Summary Background Prevalence of smoking is increasing in women in some populations and is a risk factor for coronary heart disease. Whether smoking confers the same excess risk of coronary heart ...disease for women as it does for men is unknown. Therefore, we aimed to estimate the effect of smoking on coronary heart disease in women compared with men after accounting for sex differences in other major risk factors. Methods We undertook a systematic review and meta-analysis of prospective cohort studies published between Jan 1, 1966, and Dec 31, 2010, from four online databases. We selected cohort studies that were stratified by sex with measures of relative risk (RR), and associated variability, for coronary heart disease and current smoking compared with not smoking. We pooled data with a random effects model with inverse variance weighting, and estimated RR ratios (RRRs) between men and women. Findings We reviewed 8005 abstracts and included 26 articles with data for 3 912 809 individuals and 67 075 coronary heart disease events from 86 prospective trials. In 75 cohorts (2·4 million participants) that adjusted for cardiovascular risk factors other than coronary heart disease, the pooled adjusted female-to-male RRR of smoking compared with not smoking for coronary heart disease was 1·25 (95% CI 1·12–1·39, p<0·0001). This outcome was unchanged after adjustment for potential publication bias and there was no evidence of important between-study heterogeneity (p=0·21). The RRR increased by 2% for every additional year of study follow-up (p=0·03). In pooled data from 53 studies, there was no evidence of a sex difference in the RR between participants who had previously smoked compared with those who never had (RRR 0·96, 95% CI 0·86–1·08, p=0·53). Interpretation Whether mechanisms underlying the sex difference in risk of coronary heart disease are biological or related to differences in smoking behaviour between men and women is unclear. Tobacco-control programmes should consider women, particularly in those countries where smoking among young women is increasing in prevalence. Funding None.
Aims/hypothesis
The prevalence of diabetes and heart failure is increasing, and diabetes has been associated with an increased risk of heart failure. However, whether diabetes confers the same excess ...risk of heart failure in women and men is unknown. The aim of this study was to conduct a comprehensive systematic review with meta-analysis of possible sex differences in the excess risk of heart failure consequent to diabetes. Our null hypothesis was that there is no such sex difference.
Methods
A systematic search was conducted in PubMed for population-based cohort studies published between January 1966 and November 2018. Studies were selected if they reported sex-specific estimates of RRs for heart failure associated with diabetes, and its associated variability, which were adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratio of RRs (RRRs) for heart failure associated with diabetes.
Results
Data from 47 cohorts, involving 12,142,998 individuals and 253,260 heart failure events, were included. The pooled multiple-adjusted RR for heart failure associated with type 1 diabetes was 5.15 (95% CI 3.43, 7.74) in women and 3.47 (2.57, 4.69) in men, leading to an RRR of 1.47 (1.44, 1.90). Corresponding pooled RRs for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13).
Conclusions/interpretation
The excess risk of heart failure associated with diabetes is significantly greater in women with diabetes than in men with diabetes.
PROSPERO registration: CRD42019135246
Hypertension (HTN) is an established risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Whether sex differences in the effect of HTN on CKD and ESRD incidence exist ...remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative impact of HTN on CKD and ESRD risk in women compared with men.
We systematically searched Embase and PubMed for cohort studies until 24 July 2020. Studies were selected if they reported a sex-specific association between systolic blood pressure (SBP) and CKD or ESRD. Random effects meta-analyses with inverse variance weighting were used to pool sex-specific relative risks (RRs) and the women-to-men ratio of RRs (the RRR) for incident CKD and ESRD.
Data from six cohorts, including 2,382,712 individuals and 6856 incident CKD events, and 833 ESRD events, were included in the meta-analysis. The RR for incident CKD or ESRD associated with HTN (SBP ≥140 mmHg) versus ideal BP (SBP < 120 mmHg) was 1.56 (95% CI, 1.39-1.75) in women and 2.06 (95% CI, 1.64-2.60) in men. The RR for incident CKD or ESRD was 23% lower in women than in men RRR 0.77 95% CI, 0.63-0.95 with no significant heterogeneity between studies (p-value for Q test = 0.507, I
= 17.7%).
