Hypertension and the |Metabolic Hypertension and the |Metabolic SyndromeSyndrome

Karim SaidCardiology 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 Possible causes of uncontrolled hypertension in this patient are :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 ChemistryBlood 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

UrinalysisUrinalysis

Protein : ++++Sugar : ++WBC :15 – 20 / HPFRBC : 10 / HPFCells : epithelialCasts : none

These urinalysis findings establish the These urinalysis findings establish the diagnosis of diabetic nephropathy: diagnosis of diabetic nephropathy:

1. Yes1. Yes 2. No2. No

Comment:

Presence of UTI: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 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

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

AlbuminuriaAlbuminuria

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

Cardiovascular Mortality in Diabetic PatientsCardiovascular Mortality in Diabetic Patients

The recommended initial screening test for The recommended initial screening test for Cushing syndrome in this patient is :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 This patient has clinical features of the metabolic syndrome : metabolic syndrome :

1. Yes 2. No

Clinical features of metabolic syndromeClinical features of metabolic syndrome(NCEP – ATP III)(NCEP – ATP III)

FeatureFeature Diagnostic criteriaDiagnostic criteria

• Blood pressureBlood pressure > 130/ 85 mmHg

• Fasting blood sugarFasting blood sugar > 110 mg / dl• Waist circumfrenceWaist circumfrence male female

>101 cm>88 cm

• TriglyceridesTriglycerides > 150 mg / dl

• HDLHDL 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

Hypertension in Metabolic Syndrome

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

Other features of metabolic syndromeOther features of metabolic syndrome

• Hyperuricaemia• Hyperandrogenism• Albumiuria• Elevated CRP• Fatty liver• Polycystic ovary syndrome• Hypercoagulability

For management of hypertension in this For management of hypertension in this patient: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-BlockerUKPDS 39UKPDS 39

• Beta-BlockerBeta-BlockerUKPDS 39UKPDS 39

Slight weight gain

↑withdrawal rate

↓ mortality rate (post –MI)

• Alpha –blocker Alpha –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: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: 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 endpoints42 % in diabetes – related deathsDoes not induce weight gainFewer hypoglycaemic episodes

Would you add aspirin to this patient ?: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 Would you suggest adding triglycerides lowering agent to this patient ?: 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

Thank YouThank You