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  1. 1. <ul><li>Hypertension and the |Metabolic Syndrome </li></ul><ul><li>Karim Said </li></ul><ul><li>Cardiology Department </li></ul><ul><li>Cairo University </li></ul>
  2. 2. <ul><li>54 –year old postmenopausal woman </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>10 years </li></ul><ul><li>On glibenclamide , 5 mg b.i.d </li></ul><ul><li>Hypertesion </li></ul><ul><li>8 years </li></ul><ul><li>On ACE-I </li></ul><ul><li>FH </li></ul><ul><li>DM (mother) </li></ul><ul><li>HTN (mother , brother) </li></ul><ul><li>IHD (father) </li></ul><ul><li>Sedentary life </li></ul>
  3. 3. <ul><li>On her last visit to the diabetes clinic, a BP </li></ul><ul><li>of 170/110 mmHg was found </li></ul><ul><li>She is asymptomatic </li></ul><ul><li>Compliant to ACE-I </li></ul><ul><li>No recent drug intake </li></ul>
  4. 4. <ul><li>Clinical Examination </li></ul><ul><li>BP: 160/104 mmHg &no postural hypotension </li></ul><ul><li>Truncal obesity (BMI : 32 kg/m2) </li></ul><ul><li>Mild hirsutism </li></ul><ul><li>Acne over the back </li></ul><ul><li>Bruit over the Rt. carotid artery </li></ul><ul><li>S4 over the cardiac apex </li></ul><ul><li>Weak bilateral ankle jerk </li></ul><ul><li>Normal vibration sensation </li></ul><ul><li>Fundus: GI </li></ul>
  5. 5. <ul><li>Possible causes of uncontrolled hypertension in this patient are : </li></ul><ul><li>1. Development of diabetic nephropathy </li></ul><ul><li>2. Cushing syndrome </li></ul><ul><li>3. Renal artery stenosis </li></ul><ul><li>4. Essential hypertension </li></ul><ul><li>5. All of the above </li></ul><ul><li>6. Either 1 or 3 </li></ul>
  6. 6. <ul><li>Diabetic nephropathy: </li></ul><ul><li>development or recent elevation of BP in a diabetic patient should raise the possibility of diabetic nephropathy. </li></ul><ul><li>HTN is found in 90% of pts with diabetic nephropathy </li></ul><ul><li>Cushing syndrome </li></ul><ul><li>hypertension – diabetes – truncal obesity – hirsutism acne </li></ul><ul><li>Renal artery stenosis </li></ul><ul><li>Rt. Carotid bruit </li></ul><ul><li>Essential hypertension </li></ul><ul><li>still the most common cause </li></ul>
  7. 7. <ul><li>Blood Chemistry </li></ul><ul><li>Fasting blood sugar : 160mg/dl </li></ul><ul><li>HbA1c : 8 % </li></ul><ul><li>Uric acid : 8.0 mg/dl </li></ul><ul><li>Creatinine : 0.6 mg/dl </li></ul><ul><li>Serum K : 3.9 mg/dl </li></ul><ul><li>Fasting lipogram: </li></ul><ul><li>Triglycerides: 406 mg/dl </li></ul><ul><li>T. cholesterol: 205 mg/dl </li></ul><ul><li>LDL: 106 mg/dl </li></ul><ul><li>HDL: 42 mg/dl </li></ul>
  8. 8. <ul><li>Urinalysis </li></ul><ul><li>Protein : ++++ </li></ul><ul><li>Sugar : ++ </li></ul><ul><li>WBC : 15 – 20 / HPF </li></ul><ul><li>RBC : 10 / HPF </li></ul><ul><li>Cells : epithelial </li></ul><ul><li>Casts : none </li></ul>
  9. 9. <ul><li>These urinalysis findings establish the diagnosis of diabetic nephropathy: </li></ul><ul><li>1. Yes </li></ul><ul><li>2. No </li></ul>
  10. 10. <ul><li>Comment: </li></ul><ul><li>Presence of UTI: </li></ul><ul><li>can be the cause of proteinuria </li></ul><ul><li>interferes with the laboratory diagnosis of diabetic nephropathy </li></ul><ul><li>difficult glycaemic control </li></ul>
