Genere e rischio cardiovascolare nel diabete. Giuseppe Seghieri

Transcription

1 La salute e medicina di genere la ricerca sul campo focus su diabete e malattie croniche Genere e rischio cardiovascolare nel diabete. Giuseppe Seghieri Pistoia 7 giugno 2016, Ospedale San Jacopo _ Sala 2

2 Disclosure I have no actual or potential conflict of interest in relation to this presentation.

3 Percentage growth in age standardised diabetes prevalence, Peters SE et al, 2015

4 1. Does diabetes induce a more adverse cardiovascular disease (CVD) risk profile, and moreover are there differences in treatment of cardiovascular risk factors in diabetic women as compared to diabetic men? 2. Does diabetes induce a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men and when does the risk-window open? 3. Does the hormonal milieu explain sex-gender differences in diabetes associated excess risk of CVD? 4. Does sex-gender matter in diabetic microangiopathy retinopathy and nephropathy? 5. Are there relevant sex-gender differences in drug therapy of diabetes?

5 Differences in mean blood pressure and lipids by diabetic status in women and men. The STRONG Study. Howard BV et al., Diabetes Care, 1998 Women Men

6 Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women s Heart Health Study S. G. Wannamethee, Diabetologia, 2012

7 Mean body mass index by age at diagnosis of type 2 diabetes for men and women aged between 30 and 90 years at diagnosis and with BMI >25 kg/m2 from the Scottish Care Information Diabetes Collaboration (SCI-DC) dataset. Peters SE et al. 2015

8 Nutrition, Metabolism & Cardiovascular Diseases, 2015

9 Odds of receiving treatment, if indicated, for women relative to men (A), and effectiveness of therapy on treatment (B) Diabetes Care 28: , 2005

10 Rossi MC, et al. Diabetes Care, 2013

11 1. Does diabetes induce a more adverse cardiovascular disease (CVD) risk profile, and moreover are there differences in treatment of cardiovascular risk factors in diabetic women as compared to diabetic men? 2. Does diabetes induce a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men and when, in life, does the riskwindow open? 3. Does the hormonal milieu explain sex-gender differences in diabetes associated excess risk of CVD? 4. Does sex-gender matter in diabetic microangiopathy retinopathy and nephropathy? 5. Are there relevant sex-gender differences in drug therapy of diabetes?

12 Meta-analysis of three cohort studies demonstrating HRs of incident CAD, adjusted for traditional cardiovascular risk factors, in persons with versus without diabetes by sex. Kalyani RR, et al., Diabetes Care, 2014

13 Relative risk and women:men ratio of relative risks for coronary heart disease (CHD) and stroke in women and men with diabetes versus without diabetes. Peters SE et al., 2015

14 Incidence rate of first hospitalizations, expressed as events/person-years during the period 1 st January st December 2012 in Tuscany, for each cardiovascular disease Events No. Rate [(Events/1000person-yr (95% CI)] Males Females Males Females AMI No Diabetes 17,031 9, ( ) 1.25 ( ) Diabetes 3,708 2, ( ) 8.57 ( ) STROKE No Diabetes 16,573 15, ( ) 2.05 ( ) Diabetes 4,060 3, ( ) ( ) CHF No Diabetes 13,150 15, ( ) 1.95 ( ) Diabetes 4,072 4, ( ) ( ) LEA No Diabetes ( ) 0.09 ( ) Diabetes ( ) 1.32 ( ) MACE No Diabetes 44,865 38, ( ) 5.00 ( ) Diabetes 11,299 9, ( ) ( )

15 Relative risks for CVD women and men with diabetes versus without diabetes. T o t a l AMI N o. o f e v e n t s ; H R ( 9 5 % C I ) ; ( ) ; ( ) T o t a l CHF N o. o f e v e n t s ; H R ( 9 5 % C I ) ; ( ) ; ( ) ( ) > 8 5 y r ; ( ) ; ( ) y r ; ( ) ; ( ) y r ; ( ) ; ( ) y r ; ( ) ; ( ) y r ; ( ) ; ( ) y r ; ( ) > 8 5 y r y r y r y r y r y r ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) 8 5 ; ( ) ; ( ) N o. o f e v e n t s ; H R ( 9 5 % C I ) T o t a l > 8 5 y r ; ( ) ; ( ) ; ( ) ; ( ) N o. o f e v e n t s ; H R ( 9 5 % C I ) ; ( ) T o t a l ; ( ) ; ( ) > 8 5 y r y r y r y r LEA ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) y r y r y r Stroke ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) ; ( ) y r 4 2 ; ( ) ; ( ) ; ( ) y r ; ( ) y r 2 4 ; ( ) 9 1 ; ( ) y r ; ( ) ; ( )

16 Relative risks for CVD women with diabetes vsersus men with diabetes. T o t a l > 8 5 y r AMI N o. o f e v e n t s ; H R ( 9 5 % C I ) ; ( ) ; ( ) T o t a l > 8 5 y r CHF N o. o f e v e n t s ; H R ( 9 5 % C I ) ; ( ) ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) N o. o f e v e n t s ; H R ( 9 5 % C I ) N o. o f e v e n t s ; H R ( 9 5 % C I ) T o t a l > 8 5 y r LEA ; ( ) ; ( ) T o t a l > 8 5 y r Stroke ; ( ) ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( ) y r ; ( )

