Hypertension

1. Hypertension J. B. Handler, M.D. Physician Assistant Program University of New England

2. NSAID- non steroidal anti-inflammatory drug Na- sodium Cl- chloride Ca- calcium TC- total cholesterol A2- aortic component of the 2nd heart sound ACEI-angiotensin converting enzyme inhibitor CO- cardiac output RAAS- renin-angiotensin aldosterone system DM- diabetes mellitus SA- sinoatrial AV- atrioventricular BPH- benign prostatic hypertrophy SVR- systemic vascular resistance HTN- hypertension BP- blood pressure JNC- Joint National Committee HF- heart failure D/C-discontinue SVR  PVR PAD- peripheral arterial disease Abbreviations

3. Overview • Over 50 million Americans effected • Only 25% are adequately controlled • Marked prevalence in the elderly • Morbidity: cardiovascular diseaseand cerebrovascular disease • Definition: Systolic  140 Diastolic  90 • Optimal: Systolic < 120 Diastolic<80 Some exceptions

4. Classification • Essential (primary/idiopathic) hypertension- 95% all cases, etiology unknown; 2x incidence in black populations. • Secondary hypertension: 5%- renal, renovascular, endocrine, and congenital etiologies. • Early vs. Late hypertension- labile vs. sustained.

5. Pathogenesis: Contributory Factors • Genetic • Environmental factors: diet, sodium/salt intake, cigarette smoking, alcohol, weight • Sympathetic nervous system hyperactivity- young patients with HTN • Renin activation of RAAS. Low vs. high renin hypertension • Defect in natriuresis • Intracellular Na+ and Ca++ • Insulin resistance and metabolic syndrome (endocrine system)

6. Exacerbating Factors • Obesity • Excess Na intake • Cigarette smoking (norepinephrine) • NSAIDS • Excess alcohol

7. Secondary Hypertension • Estrogen use: activity of RAA system volume expansion. • Renal disease • Renal vascular HTN • Endocrine HTN • Cushings disease/syndrome • Pheochromocytoma • Primary hyperaldosteronism • Coarctation of the aorta- congenital • HTN in pregnancy To be covered during Endocrine System

8. Intrinsic Renal Disease • Any form of chronic renal parenchymal disease can result in hypertension. • Volume expansion and/or activity of RAA system. • Hypertension accelerates progression of renal insufficiency. • Treatment depends on etiology- often requires multiple drugs and/or dialysis.

9. Renal Vascular HTN • Renal Artery Stenosis: marked  of renin • 2 forms: fibromuscular hyperplasia (FMH) and atherosclerosis • FMH presents in young adults- BP markedly elevated; renal function preserved; arteriography diagnostic; angioplasty/stent beneficial in treatment. • Atherosclerosis: Older patients- BP elevated and unresponsive to meds; renal function often impaired; intervention may or may not help; long term med Rx necessary.

10. HTN: End Organ Disease • Heart • Coronary Heart Disease risk factor • LVH – diastolic dysfunction • Heart failure-  incidence from hypertension alone in last 25 years • Cerebrovascular Disease • Peripheral Arterial Disease • Renal Disease

11. LVH and Hypertension • Major compensatory mechanism to LV pressure overload. • Decreased LV compliance results in diastolic dysfunction. • Identified by Echocardiography in 50% of all hypertensives. • Powerful predictor of prognosis, morbidity, mortality, and cardiac events once present. • Regresses with aggressive treatment.

12. LVH NYerRN

13. Cerebrovascular Disease • HTN is the major predisposing cause of stroke. • Cerebral infarction secondary to atherosclerosis/thromboembolism. • Intracerebral hemorrhage  rupture of microaneurysms from BP. • Strokes more closely correlated with systolic than diastolic pressure.

14. Renal Disease • Nephrosclerosis: Progressive renal insufficiency; more common in black populations, especially in the presence of DM. • Reduced incidence with aggressive BP control. • HTN accelerates all other causes of chronic renal insufficiency.

15. Nephrosclerosis Images.google.com

16. Clinical Findings • Usually asymptomatic. A.M. headaches may occur. • Late findings include: -Symptoms related to LVH: Diastolic dysfunction (SOB, DOE). -Symptoms related to cerebral involvement- TIA, stroke, hemorrhage. -Symptoms related to cardiac involvement- MI, angina, HF.

17. Physical Exam • B.P >120/80 vs >140/90 (see below). • Retinal changes: Narrowing of arterioles (A/V < .50)A-V nicking- (arteriosclerosis) Silver or copper wired appearanceHemorrhages or exudatesPapilledema • CV exam often unremarkable • Pulses- Compare upper to lower. • Bruits indicate atherosclerotic disease; may involve femorals, aorta, carotids, and renal arteries.

