Table 4:
Hazard ratio (HR) of ADRD by randomized group (3 study drugs) and other factors, calculated by competing risks regression model (1999 to 2017).
| Demographic | Alzheimer’s Disease (AD) | Other non-AD Dementias | All ADRD combined | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Unadjusted HR (95% CI) | P value | Adjusted* HR (95% CI) | P value | Unadjusted HR (95% CI) | P value | Adjusted* HR (95% CI) | P value | Unadjusted HR (95% CI) | P value | Adjusted* HR (95% CI) | P value | |
| Randomized group | ||||||||||||
| Chlorthalidone vs Amlodipine | 1.02 (0.94, 1.11) | 0.57 | 1.02 (0.93, 1.12) | 0.71 | 1.02 (0.97, 1.08) | 0.47 | 0.98 (0.92, 1.04) | 0.54 | 1.01 (0.96, 1.07) | 0.63 | 0.98 (0.92, 1.05) | 0.57 |
| Lisinopril vs. Amlodipine | 1.02 (0.93, 1.12) | 0.68 | 1.00 (0.89, 1.11) | 0.95 | 1.04 (0.97, 1.11) | 0.25 | 0.98 (0.91, 1.05) | 0.52 | 1.03 (0.97, 1.10) | 0.28 | 0.97 (0.90, 1.04) | 0.4 |
| Lisinopril vs. | 1.00 (0.92, 1.08) | 0.92 | 0.98 (0.89, 1.08) | 0.66 | 1.02 (0.96, 1.08) | 0.58 | 1.00 (0.93, 1.06) | 0.91 | 1.02 (0.97, 1.08) | 0.47 | 0.99 (0.93, 1.05) | 0.71 |
| ChlorthalidonE‡ | ||||||||||||
| Age group (as of 1/1/1999) | ||||||||||||
| Age <70 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Age 70–79 | 1.57 (1.44, 1.70) | <0.001 | 1.61 (1.46, 1.77) | <0.001 | 1.36 (1.29, 1.44) | <0.001 | 1.34 (1.27, 1.43) | <0.001 | 1.37 (1.30, 1.45) | <0.001 | 1.36 (1.28, 1.44) | <0.001 |
| Age 80+ | 1.96 (1.77, 2.17) | <0.001 | 1.92 (1.70, 2.17) | <0.001 | 1.88 (1.75, 2.02) | <0.001 | 1.83 (1.68, 1.99) | <0.001 | 1.93 (1.80, 2.07) | <0.001 | 1.86 (1.71, 2.01) | <0.001 |
| Gender | ||||||||||||
| Male | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Female | 1.41 (1.31, 1.51) | <0.001 | 1.25 (1.14, 1.36) | <0.001 | 1.26 (1.20, 1.32) | <0.001 | 1.19 (1.12, 1.26) | <0.001 | 1.27 (1.21, 1.33) | <0.001 | 1.20 (1.13, 1.28) | <0.001 |
| Race/Ethnicity | ||||||||||||
| Non-Black | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Black | 1.16 (1.08, 1.25) | <0.001 | 1.19 (1.09, 1.30) | <0.001 | 1.17 (1.12, 1.23) | <0.001 | 1.04 (0.98, 1.11) | 0.17 | 1.15 (1.10, 1.21) | <0.001 | 1.06 (1.00, 1.12) | 0.061 |
| Hispanic/Latino Ethnicity | ||||||||||||
| Non-Hispanic | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Hispanic | 1.03 (0.95, 1.12) | 0.47 | 1.08 (0.97, 1.20) | 0.16 | 0.54 (0.50, 0.58) | <0.001 | 0.54 (0.50, 0.59) | <0.001 | 0.66 (0.62, 0.71) | <0.001 | 0.68 (0.63, 0.73) | <0.001 |
| Education level | ||||||||||||
| >high school | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| ≤ High school | 1.12 (1.03, 1.22) | 0.006 | 1.01 (0.92, 1.11) | 0.83 | 1.04 (0.98, 1.10) | 0.17 | 1.04 (0.98, 1.11) | 0.2 | 1.06 (1.01, 1.12) | 0.022 | 1.03 (0.97, 1.10) | 0.32 |
