Table 1
Baseline characteristics and reproductive factors of female by cardiometabolic disease status.
| TOTAL (n = 189,411) | WITHOUT CMD (n = 172,160) | WITH CMD (n = 17,251) | P | SMD | |
|---|---|---|---|---|---|
| Age, y | 55.88 (7.98) | 55.49 (7.96) | 59.71 (7.18) | <0.001 | 0.557 |
| TDI | –1.47 (2.96) | –1.51 (2.93) | –1.01 (3.18) | <0.001 | 0.164 |
| Qualifications | |||||
| College | 32.7 | 33.7 | 22.5 | <0.001 | 0.250 |
| Ethnicity | |||||
| White | 91.3 | 91.3 | 91.3 | 0.922 | 0.001 |
| BMI, kg/m2 | 26.78 (4.96) | 26.55 (4.81) | 29.06 (5.78) | <0.001 | 0.472 |
| Waist circumference, cm | 83.84 (11.99) | 82.23 (11.67) | 90.01 (13.39) | <0.001 | 0.540 |
| Smoking status | <0.001 | 0.181 | |||
| Never | 60.0 | 60.6 | 53.3 | ||
| Previous | 31.3 | 31.1 | 33.5 | ||
| Current | 8.7 | 8.3 | 13.2 | ||
| Drinking status | 0.498 | 0.012 | |||
| Never | 19.7 | 19.8 | 19.5 | ||
| 1–3 times per month | 11.1 | 11.1 | 10.9 | ||
| 1–4 times per week | 48.8 | 48.7 | 49.2 | ||
| Daily | 20.4 | 20.4 | 20.3 | ||
| Age at menarche | 12.97 (1.60) | 12.98 (1.60) | 12.92 (1.68) | <0.001 | 0.041 |
| Group | <0.001 | 0.074 | |||
| <12 | 38.7 | 45.0 | 41.3 | ||
| 12–13 | 44.6 | 38.4 | 41.4 | ||
| >13 | 16.7 | 16.6 | 17.3 | ||
| Age at menopause | 49.79 (5.00) | 49.84 (4.92) | 49.38 (5.66) | <0.001 | 0.089 |
| Group | <0.001 | 0.119 | |||
| <46 | 20.6 | 20.1 | 24.2 | ||
| 46–49 | 31.5 | 31.7 | 30.4 | ||
| 50–51 | 19.7 | 20.0 | 17.3 | ||
| 52–53 | 13.2 | 13.3 | 12.0 | ||
| >53 | 15.1 | 14.9 | 16.2 | ||
| Reproductive lifespan | 36.82 (5.24) | 36.87 (5.16) | 36.44 (5.88) | <0.001 | 0.078 |
| Group | <0.001 | 0.101 | |||
| <33 | 21.1 | 20.8 | 24.4 | ||
| 33–35 | 19.4 | 19.4 | 18.8 | ||
| 36–38 | 28.4 | 28.7 | 25.7 | ||
| 39–40 | 15.0 | 15.1 | 14.3 | ||
| >40 | 16.2 | 16.1 | 16.9 | ||
| Age at first live birth | 25.49 (4.61) | 25.64 (4.62) | 24.08 (4.28) | <0.001 | 0.350 |
| Group | <0.001 | 0.347 | |||
| <22 | 27.3 | 26.1 | 38.7 | ||
| 22–23 | 16.0 | 15.8 | 18.1 | ||
| 24–26 | 24.9 | 25.7 | 22.7 | ||
| 27–29 | 18.1 | 18.7 | 12.9 | ||
| >29 | 13.6 | 14.3 | 7.5 | ||
| Age at last live birth | 30.36 (4.88) | 30.46 (4.87) | 29.46 (4.85) | <0.001 | 0.206 |
| Group | <0.001 | 0.210 | |||
| <26 | 22.3 | 21.6 | 29.0 | ||
| 26–28 | 22.9 | 22.7 | 24.8 | ||
| 29–30 | 15.7 | 15.8 | 14.4 | ||
| 31–34 | 23.5 | 23.9 | 19.5 | ||
| >34 | 15.6 | 16.0 | 12.3 | ||
| Number of live births | 1.80 (1.18) | 1.79 (1.17) | 1.99 (1.25) | <0.001 | 0.165 |
| Group | <0.001 | 0.154 | |||
| 0 | 32.1 | 32.5 | 28.2 | ||
| 1–2 | 62.0 | 61.9 | 62.7 | ||
| 3–4 | 5.5 | 5.2 | 8.3 | ||
| >4 | 0.4 | 0.4 | 0.8 | ||
| Number of stillbirths | <0.001 | 0.062 | |||
| 0 | 97.7 | 97.8 | 96.7 | ||