HTN confers about a fifth lower excess risk of incident CKD or ESRD in women than men. Sex differences in onset, duration, and severity of some risk factors, such as albuminuria, diabetes, cardiovascular disease, obesity, and socioeconomic status, may explain part of the excess risk in men. Another explanation could be that women might be under-diagnosed and less likely to initiate dialysis. Future studies are needed to demonstrate the mechanisms responsible for the observed sex difference.
Summary Background Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal ...disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. Methods For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. Findings We identified 19 trials including 44 989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0–8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% 95% CI 4–22), myocardial infarction (13% 0–24), stroke (22% 10–32), albuminuria (10% 3–16), and retinopathy progression (19% 0–34). However, more intensive treatment had no clear effects on heart failure (15% 95% CI −11 to 34), cardiovascular death (9% –11 to 26), total mortality (9% –3 to 19), or end-stage kidney disease (10% –6 to 23). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 95% CI 0·93–1·97). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 1·21–5·89, p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). Interpretation Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. Funding National Health and Medical Research Council of Australia.
Studies have suggested that women's reproductive factors are associated with the risk of cardiovascular disease (CVD); however, findings are mixed. We assessed the relationship between reproductive ...factors and incident CVD in the UK Biobank.
Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40-69 years across the UK. During 7 years of follow-up, 9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267 440 women and 215 088 men without a history of CVD at baseline. Cox regression models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated with reproductive factors.
Adjusted HRs (95% CI) for CVD were 1.10 (1.01 to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14 (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women and 1.03 (1.02 to 1.05) in men.
Early menarche, early menopause, earlier age at first birth, and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life. The relationship between the number of children and incident CVD was similar for men and women.
Aims/hypothesis
Diabetes has been shown to be a risk factor for some cancers. Whether diabetes confers the same excess risk of cancer, overall and by site, in women and men is unknown.
Methods
A ...systematic search was performed in PubMed for cohort studies published up to December 2016. Selected studies reported sex-specific relative risk (RR) estimates for the association between diabetes and cancer adjusted at least for age in both sexes. Random-effects meta-analyses with inverse-variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratios of RRs (RRRs) for all-site and site-specific cancers.
Results
Data on all-site cancer events (incident or fatal only) were available from 121 cohorts (19,239,302 individuals; 1,082,592 events). The pooled adjusted RR for all-site cancer associated with diabetes was 1.27 (95% CI 1.21, 1.32) in women and 1.19 (1.13, 1.25) in men. Women with diabetes had ~6% greater risk compared with men with diabetes (the pooled RRR was 1.06, 95% CI 1.03, 1.09). Corresponding pooled RRRs were 1.10 (1.07, 1.13) for all-site cancer incidence and 1.03 (0.99, 1.06) for all-site cancer mortality. Diabetes also conferred a significantly greater RR in women than men for oral, stomach and kidney cancer, and for leukaemia, but a lower RR for liver cancer.
Conclusions/interpretation
Diabetes is a risk factor for all-site cancer for both women and men, but the excess risk of cancer associated with diabetes is slightly greater for women than men. The direction and magnitude of sex differences varies by location of the cancer.