| Treatment with antihypertensive drugs prior to trial baseline | ||||||||||||
| Untreated | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Treated | 0.96 (0.86, 1.08) | 0.51 | 0.91 (0.80, 1.04) | 0.17 | 1.03 (0.95, 1.12) | 0.43 | 0.98 (0.89, 1.07) | 0.64 | 1.03 (0.95, 1.12) | 0.42 | 0.97 (0.89, 1.07) | 0.57 |
| Aspirin use (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.90 (0.84, 0.97) | 0.004 | 0.95 (0.87, 1.04) | 0.3 | 1.00 (0.95, 1.05) | 0.93 | 0.97 (0.92, 1.03) | 0.35 | 0.98 (0.93, 1.03) | 0.37 | 0.97 (0.91, 1.03) | 0.29 |
| Women taking estrogen at trial baseline † | ||||||||||||
| No | 1.00 (reference) | ------- | -------- | 1.00 (reference) | ------- | -------- | 1.00 (reference) | ------- | -------- | |||
| Yes | 0.97 (0.86, 1.09) | 0.58 | ------- | -------- | 1.06 (0.97, 1.14) | 0.18 | ------- | -------- | 1.03 (0.95, 1.11) | 0.53 | ------- | -------- |
| HDL cholesterol <35 mg/dl (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.84 (0.76, 0.92) | <0.001 | 0.96 (0.86, 1.09) | 0.55 | 0.85 (0.79, 0.91) | <0.001 | 0.90 (0.83, 0.97) | 0.006 | 0.85 (0.80, 0.91) | <0.001 | 0.91 (0.85, 0.99) | 0.02 |
| Cigarette smoking at trial baseline | ||||||||||||
| Never smoker | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Current smoker | 0.66 (0.59, 0.74) | <0.001 | 0.74 (0.65, 0.84) | <0.001 | 0.77 (0.72, 0.83) | <0.001 | 0.84 (0.78, 0.92) | <0.001 | 0.77 (0.72, 0.82) | <0.001 | 0.85 (0.79, 0.93) | <0.001 |
| Former smoker | 0.77 (0.72, 0.83) | <0.001 | 0.90 (0.82, 0.99) | 0.024 | 0.88 (0.84, 0.92) | <0.001 | 0.92 (0.87, 0.98) | 0.008 | 0.87 (0.83, 0.91) | <0.001 | 0.93 (0.88, 0.99) | 0.021 |
| Diabetes classification (as of 1/1/1999) | ||||||||||||
| Non-diabetes | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Diabetes | 0.99 (0.93, 1.07) | 0.88 | 1.02 (0.93, 1.11) | 0.7 | 1.07 (1.02, 1.12) | 0.009 | 1.13 (1.07, 1.20) | <0.001 | 1.07 (1.02, 1.13) | 0.004 | 1.14 (1.07, 1.20) | <0.001 |
| History of Coronary Heart Disease (CHD) (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.90 (0.83, 0.97) | 0.006 | 0.97 (0.86, 1.09) | 0.63 | 0.99 (0.94, 1.04) | 0.73 | 0.97 (0.89, 1.05) | 0.39 | 0.99 (0.94, 1.04) | 0.58 | 0.97 (0.90, 1.05) | 0.46 |
| Atherosclerotic Cardiovascular Disease (ASCVD) at trial baseline | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 1.04 (0.97, 1.11) | 0.3 | 1.27 (1.11, 1.44) | <0.001 | 1.11 (1.06, 1.16) | <0.001 | 1.07 (0.98, 1.17) | 0.12 | 1.10 (1.05, 1.15) | <0.001 | 1.09 (1.00, 1.19) | 0.045 |
| History of Myocardial Infarction (MI) or stroke (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.93 (0.86, 1.01) | 0.095 | 0.86 (0.76, 0.96) | 0.008 | 1.12 (1.06, 1.18) | <0.001 | 1.08 (1.00, 1.17) | 0.043 | 1.10 (1.05, 1.16) | <0.001 | 1.07 (0.99, 1.15) | 0.11 |