| 1 | 2.1 | 2.0 | 2.8 | ||
| > = 2 | 0.3 | 0.2 | 0.5 | ||
| Number of miscarriages or terminations | 0.009 | 0.025 | |||
| 0 | 68.7 | 68.7 | 69.0 | ||
| 1 | 20.8 | 20.9 | 20.0 | ||
| > = 2 | 10.5 | 10.5 | 11.0 | ||
| Oral contraceptive pill | <0.001 | 0.185 | |||
| No | 17.7 | 17.0 | 24.5 | ||
| Yes | 82.3 | 83.0 | 75.5 | ||
| HRT | <0.001 | 0.311 | |||
| No | 63.6 | 65.0 | 49.8 | ||
| Yes | 36.4 | 35.0 | 50.2 | ||
| hysterectomy | <0.001 | 0.250 | |||
| No | 82.8 | 83.8 | 73.6 | ||
| Yes | 17.2 | 16.2 | 26.4 | ||
| oophorectomy | <0.001 | 0.147 | |||
| No | 92.2 | 92.6 | 88.2 | ||
| Yes | 7.8 | 7.4 | 11.8 | ||
| SBP, mmHg | 134.54 (19.73) | 133.82 (19.47) | 141.74 (20.81) | <0.001 | 0.393 |
| CRP, mg/L | 2.58 (4.20) | 2.45 (4.04) | 3.86 (5.39) | <0.001 | 0.296 |
| Triglycerides, mmol/L | 1.52 (0.83) | 1.48 (0.80) | 1.88 (1.01) | <0.001 | 0.441 |
| Total cholesterol, mmol/L | 5.93 (1.10) | 5.92 (1.09) | 6.02 (1.17) | <0.001 | 0.090 |
| LDL, mmol/L | 3.67 (0.85) | 3.65 (0.84) | 3.78 (0.91) | <0.001 | 0.147 |
| HDL, mmol/L | 1.61 (0.37) | 1.62 (0.37) | 1.49 (0.37) | <0.001 | 0.341 |
| Lp(a), nmol/L | 45.30 (49.38) | 45.02 (49.16) | 48.16 (51.26) | <0.001 | 0.063 |
| Oestradiol, pmol/L | 541.11 (472.49) | 543.76 (472.30) | 492.57 (473.39) | <0.001 | 0.108 |
| TYG | 8.57 (0.51) | 8.55 (0.50) | 8.82 (0.53) | <0.001 | 0.523 |
| Lipid-lowing drug | <0.001 | 0.371 | |||
| No | 91.3 | 92.4 | 79.9 | ||
| Yes | 8.7 | 7.6 | 20.1 | ||
| Antihypertensive drug | <0.001 | 0.444 | |||
| No | 85.5 | 87.1 | 69.2 | ||
| Yes | 14.5 | 12.9 | 30.8 |
[i] Values are n (%) or mean (SD).
Abbreviations: SMD, standardized mean difference; TDI, Townsend Deprivation Index; BMI, body mass index; SBP, systolic blood pressure; CRP, C-reactive protein; LDL, low-density lipoprotein; HDL, high-density lipoprotein; Lp(a), lipoprotein(a); TYG, triglyceride-glucose index. HRT, menopausal hormone therapy.
Figure 1
The RCS curve of the association between (a) age at menarche, (b) age at menopause, (c) reproductive lifespan, (d) age at first live birth, (e) age at last live birth, (f) number of live births and cardiometabolic disease in women in the UK Biobank. HR and 95% CI.
Abbreviations: HR, hazard ratio; CI, confidence interval; CMD, cardiometabolic disease; AFB, age at first live birth; ALB, age at last live birth.
Adjusted for age, Townsend deprived index, qualifications, ethnicity, smoking status, drinking status, body mass index, systolic blood pressure, C-reactive protein, cholesterol, high-density lipoprotein, triglyceride-glucose index, hormone replacement therapy and use of oral contraceptives.
Table 2
Association of reproductive factors with incident cardiometabolic disease.
