DM and CVD ; Overreview

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Relation of diabetes mellitus and cardiovascular diseases is well known, in this presentation , just overview of this close relation

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DM and Cardiovascular Diseases: Overview:

DM and Cardiovascular Diseases: Overview By Dr.Abdelsalam Sherif MD cardiology

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Genitourinary diseases Leading Causes of Death , Worldwide in 2002 Cardiovascular diseases Infectious and parasitic diseases Cancer Respiratory infections Respiratory diseases Unintentional injuries Perinatal conditions Digestive diseases Intentional injuries Neuropsychiatric conditions Diabetes mellitus Maternal conditions Congenital anomalies Nutritional deficiencies Others 0 2000 4000 6000 8000 10000 12000 14000 16000 18000 Number of deaths (x1000)

Major Causes of Death in Persons of All Ages in Low- and Middle-Income Regions:

Major Causes of Death in Persons of All Ages in Low- and Middle-Income Regions

Cardiovascular Risk Factors:

Cardiovascular Risk Factors 1.Non – modifiable Age Gender Hereditary 2.Modifiable Hypertension D.M Dyslipidemia Smoking Obesity Behavioral factors( stress, Type A) LVH ↑HR

Cardiovascular Risk factors:

C ardiovascular Risk factors Hypertension Dyslipidemia Diabetes Age Smoking Overweight Genetics/ Gender

Overall 75%of patients with type2 Diabetes die from cardiovascular diseases :

Overall 75% of patients with type2 Diabetes die from cardiovascular diseases

Type 2 diabetes increases the risk of cardiovascular disease:

Rates (per 10,000 person-year) Adjusted for age, race, income, cholesterol, systolic blood pressure, smoking Total CVD CHD Stroke Other CVD 75 50 25 0 Diabetes No diabetes Relative risk 3.0 3.2 2.8 2.3 Type 2 diabetes increases the risk of cardiovascular disease n = 342,815 n = 5,163

Postprandial hyperglycemia is a greater cardiovascular risk factor than elevated fasting glucose levels:

Postprandial hyperglycemia is a greater cardiovascular risk factor than elevated fasting glucose levels Incidence of myocardial infarction (per 1,000 patients) Postprandial blood glucose, P < 0.05 Fasting blood glucose, P = NS n = 1,139 11-year follow-up Glycemic control: Good Borderline Poor FPG (mmol/l): 4.4–6.1  7.8 > 7.8 PPG (mmol/l): 4.4–8.0  10.0 > 10.0 250 0 200 150 100 50

MRFIT: Impact of Diabetes on Cardiovascular Disease Mortality:

MRFIT: Impact of Diabetes on Cardiovascular Disease Mortality

DM and CAD:

DM and CAD

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Glycemic disorders Dyslipidemia - Low HDL - Small, dense LDL Hypertriglyceridemia Postprandial lipemia Hypertension Impaired thrombolysis -  PAI-1, fibrinogen Endothelial dysfunction/ inflammation -  CRP, MMP-9, adiponectin Microalbuminuria Visceral Obesity Insulin Resistance  Free Fatty Acids Atherosclerosis The Metabolic Syndrome: A Network of Atherogenic Factors Brunzell J, Hokanson J. Diabetes Care. 1999;22(Suppl 3):C10-C13. McFarlane S, et al. J Clin Endocrinol Metab . 2001;86(2):713-718. Frohlich M, et al. Diabetes Care . 2000;23(12):1835-1839. Kuusisto J, et al. Circulation. 1995;91:831-837. Parulkar AA, et al. Ann Intern Med. 2001;134:61-71. Hseuh WA, et al. Diabetes Care. 2001;24(2):392-397. Lebovitz H. Clin Chem . 1999;45(8B):1339-1345.

The presence of diabetes was associated with a higher CHD risk in the VA-HIT placebo group:

The presence of diabetes was associated with a higher CHD risk in the VA-HIT placebo group 36.5% 34.3% 23.8% 21%

Subjects with diabetes have a risk of CHD comparable to non-diabetic subject with prior MI:

Subjects with diabetes have a risk of CHD comparable to non-diabetic subject with prior MI

Diabetes increases the extent of macrovascular disease:

Incidence of multivessel disease (%) Diabetes increases the extent of macrovascular disease 80 0 60 40 20 No diabetes Diabetes n = 148 n = 923

HTN and DM:

HTN and DM

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NEJM 2000; 342:905 Diabetes Care 2005; 28:310 Am J Kid Dis 2007; 49 (Suppl 2):S74 Type 1 (¼ are HTN) At Diagnosis: 20-40% With Microalbuminuria: 30-50% With Macroalbuminuria: 65-88% Type 2 (½ are HTN) At Diagnosis: 50% With Microalbuminuria: 80% With Macroalbuminuria: >90% HTN in DM: Prevalence

PowerPoint Presentation:

WHO Fact Sheet World KSA 2000 2030 2000 2030 DM 171,000,000 366,000,000 890,000 2,523,000 Management of Hypertension in Diabetics HTN in DM: Prevalence 133,800,000 801,880 NOW Only 25 percent of patients with hypertension have adequate control of their blood pressure The Third National Health and Nutrition Evaluation Survey (NHANES III) 29% of diabetic individuals with hypertension were unaware of the diagnosis. 43% of diabetic individuals with hypertension were untreated. 55% of diabetic individuals on treatment had a blood pressure ≥140/90. 12% of diabetic individuals on treatment had a blood pressure <130/85. Am J Prev Med 22:42–48, 2002

HYPERTENSION INCREASES DM COMPLICATIONS:

HYPERTENSION INCREASES DM COMPLICATIONS Relative Risk of Complications Diabetes vs No Diabetes: CVD 2.0 – 4.0 ESRD 7.0 Diabetes   BP vs Diabetes CHD 3.0 Stroke 4.0 Retinopathy 2.0 Nephropathy 2.0 Neuropathy 1.6 Mortality 2.0 75% die from CVD JAMA 2004; 292:2495 Kid Internat 2000; 59:703 NEJM 2005; 352:341

Dyslipidemia In DM:

Dyslipidemia In DM

Feature of atherogenic dyslipidemia:

Feature of atherogenic dyslipidemia Atherogenic dyslipidemia is characterized by the following features: ~low HDL-C ~elevated TG ~elevated levels of small dense LDL particles Atherogenic dyslipidemia is commonly found in ~subjects with type 2diabetes ~subjects with the metabolic syndrome Atherogenic dyslipidemia is commonly associated with apro-thrombotic& pro-inflammatory state

Dyslipidemia is a common feature of type2 diabetes:

Dyslipidemia is a common feature of type2 diabetes The diabetic dyslipidemic profile is characterized by: Reduced HDL Elevated triglycerides A preponderance of atherogenic small ,dense LDL particles

Diabetes and disturbances to lipid subfractions:

Diabetes and disturbances to lipid subfractions Atherogenic, small, dense LDL cholesterol Cardioprotective, lipid-rich, HDL-2 cholesterol Lipid-poor, HDL-3 cholesterol

PowerPoint Presentation:

Etiology Epidemiology Pathophysiology Diagnosis Prevention Prognosis and therapy CHF and Diabetes Mellitus

Diabetes and Heart Failure: Current Knowledge:

Diabetes and Heart Failure: Current Knowledge

Etiology:

Etiology Risk factors  heart failure in diabetic patients:- 1) CAD 2) Arterial hypertension 3) Diabetic cardiomyopathy

Epidemiology:

Epidemiology The Framingham study firmly established the epidemiologic link between DM and HF, where, the risk of HF among diabetics: 2.5 folds in men. 5 folds in women. An overall prevalence of HF in diabetics is 12 % ( Community based studies) and > 30% of HF patients have DM ( multivariate analysis identified CHF as an independent predictor of type 2 DM).

Pathophysiology:

Pathophysiology According to ACC/AHA guidelines for management of heart failure, the presence of DM is regarded as:- 1) stage A HF (risk of HF). 2) stage B HF (structural abnormalities such as LVH without overt cardiac dysfunction LV dysfunction in DM may be Diastolic or systolic. LV diastolic dysfunction in type I DM may result from a) metabolic abnormalities. b) ↑ in FFA. c) carnitine deficiency. d) advanced glycation end products. e) changes in ca ++ homeostasis. g) insulin resistance. h) endothelial dysfunction

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While in type 2 DM, the LV diastolic dysfunction may result from:- a) cardiac autonomic neuropathy. b) apoptosis and necrosis. c) ↓ insulin-like growth factor. d) ↑transforming growth factor. e) ↑angiotensin II and aldesterone. So, mechanisms therefore occur on a myocardial, vascular and neuro-humoral level.

Therapeutic Approach:

Therapeutic Approach

Targets for common cardiovascular risk factors in people with diabetes :

Risk Factors Targets Dyslipidaemia Decrease LDL cholesterol levels (<100 mg/dl or 2.5 mmol/l*) Raise HDL cholesterol levels (>46 mg/dl or 1.2 mmol/l*) Lower triglycerides (<150 mg/dl or 1.7 mmol/l*) Hypertension Lower blood pressure (<135/85 mm Hg) Hyperglycemia Reduce hyperglycemia (HbAlc <7%) Targets for common cardiovascular risk factors in people with diabetes

Syst-Eur: Reduction in Event Rate in Adults (60 Years) With Diabetes:

Syst-Eur: Reduction in Event Rate in Adults ( 60 Years) With Diabetes

Good glycemic contorol is not enough:

Good glycemic contorol is not enough ( UKPDS ) GOOD GLYCEMIC CONTOROL Microvascular complication significant reductions Macrovascular complications no significant effect

Improved Glycemic Control Has Been Shown to Reduce the Risk of Complications:

Stratton IM et al. BMJ. 2000;321:405-412. Improved Glycemic Control Has Been Shown to Reduce the Risk of Complications According to the United Kingdom Prospective Diabetes Study (UKPDS) 35, Every 1% Decrease in A1C Resulted in: Decrease in risk of microvascular complications ( P <.0001) Decrease in risk of any diabetes-related end point ( P <.0001) Decrease in risk of MI ( P <.0001) Decrease in risk of stroke ( P =.04) 21% 14% 12% 37%

Intensive glycemic control reduces microvascular complications :

Intensive glycemic control reduces microvascular complications All microvascular endpoints Cataract extraction Retinopathy 25% P = 0.0099 24% P = 0.046 21% P = 0.015 Microalbuminuria 33% P = 0.000054

Tight BP Control vs. Tight Glucose Control:

Tight Glucose Control Tight BP Control * P < 0.05 -50 - -40 - -30 - 0 - Stroke Any DM End Point DM Death Microvascular Complications Reduction in Risk (%) UKPDS. BMJ. 1998:317;703-712 . -20 - -10 - Tight BP Control vs. Tight Glucose Control HTN in DM: Effect of BP Control

HOT: Cardiovascular Events by Target DBP in Diabetes Subgroup:

HOT: Cardiovascular Events by Target DBP in Diabetes Subgroup

Glycemic Control and Risk of Development of HF in Diabetes :

Glycemic Control and Risk of Development of HF in Diabetes

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