Summary Background Diabetes mellitus is a major cause of death and disability worldwide and is a strong risk factor for stroke. Whether and to what extent the excess risk of stroke conferred by ...diabetes differs between the sexes is unknown. We did a systematic review and meta-analysis to estimate the relative effect of diabetes on stroke risk in women compared with men. Methods We systematically searched PubMed for reports of prospective, population-based cohort studies published between Jan 1, 1966, and Dec 16, 2013. Studies were selected if they reported sex-specific estimates of the relative risk (RR) for stroke associated with diabetes, and its associated variability. We pooled the sex-specific RRs and their ratio comparing women with men using random-effects meta-analysis with inverse-variance weighting. Findings Data from 64 cohort studies, representing 775 385 individuals and 12 539 fatal and non-fatal strokes, were included in the analysis. The pooled maximum-adjusted RR of stroke associated with diabetes was 2·28 (95% CI 1·93–2·69) in women and 1·83 (1·60–2·08) in men. Compared with men with diabetes, women with diabetes therefore had a greater risk of stroke—the pooled ratio of RRs was 1·27 (1·10–1·46; I2 =0%), with no evidence of publication bias. This sex differential was seen consistently across major predefined stroke, participant, and study subtypes. Interpretation The excess risk of stroke associated with diabetes is significantly higher in women than men, independent of sex differences in other major cardiovascular risk factors. These data add to the existing evidence that men and women experience diabetes-related diseases differently and suggest the need for further work to clarify the biological, behavioural, or social mechanisms involved. Funding None.
Age-standardised rates of cardiovascular disease (CVD) are substantially higher in men than women. This explains why CVD has traditionally been seen as a "man's problem". However, CVD is the leading ...cause of death in women, worldwide, and is one of the most common causes of disability-adjusted life-years lost. In general, this is under-recognised and, in several ways, women are disadvantaged in terms of CVD. Both in primary and secondary prevention, there is evidence that women are undertreated, compared to men. Women often experience heart disease in a different way compared to men, and lack of recognition of this has been shown to have adverse consequences. Female patients of male cardiac physicians have been found to have worse outcomes than their male counterparts, with no such gender differential for female cardiologists. Clinical trials in CVD primarily recruit male patients, yet, it is well recognised that some drugs act differently in women and men. Diabetes and smoking, and perhaps other risk factors, confer a greater proportional excess cardiovascular risk to women than to men, whilst adverse pregnancies and factors concerned with the female reproductive cycle give women added vulnerability to CVD. However, women's health research is skewed towards mother and child health, an area where, arguably, the greatest public health gains have already been made, and breast cancer. Hence there is a need to redefine what is meant by "women's health" to encompass the whole lifecycle, with a stronger emphasis on CVD and other non-communicable diseases. Sex-specific analyses of research data should be the norm, whenever feasible.
To investigate sex differences in risk factors for incident myocardial infarction (MI) and whether they vary with age.
Prospective population based study.
UK Biobank.
471 998 participants (56% women; ...mean age 56.2) with no history of cardiovascular disease.
Incident (fatal and non-fatal) MI.
5081 participants (1463 (28.8%) of whom were women) had MI over seven years' mean follow-up, resulting in an incidence per 10 000 person years of 7.76 (95% confidence interval 7.37 to 8.16) for women and 24.35 (23.57 to 25.16) for men. Higher blood pressure indices, smoking intensity, body mass index, and the presence of diabetes were associated with an increased risk of MI in men and women, but associations were attenuated with age. In women, systolic blood pressure and hypertension, smoking status and intensity, and diabetes were associated with higher hazard ratios for MI compared with men: ratio of hazard ratios 1.09 (95% confidence interval 1.02 to 1.16) for systolic blood pressure, 1.55 (1.32 to 1.83) for current smoking, 2.91 (1.56 to 5.45) for type 1 diabetes, and 1.47 (1.16 to 1.87) for type 2 diabetes. There was no evidence that any of these ratios of hazard ratios decreased with age (P>0.2). With the exception of type 1 diabetes, the incidence of MI was higher in men than in women for all risk factors.
Although the incidence of MI was higher in men than in women, several risk factors were more strongly associated with MI in women compared with men. Sex specific associations between risk factors and MI declined with age, but, where it occurred, the higher relative risk in women remained. As the population ages and the prevalence of lifestyle associated risk factors increase, the incidence of MI in women will likely become more similar to that in men.
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