| REPRODUCTIVEFACTORS | MODEL 1 | MODEL 2 | ||||
|---|---|---|---|---|---|---|
| HR (95%CI) | P-VALUE | P FOR TREND | HR (95%CI) | P-VALUE | P FOR TREND | |
| Age at menarche, year | <0.001 | <0.001 | ||||
| <12 | 1.16 (1.12–1.20) | <0.001 | 1.04 (1.01–1.08) | 0.011 | ||
| 12–13 | Ref. | Ref. | ||||
| >13 | 1.07 (1.02–1.11) | 0.003 | 1.08 (1.04–1.13) | <0.001 | ||
| Age at menopausea, year | 0.029 | 0.020 | ||||
| <46 | 1.33 (1.26–1.41) | <0.001 | 1.22 (1.15–1.29) | <0.001 | ||
| 46–49 | 1.10 (1.04–1.16) | <0.001 | 1.08 (1.03–1.14) | 0.004 | ||
| 50–51 | Ref. | Ref. | ||||
| 52–53 | 1.02 (0.95–1.09) | 0.595 | 1.01 (0.94–1.08) | 0.856 | ||
| >53 | 1.07 (1.00–1.13) | 0.044 | 1.02 (0.95–1.08) | 0.627 | ||
| Reproductive lifespana, year | 0.388 | 0.036 | ||||
| <33 | 1.28 (1.22–1.35) | <0.001 | 1.19 (1.13–1.25) | <0.001 | ||
| 33–35 | 1.08 (1.02–1.14) | 0.005 | 1.08 (1.03–1.14) | 0.004 | ||
| 36–38 | Ref. | Ref. | ||||
| 39–40 | 1.03 (0.97–1.09) | 0.350 | 1.01 (0.95–1.07) | 0.696 | ||
| >40 | 1.05 (0.99–1.11) | 0.085 | 0.98 (0.93–1.04) | 0.591 | ||
| Age at first live birthb, year | <0.001 | <0.001 | ||||
| <22 | 1.34 (1.28–1.41) | <0.001 | 1.18 (1.12–1.24) | <0.001 | ||
| 22–23 | 1.11 (1.05–1.17) | <0.001 | 1.06 (1.00–1.12) | 0.041 | ||
| 24–26 | Ref. | Ref. | ||||
| 27–29 | 0.90 (0.84–0.95) | <0.001 | 0.94 (0.88–1.00) | 0.053 | ||
| >29 | 0.78 (0.72–0.84) | <0.001 | 0.85 (0.79–0.92) | <0.001 | ||
| Age at last live birthb, year | <0.001 | 0.269 | ||||
| <26 | 1.20 (1.14–1.28) | <0.001 | 1.12 (1.06–1.18) | <0.001 | ||
| 26–28 | 1.07 (1.01–1.13) | 0.026 | 1.04 (0.98–1.11) | 0.161 | ||
| 29–30 | Ref. | Ref. | ||||
| 31–34 | 0.98 (0.92–1.05) | 0.589 | 1.01 (0.95–1.07) | 0.829 | ||
| >34 | 0.99 (0.93–1.06) | 0.813 | 1.04 (0.97–1.11) | 0.261 | ||
| Number of live births | <0.001 | <0.001 | ||||
| 0 | 1.01 (0.98–1.05) | 0.554 | 1.01 (0.98–1.05) | 0.460 | ||
| 1–2 | Ref. | Ref. | ||||
| 3–4 | 1.32 (1.25–1.39) | <0.001 | 1.21 (1.15–1.28) | <0.001 | ||
| >4 | 1.48 (1.24–1.76) | <0.001 | 1.27 (1.07–1.52) | 0.006 | ||
| Number of stillbirths | <0.001 | 0.006 | ||||
| 0 | Ref. | Ref. | ||||
| 1 | 1.14 (1.04–1.25) | 0.005 | 1.06 (0.97–1.16) | 0.203 | ||
| > = 2 | 1.54 (1.24–1.91) | <0.001 | 1.39 (1.12–1.73) | 0.003 | ||
| Number of miscarriages or terminations | <0.001 | <0.001 | ||||
| 0 | Ref. | Ref. | ||||
| 1 | 1.03 (0.99–1.07) | 0.165 | 1.01 (0.98–1.05) | 0.509 | ||
| > = 2 | 1.18 (1.12–1.24) | <0.001 | 1.14 (1.09–1.20) | <0.001 | ||
| hysterectomy | ||||||
| No | Ref. | Ref. | ||||
| Yes | 1.39 (1.34–1.44) | <0.001 | 1.20 (1.15–1.24) | <0.001 | ||
| oophorectomy | ||||||
| No | Ref. | Ref. | ||||
| Yes | 1.30 (1.24–1.36) | <0.001 | 1.10 (1.05–1.16) | <0.001 | ||
[i] Abbreviations: HR, hazard ratio; CI, confidence interval.
Model 1 adjusted for age, Townsend deprived index, qualifications and ethnicity.
Model2 adjusted for covariables in model 1 plus smoking status, drinking status, body mass index, systolic blood pressure, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride-glucose index, menopausal hormone therapy and use of oral contraceptives.
aAmong postmenopausal women with valid menopausal age (n = 112,203).
bAmong parous women (more than 2 children) with live birth age information (n = 128,535).
Ref. = reference.
Figure 2
Forest plot of hazard ratios and 95% CIs for the association of reproductive factors and cardiometabolic disease stratified by age.
Abbreviations: HR, hazard ratio; CI, confidence interval.
Adjusted for Townsend deprived index, qualifications, ethnicity, smoking status, drinking status, body mass index, systolic blood pressure, C-reactive protein, cholesterol, high-density lipoprotein, triglyceride-glucose index, hormone replacement therapy and use of oral contraceptives.
Figure 3
Forest plot of hazard ratios and 95% CIs for the association of reproductive factors and cardiometabolic disease stratified by BMI.
Abbreviations: HR, hazard ratio; CI, confidence interval.
Adjusted for age, Townsend deprived index, qualifications, ethnicity, smoking status, drinking status, systolic blood pressure, C-reactive protein, cholesterol, high-density lipoprotein, triglyceride-glucose index, hormone replacement therapy and use of oral contraceptives.