| History of Coronary Artery Bypass Graft (CABG) (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.85 (0.77, 0.94) | 0.001 | 0.92 (0.80, 1.06) | 0.24 | 1.00 (0.94, 1.07) | 0.94 | 1.00 (0.91, 1.09) | 0.93 | 0.97 (0.91, 1.04) | 0.42 | 0.99 (0.91, 1.08) | 0.86 |
| Other ASCVD at trial baseline | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.98 (0.90, 1.06) | 0.55 | 0.80 (0.71, 0.90) | <0.001 | 1.08 (1.02, 1.14) | 0.004 | 1.01 (0.93, 1.09) | 0.87 | 1.06 (1.01, 1.12) | 0.019 | 0.98 (0.91, 1.06) | 0.69 |
| Major ST segment depression (as of 1/1/1999) | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.91 (0.80, 1.04) | 0.17 | 0.83 (0.70, 0.97) | 0.02 | 0.97 (0.89, 1.06) | 0.46 | 0.94 (0.84, 1.05) | 0.26 | 0.96 (0.88, 1.05) | 0.35 | 0.93 (0.83, 1.03) | 0.15 |
| Left ventricular hypertrophy (LVH) by Minnesota code (as of 1/1/1999) | ||||||||||||
| No/Soft LVH | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Hard LVH | 0.93 (0.77, 1.13) | 0.46 | 0.81 (0.65, 1.01) | 0.065 | 1.09 (0.96, 1.23) | 0.19 | 1.05 (0.91, 1.21) | 0.54 | 1.10 (0.97, 1.24) | 0.13 | 1.06 (0.92, 1.22) | 0.43 |
| Lipid Lowering Trial (LLT) Participant | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.97 (0.90, 1.05) | 0.47 | 0.96 (0.88, 1.05) | 0.39 | 0.95 (0.90, 1.01) | 0.084 | 0.98 (0.93, 1.05) | 0.61 | 0.96 (0.91, 1.01) | 0.14 | 0.98 (0.93, 1.04) | 0.58 |
| Obesity (BMI ≥ 30 kg/m2) at trial baseline | ||||||||||||
| No | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | ||||||
| Yes | 0.85 (0.80, 0.92) | <0.001 | 0.86 (0.79, 0.93) | <0.001 | 0.99 (0.94, 1.03) | 0.56 | 0.97 (0.92, 1.03) | 0.29 | 0.96 (0.91, 1.00) | 0.068 | 0.95 (0.90, 1.00) | 0.068 |
| Blood pressure change (latest BP reading prior to 1/1/1999 minus BP at trial baseline), per 10 mmHg | ||||||||||||
| Systolic BP | 1.00 (0.98, 1.02) | 0.86 | 0.99 (0.96, 1.02) | 0.41 | 1.01 (0.99, 1.02) | 0.29 | 1.00 (0.98, 1.02) | 0.81 | 1.01 (1.00, 1.02) | 0.14 | 1.00 (0.98, 1.02) | 0.83 |
| Diastolic BP | 1.03 (0.99, 1.06) | 0.13 | 1.02 (0.98, 1.07) | 0.34 | 1.02 (1.00, 1.04) | 0.082 | 1.02 (0.99, 1.05) | 0.23 | 1.03 (1.01, 1.05) | 0.007 | 1.03 (1.00, 1.06) | 0.075 |
Abbreviations: ADRD: Alzheimer’s Disease and Related Dementias; HR: Hazard Ratio; CI: Confidence Interval
Note:
*
Adjusted for each covariate shown, in addition to all others presented in the table,
‡
Contrast estimates were garnered from the same model, using a different reference group for randomized group (Chlorthalidone or Amlodipine),
†
Estrogen use was evaluated in women only, which prevented simultaneous inclusion of sex and estrogen as covariates.