

We examined risk for hospitalization due to stroke, CHD or heart failure (separately) among participants who enrolled in Medicare. Statistical analysis methods were similar to those described in the text. However, since the times of exact onset for the binary outcome of first hospitalization for heart failure, CHD or stroke were not known (i.e., they could have occurred prior to 1984), logistic regression (not Cox regression) was used to estimate univariate and age- and sex-adjusted odds ratios and 95% confidence intervals, as well as the other measures of predictive utility for stroke, CHD or heart failure hospitalization. RESULTS

For the analyses of Medicare hospitalizations, 16,393 of the study sample attained Medicare eligibility and enrolled; of these, 3050 (18.6% of the Medicare cohort) had at least one hospitalization with a primary discharge diagnosis of stroke, 1367 had at least one hospitalization with a primary discharge diagnosis of myocardial infarction, and 2207 (13.5%) had at least one hospitalization with a primary discharge diagnosis of heart failure.

As with the analyses of stroke, CHD, and heart failure death, univariate analyses per 1- standard-deviation increment revealed similar risks associated with the single and summary measures of SBP, DBP, MAP, and MidBP, with lower risks associated with PP (Supplemental

Tables I to III). In the 2-term models, SBP was associated with higher risk than DBP or PP. SBP,

DBP, MAP and MidBP at baseline were more strongly associated and had better predictive utility for subsequent stroke or heart failure hospitalization at age 65 and older than did PP.

Adjustment for age and sex did not materially alter these patterns of association.

REFERENCES

1. Yan LL, Daviglus ML, Liu K, Stamler J, Wang R, Pirzada A, Garside DB, Dyer AR, Van

Horn L, Liao Y, Fries JF, Greenland P. Midlife body mass index and hospitalization and

mortality in older age. JAMA. 2006;295:190-198.

2. The international classification of diseases. 9th revision, clinical modification: ICD-9-CM.

Washington, DC: Department of Health and Human Services; 1980. DHHS Publication no.

(PHS) 80-1260. Supplemental Table I. Unadjusted Risks and Predictive Utilities* for Stroke Hospitalization after age 65, N=3,050, of Different Blood Pressure Measures at Baseline Blood OR (95% CI) P value Likelihood Ratio AIC BIC AUC Pressure per SD† χ2 Measure Single Measures SBP 1.26 (1.21-1.30) <0.001 145.6 15610.47 15625.88 0.57 DBP 1.24 (1.19-1.29) <0.001 109.0 15647.15 15662.56 0.56 Summary Measures PP 1.18 (1.13-1.22) <0.001 70.9 15685.19 15700.6 0.55 MAP 1.26 (1.22-1.31) <0.001 144.6 15611.49 15626.9 0.57 MidBP 1.27 (1.22-1.31) <0.001 150.5 15605.62 15621.03 0.57 2-component models SBP 1.20 (1.14-1.26) <0.001 151.4 15606.68 15629.79 0.57 DBP 1.07 (1.01-1.14) 0.02 SBP 1.34 (1.26-1.43) <0.001 151.4 15606.68 15629.79 0.57 PP 0.92 (0.86-0.99) 0.02 SBP 1.13 (1.03-1.24) 0.009 151.4 15606.68 15629.79 0.57 MAP 1.12 (1.02-1.24) 0.02 SBP 1.07 (0.93-1.23) 0.33 151.4 15606.68 15629.79 0.57 MidBP 1.18 (1.03-1.36) 0.02 DBP 1.20 (1.15-1.25) <0.001 151.4 15606.68 15629.79 0.57 PP 1.14 (1.09-1.18) <0.001 Cont. Table I cont. DBP 0.86 (0.76-0.96) 0.009 151.4 15606.68 15629.79 0.57 MAP 1.45 (1.30-1.63) <0.001 DBP 0.96 (0.88-1.04) 0.33 151.4 15606.68 15629.79 0.57 MidBP 1.31 (1.21-1.42) <0.001 PP 1.06 (1.01-1.11) 0.009 151.4 15606.68 15629.79 0.57 MAP 1.23 (1.17-1.28) <0.001 PP 1.02 (0.98-1.08) 0.33 151.4 15606.68 15629.79 0.57 MidBP 1.25 (1.19-1.31) <0.001 MAP 0.87 (0.65-1.15) 0.33 151.4 15606.68 15629.79 0.57 MidBP 1.45 (1.09-1.92) 0.009 Abbreviations: AIC indicates Akeke information criterion; AUC, area under the receiver-operating characteristic curve; BIC, Bayes’ information criterion; CI, confidence interval; DBP, diastolic blood pressure; HR, hazards ratio; MAP, mean arterial pressure ((SBP + 2*DBP)/3); MidBP, mid-blood pressure ((SBP + DBP)/2); PP, pulse pressure (SBP – DBP); SBP, systolic blood pressure; SD, standard deviation. *Higher values of the likelihood ratio χ2 and lower values of the AIC and BIC indicate better model fit and predictive utility; higher values of the AUC indicate better discrimination. †For each blood pressure measure, the SD are as follows: SBP 18.5mmHg, DBP 11.6mmHg, PP 13.2mmHg, MAP 12.8mmHg, MidBP 13.9mmHg. Supplemental Table II. Unadjusted Risks and Predictive Utilities* for CHD Hospitalization after age 65, N=1,367, by Different Blood Pressure Characteristics at Baseline Blood OR (95% CI) P value Likelihood Ratio AIC BIC AUC Pressure per SD† χ2 Measure Single Measures SBP 1.28 (1.22-1.35) <0.001 89.7 9321.72 9337.12 0.58 DBP 1.28 (1.22-1.35) <0.001 78.5 9332.86 9348.26 0.57 Summary Measures PP 1.18 (1.12-1.24) <0.001 37.4 9374.01 9389.42 0.54 MAP 1.30 (1.23-1.37) <0.001 96.2 9315.21 9330.62 0.58 MidBP 1.30 (1.23-1.36) <0.001 97.5 9313.91 9329.32 0.58 2-component models SBP 1.18 (1.10-1.27) <0.001 97.5 9315.89 9339.00 0.58 DBP 1.12 (1.03-1.22) 0.005 SBP 1.42 (1.30-1.55) <0.001 97.5 9315.89 9339.00 0.58 PP 0.88 (0.80-0.96) 0.005 SBP 1.08 (0.95-1.23) 0.249 97.5 9315.89 9339.00 0.58 MAP 1.21 (1.06-1.38) 0.005 SBP 0.99 (0.81-1.19) 0.878 97.5 9315.89 9339.00 0.58 MidBP 1.32 (1.09-1.60) 0.005 DBP 1.25 (1.18-1.32) <0.001 97.5 9315.89 9339.00 0.58 PP 1.13 (1.07-1.19) <0.001 Cont. Table II cont. DBP 0.91 (0.77-1.07) 0.249 97.5 9315.89 9339.00 0.58 MAP 1.42 (1.21-1.65) <0.001 DBP 1.01 (0.90-1.14) 0.878 97.5 9315.89 9339.00 0.58 MidBP 1.29 (1.15-1.44) <0.001 PP 1.04 (0.97-1.10) 0.249 97.5 9315.89 9339.00 0.58 MAP 1.27 (1.20-1.35) <0.001 PP 0.99 (0.93-1.06) 0.878 97.5 9315.89 9339.00 0.58 MidBP 1.30 (1.22-1.39) <0.001 MAP 1.03 (0.69-1.53) 0.878 97.5 9315.89 9339.00 0.58 MidBP 1.26 (0.85-1.86) 0.249

