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On mortality from ischemic heart disease in women with very late menopause
Journal of Clinical Epidemiology 53 (2000) 435–436
LETTER TO THE EDITOR
On mortality from ischemic heart disease in women with very late menopause Bjarne K. Jacobsena,*, Ivar Heuchb, Gunnar Kvålec a
Institute of Community Medicine, University of Tromsø, 9037 Tromsø, Norway b Department of Mathematics, University of Bergen, 5008 Bergen, Norway c Center for International Health, University of Bergen, 5021 Bergen, Norway Received 11 May 1999; accepted 19 May 1999
In the last years, several research groups have investigated the relationship between age at natural menopause and the risk of ischemic heart disease (IHD) [1–4]. A recent issue of this journal included an analysis of the relations between age at natural menopause and risk of ischemic heart disease [4]. It showed, like other recent studies exploring this topic, an increased mortality from ischemic heart disease in women with an early menopause. However, it also indicated that women with a very late menopause (56–60 years) have an increased risk of ischemic heart disease. The U-shaped relation was particularly pronounced in women who had never used post-menopausal estrogens [4]. Our follow-up of 19,000 Norwegian women, with more than 2700 deaths, is the largest study of the association between age at menopause and IHD mortality [1]. In this population, hardly any women used post-menopausal estrogens [1]. However, the possible increased risk in women with very late menopause was not really investigated as the top category for age at menopause included women who were ⬎52 years old at menopause. In retrospect, we acknowledge that essential features of the data set may have been lost by this procedure. Thus, we have reanalyzed our data, splitting this group into two categories; women aged 53–55 and ⭓56 years at menopause, respectively. The results from a Cox regression analysis are displayed in Table 1, and give a somewhat equivocal picture. In women aged less than 70 and in women aged 80 and above, the reanalysis does not support a U-shaped relation between age at natural menopause and mortality from ischemic heart disease. In the age group 70–79 years, however, a sta-
tistically significant U-shaped relation did emerge. The quadratic relations differed significantly over age groups (P ⫽ 0.002). The U-shaped relation was not, however, of the same magnitude as in the follow-up of California SeventhDay Adventist women [4]. The U-shaped relationship found in California SeventhDay Adventists and in one of the age groups in Norway, seems at present difficult to explain. In the follow-up of Adventists, the U-shaped relation was also found among the older women (80 and above) [4], which is at variance with our Norwegian data. Thus, more research is needed to determine whether the relation between age at menopause and risk of ischemic heart disease indeed is U-shaped. If it is, we are still at a loss to explain why an increased risk of ischemic heart disease should be seen among women with a very late menopause.
References [1] Jacobsen BK, Nilssen S, Heuch I, Kvåle G. Does age at natural menopause affect mortality from ischemic heart disease? J Clin Epidemiol 1997;50:475–9. [2] Jvan der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans MJC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet 1996;347:714–8. [3] Cooper GS, Sandler DP. Age at natural menopause and mortality. Ann Epidemiol 1998;8:229–35. [4] Jacobsen BK, Knutsen SF, Fraser GE. Age at natural menopause and total mortality and mortality from ischemic heart disease: The Adventist Health Study. J Clin Epidemiol 1999;52:303–7.
* Corresponding author. Tel.: +47-77-64-48-33; fax: +47-77-64-48-31. E-mail address: [email protected] (B. K. Jacobsen) 0895-4356/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0895-4356(99)00 1 1 5 - 8
436
B.K. Jacobsen et al. / Journal of Clinical Epidemiology 53 (2000) 435–436
Table 1 Death of ischemic heart disease and age at menopause; and mortality rate ratio (MRR) with 95% confidence interval (95% CI)a ⬍70 years
⬎79 year
Age at menopause
All women Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
⬍43 44–46 47–49 50–52 53–55 ⬎55 P-value for linear trend quadratic effectb
318 389 687 984 336 53
1.0 0.97 0.91 0.90 0.89 0.96
(0.84–1.12) (0.79–1.04) (0.79–1.02) (0.77–1.04) (0.72–1.28)
49 44 101 103 18 1
1.0 0.73 0.91 0.77 0.44 0.24
(0.49–1.10) (0.65–1.28) (0.55–1.08) (0.25–0.75) (0.03–1.75)
146 169 251 362 128 22
1.0 0.91 0.73 0.78 0.85 1.01
(0.73–1.13) (0.60–0.90) (0.64–0.94) (0.67–1.08) (0.65–1.59)
123 176 335 519 190 30
1.0 1.14 1.11 1.09 1.10 1.10
(0.90–1.43) (0.91–1.37) (0.89–1.32) (0.87–1.38) (0.73–1.63)
a
0.09 0.3
70–79 years
0.009 0.09
0.09 0.004
Among women with natural menopause, adjusted for attained age, county and occupational group. Quadratic effect in addition to linear effect.
