Metabolic Consequences of Anti Hypertensives: Is It Clinically Important?

Transcription

1 Metabolic Consequences of Anti Hypertensives: Is It Clinically Important?,FACA,FICA,MASH,FVBWG,MISCP CONSULTANT OF CARDIOLOGY DIRECTOR OF PORT-FOUAD HOSPITAL CCU

2 Consideration of antihypertensive agents on metabolic effects Inhibitors of the renin-angiotensin system (ACE Is and ARBs) Shown to have a protective effect on the incidence of newonset diabetes Calcium channel blockers Neutral metabolic effects Beta-blockers Increase metabolic abnormalities Diuretics Increase metabolic abnormalities Ratto E, et al. J Am Soc Nephrol 26; 17: S

3 Antihypertensive agents: Diuretics Beta- ACE Calcium Angiotensin- blockers inhibitors channel receptor blockers blockers Mean arterial pressure Lipid profile Unfavourable Unfavourable Neutral Neutral Neutral Insulin resistance or Decrease Increase No effect

4 Antihypertensive treatments and incidence of new-onset diabetes Study CAPPP CHARM INVEST INSIGHT LIFE ALLHAT HOPE ASCOT % higher incidence in patients using diuretics, β-blockers Diuretics, β-blockers 21% v captopril Placebo ± SOC 22% v candesartan ± SOC Atenolol ± HCTZ or 15% v verapamil SR ± HCTZ or trandolapril trandolapril Co-amilozide ± β-blocker 3% v nifedipine GITS Atenolol 25% v losartan Chlorthalidone 21% v amlodipine 43% v lisinopril Placebo ± SOC 34% v ramipril ± SOC Atenolol ± 3% v amlodipine ± perindopril bendroflumethiazide Hansson L, et al. Lancet 1999; 353: : Pfeffer MA, et al. Lancet 23; 362: : Pepine CJ, et al. JAMA 23; 29: : Brown MJ, et al. Lancet 2; 356: : Dählof B, et al. Lancet 22; 359: : ALLHAT Collaborative Research Group. JAMA 22; 288: : HOPE Investigators. N Engl J Med 2; 342: : Dählof B, et al. Lancet 25; 366: :

5 Antihypertensive treatment with diuretics increased the probability of new-onset diabetes 8 7 Probability of new-onset diabetes (%) Receiving diuretics* Not receiving diuretics Glucose concentration at baseline visit (mmol/l( mmol/l) Verdecchia P, et al. Hypertension 24; 43: : *More than 9% of diuretic users received HCTZ or chlorthalidone

6 ACEIs: Potential mechanisms of improved glucose metabolism Angiotensin I Bradykinin ACE/Kininase II Angiotensin II Degradation products ACE inhibitors Angiotensin II Bradykinin Skeletal muscle blood flow Glucose metabolism Nitric oxide Henriksen EJ, Jacob S. J Cell Physiol. 23;196:171-9.

7 LIFE: New Onset Diabetes Proportion of Patients With First Event, % Dahlöf B, et al. Lancet. 22;359: Intent-to-Treat Atenolol Losartan Adjusted Risk Reduction 25%, P=.1 Unadjusted Risk Reduction 25%, P=.1 25% Time, months

8 Antihypertensives and Diabetes Risk Atherosclerosis Risk in Communities (ARIC) Study 384 patients (45-65 years old) 6-year prospective study Medication Hazard Ratio 95% CI ACE inhibitor β-blocker 1.26* Calcium antagonist Thiazide *P <.5. Gress TW et al. N Engl J Med. 2;342:

9 New-Onset Diabetes Prevention With ACEIs or ARBs

10 RAAS activation contributes to obesity-related hypertension Obesity Renal medullary compression RAAS activation Leptin Renal vasodilation Sodium reabsorption SNS activation Volume expansion Arterial hypertension SNS = sympathetic nervous system Sharma AM. Hypertension. 24;44:12-19.

11 Plasma Catecholamines in Obesity Hypertension Norepinephrine Epinephrine 4 P < P <.5 pg/ml 2 pg/ml Normotensive (n = 27) Hypertensive (n = 43) Kunz I et al. Hypertension. 2;36:26-32.

12 Plasma Leptin in Obesity Hypertension Women Men 5 P = ng/ml 2 ng/ml 2 P < Normotensive (n = 27) Hypertensive (n = 43) Kunz I et al. Hypertension. 2;36:26-32.

13 Optimizing antihypertensive treatment in sibutramine-treated patients N = 171 with overweight/obesity* + HTN; Sibutramine vs placebo Weight BMI Waist circumference S PL S PL S PL S PL S PL S PL S PL S PL S PL lbs inches -8.8 kg/m NS Change from baseline Felodipine 5 mg/ramipril 5 mg Verapamil 18 mg/trandolapril 2 mg Metoprolol 95 mg/hctz 12.5 mg *BMI kg/m 2 ; P <.1 vs placebo; P <.2 vs placebo HTN = hypertension; S = sibutramine 15 mg; PL = placebo Scholze J et al. Circulation. 27;115:

14 Metabolic Consequences of Anti Hypertensives: Is It Clinically Important? YES Decisions about the management of patients with hypertension should not be made on their blood pressure alone. THE DYSMETABOLIC STATUS OF THE HYPERTENSIVE PATIENTS SHOULD BE BEFORE OUR DECISIONS.