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Table 4 Association of reproductive characteristics with mortality from circulatory diseases in the EPIC study

From: Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study

   Circulatory disease (n = 2,404) Cerebrovascular disease (n = 808) Ischaemic heart disease (n = 732)
ICD-10 codes   I00–I99 I60–I69 I20–I25
Variable Value Cases / non-cases HRa (95 % CI) Cases / non-cases HRa (95 % CI) Cases / non-cases HRa (95 % CI)
Parous Yes 1,970 / 264,637 0.86 (0.76–0.96) 655 / 265,952 0.93 (0.76–1.13) 598 / 266,009 0.79 (0.65-0.97)
Number of FTPsb 1 374 / 47,810 1.00 (reference) 114 / 48,070 1.00 (reference) 117 / 48,067 1.00 (reference)
  2 799 / 126,649 0.92 (0.81–1.04) 281 / 127,167 1.06 (0.85–1.32) 240 / 127,208 0.91 (0.73-1.14)
  3 431 / 58,411 0.88 (0.76–1.02) 135 / 58,707 0.90 (0.70–1.17) 139 / 58,703 0.93 (0.73-1.20)
  4 198 / 17,124 0.95 (0.79–1.13) 66 / 17,256 1.03 (0.75–1.41) 48 / 17,274 0.74 (0.52-1.05)
  5 63 / 4,735 0.85 (0.65–1.12) 21 / 4,777 0.92 (0.57–1.48) 18 / 4,780 0.78 (0.47-1.29)
  ≥6 62 / 2,464 1.13 (0.85–1.50) 23 / 2,503 1.49 (0.93–2.39) 19 / 2,507 1.12 (0.67-1.88)
  P for trendc 0.85   0.42   0.29
Age at first FTP, yearsd ≤20 304 / 38,897 1.15 (0.99–1.34) 97 / 39,104 1.14 (0.86–1.50) 105 / 39,096 1.14 (0.86-1.51)
  21–23 497 / 70,825 1.11 (0.98–1.26) 150 / 71,172 0.96 (0.76–1.23) 140 / 71,182 0.96 (0.74-1.24)
  24–25 359 / 51,697 1.05 (0.92–1.20) 122 / 51,934 1.00 (reference) 106 / 51,950 1.00 (reference)
  26–30 557 / 75,370 1.00 (reference) 199 / 75,728 0.97 (0.78–1.23) 166 / 75,761 0.99 (0.77-1.26)
  ≥31 237 / 26,790 1.06 (0.90–1.23) 79 / 26,948 0.90 (0.67–1.21) 74 / 26,953 1.10 (0.81-1.49)
Breastfeedingd Ever 1,534 / 210,507 0.80 (0.70–0.91) 526 / 211,515 0.94 (0.74–1.21) 445 / 211,596 0.69 (0.54-0.87)
Breastfeeding, monthse ≤1 135 / 20,835 1.00 (reference) 38 / 20,932 1.00 (reference) 41 / 20,929 1.00 (reference)
  >1 to ≤3 282 / 41,403 1.16 (0.94–1.43) 101 / 41,584 1.47 (1.00–2.14) 86 / 41,599 1.22 (0.83-1.79)
  >3 to ≤6 276 / 43,251 1.05 (0.85–1.30) 93 / 43,434 1.20 (0.82–1.77) 91 / 43,436 1.22 (0.83-1.79)
  >6 to ≤12 359 / 49,662 1.02 (0.83–1.26) 115 / 49,906 1.10 (0.75–1.60) 102 / 49,919 0.99 (0.68-1.45)
  >12 to ≤18 184 / 24,118 0.98 (0.78–1.23) 69 / 24,233 1.18 (0.78–1.77) 51 / 24,251 0.94 (0.61-1.44)
  >18 287 / 28,936 1.04 (0.83–1.31) 110 / 29,113 1.28 (0.85–1.90) 71 / 29,152 0.92 (0.60-1.40)
  P for trendc 0.48   0.076   0.153
OC use in never or former Never 1,274 / 105,390 1.00 (reference) 467 / 106,197 1.00 (reference) 352 / 106,312 1.00 (reference)
smokers at baselinef Ever 427 / 143,935 0.85 (0.75–0.97) 144 / 144,218 0.80 (0.64–1.01) 102 / 144,260 0.87 (0.67-1.12)
  Formerg 397 / 125,478 0.84 (0.74–0.96) 129 / 125,746 0.78 (0.62–0.98) 100 / 125,775 0.87 (0.67-1.13)
  Currentg,h 22 / 13,075 1.48 (0.90–2.43) 13 / 13,084 2.62 (1.30–5.26) 2 / 13,095 -
Duration of OC use, yearsf,i ≤1 72 / 26,096 1.00 (reference) 23 / 26,145 1.00 (reference) 21 / 26,147 1.00 (reference)
  >1 to <5 72 / 31,247 0.95 (0.68–1.33) 23 / 31,296 0.95 (0.52–1.73) 21 / 31,298 0.97 (0.52-1.83)
  5 to <10 80 / 31,480 0.98 (0.70–1.36) 34 / 31,526 1.40 (0.80–2.44) 14 / 31,546 0.58 (0.29-1.16)
  10 to <15 84 / 21,797 1.22 (0.88–1.70) 22 / 21,859 1.08 (0.59–2.00) 22 / 21,859 1.09 (0.58-2.05)
  ≥15 70 / 19,032 1.14 (0.80–1.62) 30 / 19,072 1.63 (0.91–2.94) 15 / 19,087 0.96 (0.48-1.94)
  P for trendc 0.38   0.177   0.91
Age at menarche, years <12 325 / 47,412 1.00 (reference) 105 / 47,632 1.00 (reference) 107 / 47,630 1.00 (reference)
