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

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 : 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 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 105/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: • 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)

18. Prevalence 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. Hypertension in Metabolic Syndrome • 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 : 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. UKPDS 39 • Beta-Blocker

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

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