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CVD IN TYPE-2 DIABETIC patients

Types and pathogenesis and treatment of cardiovascular diseas in diabetes

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CVD IN TYPE-2 DIABETIC patients

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  1. Diabetes and cardiovascular disease Professor / Mohammed Ahmed Bamashmos Professor of internal medicine and endocrinology Sanaa University

  2. Introduction The combination of type 2 diabetes and cardiovascular disease confers a high risk of cardiovascular events and mortality. Recent cardiovascular outcome trials provide persuasive evidence of reduced cardiovascular events and mortality when a SGLT2 inhibitor or GLP-1 agonist is added to standard care. This guideline provides a practical approach to optimise cardiovascular risk reduction in patients with type 2 diabetes and cardiovascular disease by prioritising prescription of these medications in patients under the care of the cardiology team.

  3. The combination of diabetes with atherosclerotic cardiovascular disease (CVD) confers a four-fold increase in the risk of mortality and a reduction in life expectancy of around 15 years in a patient of 60 years of age1. Around one quarter of patients admitted to hospital with acute coronary syndrome have diabetes2. In patients with established CVD, individuals with diabetes benefit symmetrically to those without disease from blood pressure reduction, lipid-modification, and anti-platelet therapy3. Despite major advances in overall survival following acute coronary syndrome over time, the gap in mortality between patients with and without diabetes has failed to improve4.

  4. Risk Factors of type 2diabetes in CVD • 1- poor glycemic control • 2- Hypoglycemia • 3- Glycemic variability • 4- Hypertension • 5- Dyslipidemia • 6- Obesity • 7- Insulin resistance • 8- Endothelial dysfunction • 9- Inflammation • 10- Oxidative stress

  5. Poor glycemic control • Poor glycemic control corresponds to a higher risk of complications: every 1% increase of glycated haemoglobin (HbA1C) above the threshold level (7%) is associated with a 38% increase in macrovascular events such as CVD

  6. Hypoglycemia • Several pathophysiological mechanisms have been proposed linking hypoglycemia to increased cardiovascular risk, including hemodynamic changes, myocardial ischemia, abnormal cardiac repolarization, cardiac arrhythmias, prothrombotic and proinflammatory effects, and induction of oxidative stress.

  7. Glycemic variability

  8. Hypertension

  9. Dyslipidemia

  10. Obesity

  11. Insulin resistance

  12. Endothelial dysfunction

  13. Inflammation

  14. Pathogenesis of CVD in Type-2 diabetic

  15. Types of Cardiovascular disease 1- coronary artery disease 2- Heart failure 3- cardiomyopathy 4- Arrhythmia

  16. Coronary artery disease Prevalence

  17. Pathogenesis

  18. Heart failure Prevalence

  19. Pathogenesis

  20. Interaction between type 2diabetes and HF

  21. Cardiomyopathy Prevalence

  22. Arrhythmia • Prevalence

  23. Pathogenesis

  24. The more apparent effect of SGLT2is is retained in subjects with atherosclerotic CV disease (HR 0.76; 95% CI, 0.69–0.84) and, though to a less extent, in those with multiple CV risk factors (HR 0.84; 95% CI, 0.69–1.01) as well as in those with a known history of HF (HR 0.71; 95% CI, 0.61–0.84) and those without (HR 0.79; 95% CI, 0.71–0.88) [[30]]. These results have been confirmed in real world studies. The CVD-Real study [[31]] identified after propensity matching, 309,056 patients equally split between those newly initiated on SGLT2is and those on other glucose-lowering agents. Use of SGLT2is was associated with lower rates of hHF (HR 0.61; 95% CI, 0.51–0.73; p < 0.001); death (HR 0.49; 95% CI, 0.41–0.57; p < 0.001) and hHF or death (HR 0.54; 95% CI, 0.48–0.60; p < 0.001). In OBSERVE-4D, 142,800 new users of canagliflozin, 110,897 new users of other SGLT2is, and 460,885 new users of non-SGLT2is were

  25. The study showed a HR for hHF with canagliflozin vs non-SGLT2i of 0.39 (95% CI, 0.26–0.60). Finally, in EMPRISE, after propensity-score matching, 16,443 patient pairs who initiated empagliflozin or sitagliptin were identified. The study showed that, compared with sitagliptin, empagliflozin decreased the risk of hHF by 50% (HR, 0.50; 95% CI, 0.28–0.91) over a mean follow-up of 5.3 months [[33]]. Altogether, these studies show that treatment with SGLT2is as compared to other glucose-lowering drugs is associated with a significantly lower risk of hHF, suggesting that the benefits seen with CVOTs may be a class effect applicable to a broad population of T2DM patients

  26. Heart failure is a heterogeneous condition encompassing at least two major categories: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). To which extent SGLT2is could exert a similar effect in both conditions is still a matter of active evaluation. Calculation of the number needed to treat (NNT) in DECLARE [[34]] seems to suggest a more evident beneficial effect in T2DM subjects with HFrEF (Fig. 1). This was, at least initially, confirmed by the results of the Dapa-HF study [[35]]. In 4,744 individuals with HF and ejection fraction <40%, those randomized to dapagliflozin had a 26% risk reduction of worsening heart failure (i.e. hospitalization or urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death (HR 0.74; 95

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