  12 411 / 67,956 0.84 (0.73–0.98) 132 / 68,235 0.80 (0.62–1.04) 123 / 68,244 0.80 (0.62-1.04)
  13 555 / 82,511 0.89 (0.77–1.02) 186 / 82,880 0.86 (0.67–1.09) 165 / 82,901 0.81 (0.63-1.03)
  14 559 / 68,815 0.91 (0.79–1.05) 189 / 69,185 0.88 (0.69–1.12) 164 / 69,210 0.80 (0.62-1.02)
  ≥15 494 / 50,019 0.83 (0.72–0.96) 165 / 50,348 0.79 (0.61–1.02) 160 / 50,353 0.80 (0.62-1.03)
  P for trendc 0.47   0.51   0.30
Age at natural menopause, yearsj ≤45 251 / 13,225 1.07 (0.91–1.25) 78 / 13,398 1.00 (0.75–1.32) 85 / 13,391 1.14 (0.86-1.50)
  46–50 499 / 34,410 1.00 (reference) 163 / 34,746 1.00 (reference) 157 / 34,752 1.00 (reference)
  51–52 189 / 15,410 0.79 (0.67–0.94) 68 / 15,531 0.83 (0.62–1.12) 43 / 15,556 0.58 (0.41-0.82)
  53–55 166 / 13,589 0.75 (0.63–0.90) 54 / 13,701 0.71 (0.52–0.97) 45 / 13,710 0.67 (0.48-0.94)
  >55 64 / 3,560 0.85 (0.65–1.11) 22 / 3,602 0.81 (0.51–1.28) 17 / 3,607 0.71 (0.42-1.18)
  P for trendc <0.001   0.088   <0.001
  1. FTP, Full term pregnancy; OCs, Oral contraceptives; ICD-10, International Statistical Classification of Diseases Injuries and Causes of Death (10th revision)
  2. aCox regression adjusted for menopausal status (where applicable) (premenopausal [Ref], perimenopausal/unknown menopause, postmenopausal and surgical postmenopausal (bilateral oophorectomy)), body mass index (<23, 23–24.9 [Ref], 25–29.9, 30–39.9, 40+ kg/m2), physical activity index (inactive [Ref], moderately inactive, moderately active, active, unknown), education status (none/primary school [Ref], technical/professional school, secondary school/longer education including university, or unknown), smoking status and intensity (never [Ref], current 1–15 cigarettes/day, current 16–25 cigarettes/day, current 26+ cigarettes/day, former quit ≤10 years, former quit 11–20 years, former quit >20 years, current pipe/cigar/occasional smoker, current/former missing timing, unknown), smoking duration (<10 [Ref], 10 to <20, 20 to <30, 30 to <40, 40+ years, unknown), and stratified by age (continuous) and study centre
  3. bFTP includes live births and stillbirths
  4. cP for trend-values are based on continuous variables: number of FTPs (1 to ≥10); age at menarche (≤8, 9–19, ≥20); age at menopause (<35, 35–60, >60)
  5. dAmong parous women
  6. eAmong parous women who had ever breastfed (sum of all FTPs)
  7. fRestricted to participants who were never or former smokers, therefore models were adjusted for the same factorsa and a modified smoking status/intensity variable (never [Ref], former quit ≤10 years, former quit 11–20 years, former quit >20 years, former missing quit years, occasional smoker)
  8. gDoes not add up to the total number of OC users because 3.7 % of OC users were missing their timing of use
  9. hOf 22 total circulatory disease deaths, 13 were due to cerebrovascular disease, 2 to ischaemic heart disease, and 7 to other circulatory-related causes (n = 2 ‘Pulmonary embolism without mention of acute cor pulmonale’, and one death for each cause ‘Essential (primary) hypertension’, ‘Other specified pulmonary heart diseases’, ‘Cardiac arrest, unspecified’, ‘Atrial fibrillation and flutter’ and ‘Phlebitis and thrombophlebitis of other deep vessels of lower extremities’)
  10. iAmong ever users of OCs
  11. jAmong postmenopausal women; exclusions included participants from Sweden (no data for hysterectomy/oophorectomy), those who had a surgical menopause (hysterectomy and/or unilateral/bilateral oophorectomy), or if information on surgical menopause was missing