Table 2.
Cox regression analysis of the association between incident Alzheimer’s disease and renin-angiotensin system inhibitors and confounding factors (N = 57,420).
| Characteristics | Number of subjects | Person-years | Number of events | Incidence ratea | Unadjusted HR (95% CI) | Adjusted HR (95% CI)b | value of p |
|---|---|---|---|---|---|---|---|
| RAS inhibitors | |||||||
| Non-users | 28,710 | 244,738 | 3,689 | 15.07 | Ref. | Ref. | |
| Users | 28,710 | 245,646 | 3,614 | 14.71 | 0.97 (0.93–1.02) | 0.99 (0.94–1.03) | 0.5886 |
| Sex | |||||||
| Men | 26,205 | 220,155 | 2,499 | 11.35 | Ref. | Ref. | |
| Women | 31,215 | 270,229 | 4,804 | 17.78 | 1.55 (1.48–1.63) | 1.29 (1.22–1.35) | <0.0001 |
| Age | |||||||
| Under 65 | 14,406 | 139,775 | 672 | 4.81 | Ref. | Ref. | |
| Between 65 and 80 | 37,607 | 318,706 | 5,616 | 17.62 | 3.87 (3.57–4.19) | 2.61 (2.41–2.83) | <0.0001 |
| Over 80 | 5,407 | 31,903 | 1,015 | 31.82 | 8.36 (7.58–9.22) | 5.71 (5.16–6.31) | <0.0001 |
| Insurance type | |||||||
| Health insurance | 52,408 | 451,995 | 6,484 | 14.35 | Ref. | Ref. | |
| Medical aid | 5,012 | 38,389 | 819 | 21.33 | 1.55 (1.45–1.67) | 1.06 (0.98–1.14) | 0.1288 |
| Comorbid diseases | |||||||
| Atherosclerosis | 3,801 | 30,269 | 933 | 30.82 | 2.28 (2.13–2.44) | 1.14 (1.06–1.22) | 0.0003 |
| Atrial fibrillation | 5,533 | 42,740 | 1,022 | 23.91 | 1.78 (1.66–1.90) | 1.08 (1.01–1.16) | 0.0243 |
| Bipolar disorder | 3,695 | 25,224 | 2,160 | 85.63 | 9.02 (8.57–9.49) | 1.21 (1.13–1.30) | <0.0001 |
| Cerebrovascular disease | 11,919 | 86,778 | 3,625 | 41.77 | 4.97 (4.75–5.21) | 2.16 (2.05–2.27) | <0.0001 |
| Depression | 8,247 | 58,952 | 3,637 | 61.69 | 8.03 (7.67–8.41) | 2.54 (2.40–2.69) | <0.0001 |
| Diabetes mellitus | 16,932 | 135,354 | 3,302 | 24.40 | 2.23 (2.13–2.34) | 1.40 (1.33–1.47) | <0.0001 |
| Dyslipidemia | 27,533 | 237,258 | 4,798 | 20.22 | 2.03 (1.93–2.13) | 1.46 (1.38–1.56) | <0.0001 |
| Hypertension | 34,998 | 289,386 | 5,526 | 19.10 | 2.21 (2.10–2.33) | 1.34 (1.27–1.42) | <0.0001 |
| Parkinson’s disease | 1,675 | 12,199 | 829 | 67.96 | 5.48 (5.10–5.89) | 1.31 (1.21–1.42) | <0.0001 |
| Schizophrenia | 1,752 | 10,923 | 1,119 | 102.44 | 9.57 (8.97–10.21) | 1.18 (1.10–1.27) | <0.0001 |
| Sleep disorder | 6,705 | 46,658 | 2,284 | 48.95 | 4.77 (4.54–5.01) | 1.48 (1.40–1.57) | <0.0001 |
| Traumatic brain injury | 1,791 | 12,303 | 753 | 61.20 | 4.95 (4.59–5.34) | 1.31 (1.21–1.42) | <0.0001 |
| Vascular dementia | 10,013 | 76,196 | 4,254 | 55.83 | 8.15 (7.78–8.54) | 3.17 (3.01–3.34) | <0.0001 |
| Concurrent medications | |||||||
| Antidepressants | 2,533 | 17,400 | 1,132 | 65.06 | 5.46 (5.13–5.82) | 1.21 (1.13–1.30) | <0.0001 |
| Antiepileptics | 405 | 2,710 | 189 | 69.74 | 5.27 (4.56–6.09) | 1.36 (1.17–1.57) | <0.0001 |
| Antihistamines | 2,251 | 13,229 | 979 | 74.00 | 6.54 (6.11–6.992) | 2.19 (2.04–2.36) | <0.0001 |
| Antiparkinsonian agents | 570 | 3,601 | 381 | 105.80 | 8.60 (7.75–9.53) | 1.28 (1.14–1.43) | <0.0001 |
| Antipsychotics | 3,691 | 23,943 | 2,353 | 98.28 | 12.50 (11.90–13.13) | 2.12 (1.97–2.28) | <0.0001 |
| Antispasmodics | 589 | 2,561 | 463 | 180.79 | 18.49 (16.81–20.34) | 2.69 (2.43–2.97) | <0.0001 |
| Benzodiazepines | 4,354 | 28,465 | 1,756 | 61.69 | 5.75 (5.45–6.07) | 1.48 (1.39–1.57) | <0.0001 |
| Beta–blockers | 14,498 | 120,723 | 2,506 | 20.76 | 1.61 (1.54–1.69) | 1.13 (1.07–1.18) | <0.0001 |
| Bladder antimuscarinics | 2,422 | 16,746 | 1,177 | 70.29 | 5.96 (5.59–6.34) | 1.95 (1.82–2.08) | <0.0001 |
| CCB (Dihydropyridine) | 15,813 | 135,062 | 2,794 | 20.69 | 1.62 (1.55–1.70) | 1.09 (1.04–1.15) | 0.0009 |
| CCB (Non–dihydropyridine) | 5,128 | 43,905 | 828 | 18.86 | 1.30 (1.21–1.39) | 1.10 (1.03–1.19) | 0.0091 |
| HMG–CoA reductase inhibitors | 25,227 | 226,480 | 3,922 | 17.32 | 1.31 (1.25–1.37) | 0.83 (0.79–0.88) | <0.0001 |
| Skeletal muscle relaxants | 771 | 4,191 | 549 | 130.99 | 11.68 (10.70–12.75) | 1.95 (1.78–2.15) | <0.0001 |
| Zolpidem | 2,380 | 14,746 | 1,224 | 83.01 | 7.55 (7.10–8.03) | 1.32 (1.23–1.42) | <0.0001 |
CCB, calcium channel blocker; CI, confidence interval; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; HR, hazard ratio; N, number; RAS, renin-angiotensin system. aIncident Alzheimer’s disease per 1,000 person-years. bAdjusted for sex, age, type of insurance, comorbid disease, concurrent medications, and follow-up duration.