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

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

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

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

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

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

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

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

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

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

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

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

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

Cardiovascular Mortality in Diabetic Patients

 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

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

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

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

Hypertension in Metabolic Syndrome

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

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

 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

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)

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

Beta-BlockerBeta-Blocker UKPDS 39

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

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%)

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

UKPDS (tight BP control)

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

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

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

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

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

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

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

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