  11. 11. <ul><li>Urine culture : E-coli (10 x 10 5 /ml) </li></ul><ul><li>Oral Norfloxacin (400 mg b.i.d) for 1 week </li></ul><ul><li>Urinalysis: </li></ul><ul><li>Protein: trace </li></ul><ul><li>WBC: 1 –2 /HPF </li></ul><ul><li>RBC: 1 – 2 /HPF </li></ul><ul><li>24 hour urinary albumin : 150 mg/24 h </li></ul><ul><li>BP: 156/104 mmHg </li></ul>
  12. 12. <ul><li>Comment </li></ul><ul><li>In diabetic nephropathy: </li></ul><ul><li>hypertension usually manifest with macroalbuminuria (> 300mg/dl) </li></ul><ul><li>In DM type 1 : HTN may occur with microalbuminuria </li></ul><ul><li>( < 300 mg/dl) </li></ul><ul><li>Diabetic retinopathy is common </li></ul>
  13. 13. Albuminuria <ul><li>Microalbuminuria ( 30 – 300 mg/day) </li></ul><ul><li>- increased CV risks </li></ul><ul><li>- progression to macroalbumuria </li></ul><ul><li>Macroalbuminuria ( > 300 mg /day) </li></ul><ul><li>- risk of ESRD </li></ul>
  14. 14. Cardiovascular Mortality in Diabetic Patients
  15. 15. <ul><li>The recommended initial screening test for Cushing syndrome in this patient is : </li></ul><ul><li>1. Serum cortisol level </li></ul><ul><li>2. ACTH stimulation test </li></ul><ul><li>3. Overnight dexamethasone suppression test </li></ul>
  16. 16. <ul><li>This patient has clinical features of the metabolic syndrome : </li></ul><ul><li>1. Yes </li></ul><ul><li>2. No </li></ul>
  17. 17. Clinical features of metabolic syndrome (NCEP – ATP III) < 50 mg / dl < 40 mg / dl <ul><li>HDL </li></ul><ul><li>male </li></ul><ul><li>female </li></ul>> 150 mg / dl <ul><li>Triglycerides </li></ul>>101 cm >88 cm <ul><li>Waist circumfrence </li></ul><ul><li>male </li></ul><ul><li>female </li></ul>> 110 mg / dl <ul><li>Fasting blood sugar </li></ul>> 130/ 85 mmHg <ul><li>Blood pressure </li></ul>Diagnostic criteria Feature
  18. 18. <ul><li>Prevalence of metabolic syndrome </li></ul><ul><li>- 24% of whole population </li></ul><ul><li>- 40% of people > 60 years </li></ul><ul><li>- 80% of patients with type 2 diabetes </li></ul>
  19. 19. Hypertension in Metabolic Syndrome
  20. 20. Hypertension in Metabolic Syndrome <ul><li>Salt & water retension </li></ul><ul><li>Potentiation of vasopressors (AII,VP, Endothelin) </li></ul><ul><li>Endothelial dysfunction </li></ul><ul><li>VSMCs proliferation </li></ul><ul><li>Renal cell proliferation </li></ul>
  21. 21. <ul><li>Other features of metabolic syndrome </li></ul><ul><li>Hyperuricaemia </li></ul><ul><li>Hyperandrogenism </li></ul><ul><li>Albumiuria </li></ul><ul><li>Elevated CRP </li></ul><ul><li>Fatty liver </li></ul><ul><li>Polycystic ovary syndrome </li></ul><ul><li>Hypercoagulability </li></ul>
  22. 24. <ul><li>For management of hypertension in this patient: </li></ul><ul><li>1. Increase the dose of ACE-I </li></ul><ul><li>2. Add another antihypertensive agent </li></ul><ul><li>3. Shift to another antihypertensive agent </li></ul>
  23. 26. <ul><li>Best antihypertensive drug to be added : </li></ul><ul><li>1 . Beta blocker </li></ul><ul><li>2. Alpha blocker </li></ul><ul><li>3. Thiazide diuretic </li></ul><ul><li>4. Calcium channel blocker ( dihydropyridine) </li></ul><ul><li>5. Calcium channel blocker (Non dihydropyridine) </li></ul>
