1. Hypertension and the |Metabolic Syndrome Karim Said Cardiology Department Cairo University

2. 54 –year old postmenopausal woman Diabetes mellitus 10 years On glibenclamide, 5 mg b.i.d Hypertesion 8 years On ACE-I FH DM (mother) HTN (mother, brother) IHD (father) Sedentary life

3. On her last visit to the diabetes clinic, a BP of 170/110 mmHg was found She is asymptomatic Compliant to ACE-I No recent drug intake

4. Clinical Examination BP: 160/104 mmHg &no postural hypotension Truncal obesity (BMI : 32 kg/m2) Mild hirsutism Acne over the back Bruit over the Rt. carotid artery S4 over the cardiac apex Weak bilateral ankle jerk Normal vibration sensation Fundus: GI

5. Possible causes of uncontrolled hypertension in this patient are :  Possible causes of uncontrolled hypertension in this patient are : 1. Development of diabetic nephropathy 2. Cushing syndrome 3. Renal artery stenosis 4. Essential hypertension 5. All of the above 6. Either 1 or 3

6. Diabetic nephropathy:  development or recent elevation of BP in a diabetic patient should raise the possibility of diabetic nephropathy.  HTN is found in 90% of pts with diabetic nephropathy Cushing syndrome  hypertension – diabetes – truncal obesity – hirsutism acne Renal artery stenosis  Rt. Carotid bruit Essential hypertension  still the most common cause

7. Blood Chemistry Fasting blood sugar : 160mg/dl HbA1c : 8 % Uric acid : 8.0 mg/dl Creatinine : 0.6 mg/dl Serum K : 3.9 mg/dl Fasting lipogram: Triglycerides: 406 mg/dl T. cholesterol: 205 mg/dl LDL: 106 mg/dl HDL: 42 mg/dl

8. Urinalysis Protein : ++++ Sugar : ++ WBC : 15 – 20 / HPF RBC : 10 / HPF Cells : epithelial Casts : none

9.  These urinalysis findings establish the diagnosis of diabetic nephropathy: 1. Yes 1. Yes 2. No 2. No

10. Comment: Presence of UTI:  can be the cause of proteinuria  interferes with the laboratory diagnosis of diabetic nephropathy  difficult glycaemic control

11. Urine culture : E-coli (10 x 10 5 /ml) Oral Norfloxacin (400 mg b.i.d) for 1 week Urinalysis: Protein: trace WBC: 1 –2 /HPF RBC: 1 – 2 /HPF 24 hour urinary albumin : 150 mg/24 h BP: 156/104 mmHg

12. Comment In diabetic nephropathy:  In diabetic nephropathy: hypertension usually manifest with macroalbuminuria (> 300mg/dl) In DM type 1 : HTN may occur with microalbuminuria ( < 300 mg/dl) Diabetic retinopathy is common

13. Albuminuria Microalbuminuria ( 30 – 300 mg/day) - increased CV risks - progression to macroalbumuria Macroalbuminuria ( > 300 mg /day) - risk of ESRD

14. Cardiovascular Mortality in Diabetic Patients

15.  The recommended initial screening test for Cushing syndrome in this patient is : 1. Serum cortisol level 2. ACTH stimulation test 3. Overnight dexamethasone suppression test

16.  This patient has clinical features of the metabolic syndrome : 1. Yes 2. No

17. Clinical features of metabolic syndrome (NCEP – ATP III) Feature Diagnostic criteria Blood pressure Blood pressure > 130/ 85 mmHg Fasting blood sugar Fasting blood sugar > 110 mg / dl Waist circumfrence Waist circumfrence male female >101 cm >88 cm Triglycerides Triglycerides > 150 mg / dl HDL HDL male female < 50 mg / dl < 40 mg / dl

18. Prevalence of metabolic syndromePrevalence of metabolic syndrome - 24% of whole population - 40% of people > 60 years - 80% of patients with type 2 diabetes

19. Hypertension in Metabolic Syndrome

20. Salt & water retension Potentiation of vasopressors (AII,VP, Endothelin) Endothelial dysfunction VSMCs proliferation Renal cell proliferation

21. Other features of metabolic syndrome Hyperuricaemia Hyperandrogenism Albumiuria Elevated CRP Fatty liver Polycystic ovary syndrome Hypercoagulability

24.  For management of hypertension in this patient: 1. Increase the dose of ACE-I 2. Add another antihypertensive agent 3. Shift to another antihypertensive agent

26. Best antihypertensive drug to be added :  Best antihypertensive drug to be added : 1. Beta blocker 2. Alpha blocker 3. Thiazide diuretic 4. Calcium channel blocker ( dihydropyridine) 5. Calcium channel blocker (Non dihydropyridine)

27. Comment Thiazide diuretics - improves CV outcomes(ALLHAT, SHIP) - volume overload – low renin status CCA - dihydropyridine: controversial - non-dihydropyridine: effective with proteinuria

28. Beta-BlockerBeta-Blocker UKPDS 39

29. Beta-BlockerBeta-Blocker UKPDS 39 Slight weight gain ↑withdrawal rate ↓ mortality rate (post –MI)

30. Alpha –blockerAlpha –blocker (ALLHAT: Doxazosin Vs. Chlothalidone) (ALLHAT: Doxazosin Vs. Chlothalidone) - Increased risk of CHF (114%) - Increased risk of CHF (114%) - Increased risk of stroke (20%) - Increased risk of stroke (20%) - Increaesd risk of angina (16%) - Increaesd risk of angina (16%)

31.  Target blood pressure in this patient: 1. <140/90 mmHg 2. <130/85 mmHg 3. <120/ 75 mmHg

32. UKPDS (tight BP control)

36.  Anti- diabetic therapy in this patient: 1. Continue on glibenclamide 2. Shift to metformin 3. Shift to glimepride 4. Shift to insulin

37. Comment Metformin UKPDS : Intensive glycaemic control in overweight type 2 DM patients :  32 % reduction in diabetes related endpoints  42 % in diabetes – related deaths  Does not induce weight gain  Fewer hypoglycaemic episodes

38.  Would you add aspirin to this patient ?: 1. Yes 2. No

39. ACE.I + hydrochlorothiazide ( 25mg) Metformin (850 mg, b.i.d) Aspirin (150 mg daily) Weight reduction Physical activity Low CHO deit

40. 3 months later : - Weight loss: 6 Kg - BP: 144/90 mm Hg - FBS: 138 mg/dl - HbA1C: 7.3% - Fasting lipogram : Triglycerides: 360mg/dl T. cholesterol: 202 mg/dl LDL: 103 mg/dl HDL: 40 mg/dl

41.  Would you suggest adding triglycerides lowering agent to this patient ?: 1. Yes 2. No

43. Comment Isolated Hypertriglyceridaemia  CAD present : fibrates may be prescribed especially in the presence of low HDL (VA –HIT)  ATP III : - DM : considered as CAD equivalent - Triglycerides: 200 – 499 mg/dl - Especially in the presence of low HDL - Glycaemic control is mandatory - Weight reduction & physical activity

44. Thank You