17 Pooled women-to-men ratios of standardised mortality ratios (SMR) for incident coronary heart disease and stroke, and for mortality from cardiovascular disease, renal disease, cancer, and accident and suicide in people with type 1 diabetes Huxley RR et al., Lancet Diabetes Endocrinol, 2015

18 Multiple-adjusted women-to-men RRRs for any dementia, vascular dementia, and nonvascular dementia, comparing individuals with diabetes to those without diabetes. RRR between men and women for vascular dementia: 1.19 ( ) Chatterjee S et al. Diabetes Care, 2016

19 Possible causes of the high cardiovascular risk in women with diabetes Nutrition, Metabolism & Cardiovascular Diseases (2010) 20, 474e480

20 1. Does diabetes induce a more adverse cardiovascular disease (CVD) risk profile, and moreover are there differences in treatment of cardiovascular risk factors in diabetic women as compared to diabetic men? 2. Does diabetes induce a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men? 3. Does the hormonal milieu explain sex-gender differences in diabetes associated excess risk of CVD? 4. Does sex-gender matter in diabetic microangiopathy retinopathy and nephropathy? 5. Are there relevant sex-gender differences in drug therapy of diabetes?

21 Benefits and Risks of the Two Hormone-Therapy Formulations Evaluated in the Women s Health Initiative during 5yr intervention period. NEJM, 2016

22 GPER= G protein-coupled estrogen receptor Meyer RM et al, Acta Physiol (Oxf), 2011.

23 1. Does diabetes induce a more adverse cardiovascular disease (CVD) risk profile, and moreover are there differences in treatment of cardiovascular risk factors in diabetic women as compared to diabetic men? 2. Does diabetes induce a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men? 3. Does the hormonal milieu explain sex-gender differences in diabetes associated excess risk of CVD? 4. Does sex-gender matter in diabetic microangiopathy - retinopathy and nepropathy? 5. Are there relevant sex-gender differences in drug therapy of diabetes?

24 Sex-related differences in the cumulative risk of PR over 40 years of type 1 diabetes according to age of diabetes onset 0-4 yr 5-9 yr yr >15 yr Harjutsalo V et al., 2011

25 Gender differences in the incidence and progression of diabetic retinopathy among Japanese patients with type 2 diabetes mellitus: A clinic-based retrospective longitudinal study Kajiwara A et al., DRCP, 2014 Women Men

26 Sex-related differences in the cumulative risk of ESRD over 40 years of type 1 diabetes according to age of diabetes onset 0-4 yr 5-9 yr yr >15 yr Harjutsalo V et al., 2011

27 Independent correlates of nonalbuminuric and albuminuric renal impairment (egfr <60 ml/min per 1.73m 2, stage 3 CKD). The RIACE study. Penno G et al., J Hypertens, 2011

28 1. Does diabetes induce a more adverse cardiovascular disease (CVD) risk profile, and moreover are there differences in treatment of cardiovascular risk factors in diabetic women as compared to diabetic men? 2. Does diabetes induce a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men? 3. Does the hormonal milieu explain sex-gender differences in diabetes associated excess risk of CVD? 4. Does sex-gender matter in diabetic microangiopathy retinopathy and nephropathy? 5. Are there relevant sex-gender differences in drug therapy of diabetes?

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30 Sex Differences in CVD Treatments and Interventions in DM

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32 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2013:

33 Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes The EMPA-REG trial (Zinman B et al.; NEJM, 2015) Placebo: Women : 30% Empagliflozin: Women: 29%

34 CONCLUSIONS Diabetes induces a more adverse cardiovascular disease (CVD) risk profile in women, combined with major differences in treatment of risk factors between men and women. Diabetes induces a greater excess risk of adverse cardiovascular disease (CVD) in women, as compared to men, in both type 1 and type 2, and this risk excess increases significantly in postmenopausal period. A different hormonal milieu may be important in yielding different outcomes in women, when compared to men. In type 1 diabetes the risk of microangiopathy (nephropathy and retinopathy) is significantly different between sexes, according to age of onset. There is the suggestion of a sexual dimorphism in the risk of albuminuric and non-albuminuric ESRD in type 2 diabetes.

35 CONCLUSIONS (cont d) There are substantial sex-gender differences in drug therapy of patients with diabetes: Women are more prone to have side effects after MET therapy, have different therapeutic outcomes after therapy with GLP-1 RA, have a significant risk excess of CHD after longstanding therapy with SUs and finally continue to be hugely underrepresented in CRT concerning cardiovascular benefits from medication with novel antidiabetic drugs. Further clarification and understanding of the mechanisms responsible for sex gender differences in the excess risk of complications associated with diabetes will be needed to improve and personalize the prevention and management of diabetes in clinical practise, in the global effort of reduce the rate of its hominous outcomes.

36 Thank you for your attention!