b
0.7 0.5
LETTER TO THE EDITOR
On mortality from ischemic heart disease in women with very late menopause Bjarne K. Jacobsena,*, Ivar Heuchb, Gunnar Kvålec a
Institute of Community Medicine, University of Tromsø, 9037 Tromsø, Norway b Department of Mathematics, University of Bergen, 5008 Bergen, Norway c Center for International Health, University of Bergen, 5021 Bergen, Norway Received 11 May 1999; accepted 19 May 1999
In the last years, several research groups have investigated the relationship between age at natural menopause and the risk of ischemic heart disease (IHD) [1–4]. A recent issue of this journal included an analysis of the relations between age at natural menopause and risk of ischemic heart disease [4]. It showed, like other recent studies exploring this topic, an increased mortality from ischemic heart disease in women with an early menopause. However, it also indicated that women with a very late menopause (56–60 years) have an increased risk of ischemic heart disease. The U-shaped relation was particularly pronounced in women who had never used post-menopausal estrogens [4]. Our follow-up of 19,000 Norwegian women, with more than 2700 deaths, is the largest study of the association between age at menopause and IHD mortality [1]. In this population, hardly any women used post-menopausal estrogens [1]. However, the possible increased risk in women with very late menopause was not really investigated as the top category for age at menopause included women who were ⬎52 years old at menopause. In retrospect, we acknowledge that essential features of the data set may have been lost by this procedure. Thus, we have reanalyzed our data, splitting this group into two categories; women aged 53–55 and ⭓56 years at menopause, respectively. The results from a Cox regression analysis are displayed in Table 1, and give a somewhat equivocal picture. In women aged less than 70 and in women aged 80 and above, the reanalysis does not support a U-shaped relation between age at natural menopause and mortality from ischemic heart disease. In the age group 70–79 years, however, a sta-
tistically significant U-shaped relation did emerge. The quadratic relations differed significantly over age groups (P ⫽ 0.002). The U-shaped relation was not, however, of the same magnitude as in the follow-up of California SeventhDay Adventist women [4]. The U-shaped relationship found in California SeventhDay Adventists and in one of the age groups in Norway, seems at present difficult to explain. In the follow-up of Adventists, the U-shaped relation was also found among the older women (80 and above) [4], which is at variance with our Norwegian data. Thus, more research is needed to determine whether the relation between age at menopause and risk of ischemic heart disease indeed is U-shaped. If it is, we are still at a loss to explain why an increased risk of ischemic heart disease should be seen among women with a very late menopause.
References [1] Jacobsen BK, Nilssen S, Heuch I, Kvåle G. Does age at natural menopause affect mortality from ischemic heart disease? J Clin Epidemiol 1997;50:475–9. [2] Jvan der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans MJC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet 1996;347:714–8. [3] Cooper GS, Sandler DP. Age at natural menopause and mortality. Ann Epidemiol 1998;8:229–35. [4] Jacobsen BK, Knutsen SF, Fraser GE. Age at natural menopause and total mortality and mortality from ischemic heart disease: The Adventist Health Study. J Clin Epidemiol 1999;52:303–7.
* Corresponding author. Tel.: +47-77-64-48-33; fax: +47-77-64-48-31. E-mail address: [email protected] (B. K. Jacobsen) 0895-4356/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0895-4356(99)00 1 1 5 - 8
436
B.K. Jacobsen et al. / Journal of Clinical Epidemiology 53 (2000) 435–436
Table 1 Death of ischemic heart disease and age at menopause; and mortality rate ratio (MRR) with 95% confidence interval (95% CI)a ⬍70 years
⬎79 year
Age at menopause
All women Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
Deaths
MRR
(95% CI)
⬍43 44–46 47–49 50–52 53–55 ⬎55 P-value for linear trend quadratic effectb
318 389 687 984 336 53
1.0 0.97 0.91 0.90 0.89 0.96
(0.84–1.12) (0.79–1.04) (0.79–1.02) (0.77–1.04) (0.72–1.28)
49 44 101 103 18 1
1.0 0.73 0.91 0.77 0.44 0.24
(0.49–1.10) (0.65–1.28) (0.55–1.08) (0.25–0.75) (0.03–1.75)
146 169 251 362 128 22
1.0 0.91 0.73 0.78 0.85 1.01
(0.73–1.13) (0.60–0.90) (0.64–0.94) (0.67–1.08) (0.65–1.59)
123 176 335 519 190 30
1.0 1.14 1.11 1.09 1.10 1.10
(0.90–1.43) (0.91–1.37) (0.89–1.32) (0.87–1.38) (0.73–1.63)
a
0.09 0.3
70–79 years
0.009 0.09
0.09 0.004
Among women with natural menopause, adjusted for attained age, county and occupational group. Quadratic effect in addition to linear effect.
b
0.7 0.5