18. Hypertensive Retinopathy

19. Lab Testing • Urinalysis: Looking for cells, casts, protein • Renal function: Creatinine, BUN • Electrolytes: Na, K, Cl, HCO3 • FBS • Lipids: TC, LDL, HDL, Triglycerides • Uric Acid • Baseline ECG • Cardiac Echo/Doppler if indicated (LVH by ECG, symptoms)

20. BP Classification JNC-7 • Prehypertension: S-120-139 D-80-89. • Stage I*: S-140-159 D-90-99. • Stage II*: S> 160 D>100. • Most patients will ultimately require 2 or more meds to reach goal BP, especially thosewith Stage II HTN. *Avg BP X 3 or more separate readings

21. Goals of Therapy • Decrease endpoints, not BP alone. • Endpoints: MI, Stroke, LVH, PAD, all cause/cardiac mortality, HF and renal failure. • Reduce cardiovascular risk for CHD. • Treatment of high risk groups:Diabetes MellitusChronic Renal Disease: Cr>1.3 woman; Cr> 1.4 men or microalbuminuria Goal is < 130/80.

22. Goals of Therapy • Aggressive treatment of other co-morbid states: Diabetes Mellitus and diabetic nephropathy, HF, dyslipidemia, CHD. • Keep it simple: Find drugs that address more than one co-morbidity. • Examples: ACEI for HTN and LV dysfunction ß-blocker for HTN & angina • Focus primarily on Systolic BP as this is the most important target for reducing morbidity and mortality. • BP=CO x SVR

23. BP Reduction and Morbidity • Decrease stroke incidence by 35-40%. • Decrease new onset heart failure by 50%. • Decrease MI incidence by 20-25%.

24. Non-Pharmacologic Rx • Diet*: Low in fat, sat fat and dairy foods; high in fruits, vegetables, fiber. • Weight reduction where indicated • Decreased alcohol intake • Decreased Na intake: <6 gram NaCl • Smoking cessation • Aerobic activity in sedentary individuals *DASH Diet: Dietary Approach to Stop Hypertension

25. Drug Therapy • At least 7 classifications of drugs used in treatment of hypertension. • Many of these classifications can be used as initial therapy but thiazide diuretics are the recommended 1st choice for majority of patients. • Must consider cost, side effects, compelling indications, compliance, other co-morbid states, and drug interactions when choosing drug therapy.

26. Diuretics • Cost-effective initial therapy. • 1st line therapy and should be part of any multi-drug combination. • Initial effects via decreased plasma volume; chronic effects via decreased SVR.

27. Diuretics • More potent in blacks, elderly and obese. More effective in smokers. • Thiazide-Type (HCTZ, Chlorthalidone, Indapamide): Once daily, effective in low dosage; work well in combination therapy with other agents. HCTZ 12.5-25mg/D. • Chlorthalidone more potent than HCTZ • Most effective in isolated systolic HTN. • Avoid in patients with hyponatremia and gout.

28. Thiazides-Adverse Effects • Hypokalemia: Often need to supplement K with diet or KCL. • Hyperuricemia: May precipitate gout. • Abnormalities of lipids (triglycerides, LDL) and glucose are usually minor. • Potassium sparing agents: spironolactone, amiloride or triamterene have mild diuretic effects, but may be combined with thiazides in some individuals with marked hypokalemia.

29. Beta Blocking Agents • Decrease BP by decreasing CO (-inotropic effect and HR). SVR increases, renin levels decrease. • Less effective in black populations and in elderly. • Very useful in patients with HTN and other co-morbid conditions that benefit from ß-blockade: angina pectoris, post MImortality, HFmortality, essential tremor, migraine headaches, arrhythmias/sudden death (class II anti-arrhythmic)

30. Pharmacologic Properties • B1 Selectivity: Cardioselective in low/mod dosage (Metoprolol, Atenolol, others). • Lipid solubility: CNS effects may result in both benefit (see below) and adversity (side effects). • Water soluble agents do not cross into brain (atenolol, others); better tolerated. • Alpha Blocking activity (Labetalol, Carvedilol). • Nitric oxide mediated vasodilation (below)

31. Nebivolol (Bystolic) • New (2008) selective B-blocker with vasodilating properties. • Nitric oxide mediated vasodilation • Loses selectivity in high doses • Similar BP lowering to other B-blockers- mild to moderate HTN. • Efficacy in heart failure, but not yet FDA approved. • Improves erectile function compared to other B-blockers.

32. Pharmacologic Properties • Mortality and other “end-point” benefits (post MI, HF) applicable primarily to lipid soluble ß-blockers. • CNS effects may be reason for mortality (protection from malignant arrhythmias- Vtach, Vfib) post MI and contributes to mortality in HF. This protection does not carry over to hydrophilic ß-blockers like atenolol. • ß-blockers less effective for LVH regression (vs. other agents).

33. Side Effects of ß-Blockers • Exacerbation of bronchospasm (non-selective). • Suppress SA node and AV conduction (bradycardia, AV block). • May worsen acute HF; but clearly beneficial for patients with chronic compensated & stable HF and low ejection fraction- mortality. • May worsen advanced PAD and rest pain. • Mask signs of hypoglycemia in Type I diabetics. • CNS: Fatigue, nightmares, depression, sexual dysfunction- lipid soluble ß-blockers.