  24. 27. <ul><li>Comment </li></ul><ul><li>Thiazide diuretics </li></ul><ul><li>- improves CV outcomes(ALLHAT , SHIP) </li></ul><ul><li>- volume overload – low renin status </li></ul><ul><li>CCA </li></ul><ul><li>- dihydropyridine: controversial </li></ul><ul><li>- non-dihydropyridine: effective with proteinuria </li></ul>
  25. 28. <ul><li>Beta-Blocker </li></ul>UKPDS 39
  26. 29. <ul><li>Beta-Blocker </li></ul>Slight weight gain ↑withdrawal rate ↓ mortality rate (post –MI) UKPDS 39
  27. 30. <ul><li>Alpha –blocker </li></ul><ul><li>(ALLHAT: Doxazosin Vs. Chlothalidone) </li></ul><ul><li>- Increased risk of CHF (114%) </li></ul><ul><li>- Increased risk of stroke (20%) </li></ul><ul><li>- Increaesd risk of angina (16%) </li></ul>
  28. 31. <ul><li>Target blood pressure in this patient: </li></ul><ul><li>1. <140/90 mmHg </li></ul><ul><li>2. <130/85 mmHg </li></ul><ul><li>3. <120/ 75 mmHg </li></ul>
  29. 32. UKPDS (tight BP control)
  30. 36. <ul><li>Anti- diabetic therapy in this patient: </li></ul><ul><li>1. Continue on glibenclamide </li></ul><ul><li>2. Shift to metformin </li></ul><ul><li>3. Shift to glimepride </li></ul><ul><li>4. Shift to insulin </li></ul>
  31. 37. <ul><li>Comment </li></ul><ul><li>Metformin </li></ul><ul><li>UKPDS : Intensive glycaemic control in overweight type 2 DM patients : </li></ul><ul><li>32 % reduction in diabetes related endpoints </li></ul><ul><li>42 % in diabetes – related deaths </li></ul><ul><li>Does not induce weight gain </li></ul><ul><li>Fewer hypoglycaemic episodes </li></ul>
  32. 38. <ul><li>Would you add aspirin to this patient ?: </li></ul><ul><li>1. Yes </li></ul><ul><li>2. No </li></ul>
  33. 39. <ul><li>ACE.I + hydrochlorothiazide ( 25mg) </li></ul><ul><li>Metformin (850 mg , b.i.d) </li></ul><ul><li>Aspirin (150 mg daily) </li></ul><ul><li>Weight reduction </li></ul><ul><li>Physical activity </li></ul><ul><li>Low CHO deit </li></ul>
  34. 40. <ul><li>3 months later : </li></ul><ul><li>- Weight loss: 6 Kg </li></ul><ul><li>- BP: 144/90 mm Hg </li></ul><ul><li>- FBS: 138 mg/dl </li></ul><ul><li>- HbA1C: 7.3% </li></ul><ul><li>- Fasting lipogram : </li></ul><ul><li>Triglycerides: 360mg/dl </li></ul><ul><li>T. cholesterol: 202 mg/dl </li></ul><ul><li>LDL: 103 mg/dl </li></ul><ul><li>HDL: 40 mg/dl </li></ul>
  35. 41. <ul><li>Would you suggest adding triglycerides lowering agent to this patient ?: </li></ul><ul><li>1. Yes </li></ul><ul><li>2. No </li></ul>
  36. 43. <ul><li>Comment </li></ul><ul><li>Isolated Hypertriglyceridaemia </li></ul><ul><li>CAD present : fibrates may be prescribed especially in the presence of low HDL (VA –HIT) </li></ul><ul><li>ATP III : </li></ul><ul><li>- DM : considered as CAD equivalent </li></ul><ul><li>- Triglycerides: 200 – 499 mg/dl </li></ul><ul><li>- Especially in the presence of low HDL </li></ul><ul><li>- Glycaemic control is mandatory </li></ul><ul><li>- Weight reduction & physical activity </li></ul>
  37. 44. Thank You
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