Abbreviations and notes as in Supplemental Table I. Supplemental Table III. Unadjusted Risks and Predictive Utilities* for Heart Failure Hospitalization after age 65, N=2,207, of Different Blood Pressure Measures at Baseline Blood OR (95% CI) P value Likelihood Ratio AIC BIC AUC Pressure per SD† χ2 Measure Single Measures SBP 1.36 (1.31-1.42) <0.001 212.9 12744.72 12760.12 0.59 DBP 1.33 (1.28-1.40) <0.001 159.0 12798.65 12814.06 0.58 Summary Measures PP 1.25 (1.20-1.31) <0.001 106.0 12851.63 12867.04 0.56 MAP 1.37 (1.32-1.43) <0.001 210.6 12747.00 12762.41 0.59 MidBP 1.37 (1.32-1.43) <0.001 219.2 12738.39 12753.8 0.59 2-component models SBP 1.28 (1.20-1.36) <0.001 220.7 12738.87 12761.99 0.59 DBP 1.10 (1.03-1.17) 0.005 SBP 1.48 (1.38-1.59) <0.001 220.7 12738.87 12761.99 0.59 PP 0.90 (0.84-0.97) 0.005 SBP 1.19 (1.07-1.32) 0.001 220.7 12738.87 12761.99 0.59 MAP 1.17 (1.05-1.30) 0.005 SBP 1.10 (0.94-1.29) 0.22 220.7 12738.87 12761.99 0.59 MidBP 1.25 (1.07-1.46) 0.005 DBP 1.28 (1.22-1.34) <0.001 220.7 12738.87 12761.99 0.59 PP 1.19 (1.14-1.24) <0.001 Cont. Table III cont. DBP 0.81 (0.71-0.92) 0.001 220.7 12738.87 12761.99 0.59 MAP 1.67 (1.47-1.89) <0.001 DBP 0.94 (0.85-1.04) 0.22 220.7 12738.87 12761.99 0.59 MidBP 1.45 (1.32-1.58) <0.001 PP 1.08 (1.03-1.14) 0.001 220.7 12738.87 12761.99 0.59 MAP 1.31 (1.25-1.38) <0.001 PP 1.04 (0.98-1.09) 0.22 220.7 12738.87 12761.99 0.59 MidBP 1.34 (1.27-1.42) <0.001 MAP 0.82 (0.59-1.13) 0.22 220.7 12738.87 12761.99 0.59 MidBP 1.67 (1.22-2.30) 0.001

Abbreviations and notes as in Supplemental Table I.