34. ß-Problems and the Future • 2005: Meta-analysis on 13 RCT: ß-blocker vs other anti-hypertensives or placebo as 1st line monotherapy for HTNin patients without heart disease. • RR of stroke: 16% higher for pts Rx’d with ß-blockers compared to other drugs. • Message: ß-Blockers should not be used as 1st line monotherapy of HTN in patients without heart disease. OK as 2nd/3rd line agent for HTN.

35. ACE Inhibitors • Very popular; multiple indications beyond hypertension. • Inhibit renin-angiotensin-aldosterone system and: • Inhibit Bradykinin degradation • Stimulate vasodilating prostaglandin synthesis. • Useful as initial Rx or when added to other drugs for HTN.

36. ACE Inhibitors • Anti-hypertensive efficacy significantly improved when combined with diuretic synergistic effects. • Captopril, Enalapril, Lisinopril, Benezapril, Ramipril and others.

37. ACEI and Other Disease • Antihypertensive of choice in diabetics, often with other drugs. • Beneficial in diabetics with proteinuria or renal dysfunction even without HTN. • HTN and LV dysfunction • HF (cornerstone of therapy) with loop diuretic. • Asymptomatic normotensive patients with LV dysfunction prevent remodeling. • Post MI patients with LV dysfunction prevent remodeling.

38. Side Effects and Cost • Few side effects • Dry non-productive cough in up to 20%, but only 5% D/C the drug. • Hyperkalemia may occur in patients on supplemental K. • Angioedema: rare • All ACEI’s are available in generic form ing cost.

39. Angiotensin II Receptor Blockers • Block angiotensin II receptor • Newer ARB’s (Candesartan, Valsartan, Irbesartan) have similar BP lowering efficacy to ACE Inhibitors (at  cost). • May be useful for heart failure in patients who cannot take ACEI; do not inhibit bradykinin breakdown. • Renoprotective in diabetics. • Few side effects, and no cough.

40. Direct Renin Inhibitors (New- 2007 - IO) • Aliskeren (Tekturna)- Binds with and decreases plasma renin activity, blocking initiation of RAAS. • Similar to ACEI and ARB’s in lowering BP. Either monotherapy for mild HTN or added to other agents for mod/severe HTN. Dose: 150-300 md/d • Very few adverse effects; no cough or angioedema. Cost: $80+/month. IO- interest only

41. Calcium Channel Blockers • Act by peripheral vasodilation and other mechanisms (see below). • Effective in all demographic groups, and are preferable in blacks and the elderly. • Can be used with other agents but must be individualized. • Additional protection against stroke (ALLHAT). • All Calcium blockers are not alike.

42. Dihydropyridine Agents • Amlodipine, Nifedipine, others. • Significant vasodilation, reduction in SVR. • Fluid retention and reflex tachycardia occur (role of ß-blockers and diuretics). • Unlikely to cause heart failure and conduction problems (in vivo). • Must use long acting preparations. • 2nd or 3rd line agents in diabetics.

43. Diltiazem and Verapamil • In addition to vasodilation these drugs have negative inotropic, chronotropic and dromotropic (slow A-V conduction) effects. • Can exacerbate heart failure and cause SA and AV nodal dysfunction. • Also used as anti-anginals and in Rx of arrhythmias. • Diltiazem may be used very cautiously with ß-blockers, but avoid verapamil. • Long acting preparationsSR/XL forms .

44. Calcium Channel Blockers • Side effects: headaches, peripheral edema (Dihydropyridines), constipation (Verapamil), bradycardia (Verapamil and Diltiazem).

45. Adjunctive Agents-4th Line Agents • -receptor blockers • Central acting agents • Arteriolar dilators

46. Alpha Receptor Blockers • Prazosin, Terazosin, Doxazosin. • Post-synaptic alpha receptor blockers; relax smooth muscle, decrease SVR; tachyphylaxis common with prazosin. • Side effects: Postural hypotension and syncope following 1st dose; palpitations, headaches. • Favorable effects on lipids (HDL). • Used as an adjunct to other agents. • Useful in BPH.

47. Central Acting Agents • Methyldopa, Clonidine, Guanabenz • Stimulate CNS presynaptic alpha-2 receptors resulting in reduced efferent peripheral sympathetic flow. • Side effects include fatigue, impotence, dry mouth, postural hypotension. • Benefits: Compliance- Clonidine patches are effective for 7 days.

48. Arteriolar Dilators • Direct relaxation of smooth muscle. Decrease SVR. • Hydralazine, Minoxidil. • Reflex tachycardia, fluid retention. • Best used as 3rd/4th line therapy combined with -blockers and diuretics.

49. Guidelines for Treating HTN • Initial Rx: Thiazide diuretic with some exceptions; multiple agents often needed. • Look for associated co-morbid conditions: diabetes, HF, angina pectoris, post MI. • Consider cost, compliance, and side effects.

50. Guidelines for Treating HTN • Initiate low dose; follow up at 4-6 wk intervals (sooner if BP >160/100). • Titrate to moderate/high doses before adding a second agent. Exception is thiazides- low/mod dose is adequate. • Additional drug therapy would include addition of a ß-Blocker, ACEI or Ca-Blocker. • If initial avg BP >160/90, alternative approach is to start with combination Rx.