ΥΠΕΡΤΑΣΗ ΚΑΙ ΣΤΕΦΑΝΙΑΙΑ ΝΟΣΟΣ Ι.Ε.ΚΑΝΟΝΙΔΗΣ

ΥΠΕΡΤΑΣΗ ΚΑΙ ΣΤΕΦΑΝΙΑΙΑ ΝΟΣΟΣ Ι.Ε.ΚΑΝΟΝΙΔΗΣ

CAD: Statistics CAD is the largest killer of American males and females 13 million Americans have CAD 1.1 million MI s per year Every 26 seconds an American will suffer from a coronary event Every 60 seconds an American will die because of a coronary event 42% of those having a coronary event will die from it 350000 people die per year because of a coronary event in the Emergency Department before even being admitted to the hospital Death Rate in 2001: 177 in 100,000

CAD: Demographics and Statistics 84% of those who die from CAD are 65 or older Within 1 year of initial MI: 25% of men and 38% of women will die Within 8 years of initial MI: 50% of men and women under 65 will die An average of 11.5 years of life are lost due to an MI IMPORTANT: 50% of men and 64% of women who have died suddenly via CAD DID NOT HAVE ANY PREVIOUS SYMPTOMS Sudden Death: Those with a previous history of MI have a 5-6 times Sudden Death rate compared to the general population

Hypertension Hypertension( HTN) is the most common primary diagnosis in America. 35 million office visits are as the primary diagnosis of HTN. 50 million or more Americans have high BP. Worldwide prevalence estimates for HTN may be as much as 1 billion. 7.1 million deaths per year may be attributable to hypertension.

Ηypertension The estimated prevalence of hypertension in the United States in 2005 was : 35.3 million for men 38.3 million for women. Hypertension is more prevalent in black persons than in Hispanic and non-hispanic white persons. This prevalence is increasing. Data from 1988-1994 and 1999-2002 demonstrated an increased prevalence of hypertension in black individuals from 35.8% to 41.4%.

6 Hypertension: A Significant CV and Renal Disease Risk Factor Stroke CAD CHF LVH Renal disease Hypertension Peripheral vascular disease Morbidity Disability National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.

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8 Hypertension and CHD : (MRFIT) SBP versus DBP in Risk of CHD Mortality CHD Death Rate 100+ 90 99 80 89 75 79 Diastolic BP (mm Hg) 70 74 <70 <120 120 139 140 159 160+ Systolic BP (mm Hg) Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.

Biennial Age-Adjusted Rate per 1,000 9 Risk of Cardiovascular Events by Hypertensive Status 36-Year Follow-up in Patients Aged 35-64 Years 50 Coronary Disease Stroke Peripheral Arterial 45.4 Disease Cardiac Failure 40 30 20 10 0 Normotensive Hypertensive 22.7 21.3 12.4 13.9 9.5 9.9 6.2 7.3 5.0 6.3 3.3 2.4 3.5 2.0 2.1 Men Women Men Women Men Women Men Women Reprinted with permission from Kannel WB. JAMA. 1996;275:1571-1576.

10 Elevated SBP Alone Is Associated With Increased Risk of Cardiovascular and Renal Disease Disease Relative Risk Kidney failure (ESRD) 2.8 Stroke 2.7 Heart failure 1.5 Peripheral vascular disease 1.8 Myocardial infarction* =1.6 Coronary artery disease 1.5 ESRD = end-stage renal disease; SBP 165 mm Hg. *Men only. Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part 1):587-594; Klag MJ et al. N Engl J Med. 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger. 1996;158:3779-3783; Neaton JD et al. Arch Intern Med. 1992;152:56-64.

12 Benefits of Lowering BP Average Percent Reduction Stroke incidence 35 40% Myocardial infarction 20 25% Heart failure 50% TROPHY Study ACC 2006: Even lowering BP in those with pre-htn appears to reduce incidence of new HTN by up to 60%

INTERHEART study About 25% of the population-attributable risk of a myocardial infarction can be accounted for by hypertension

Pathophysiological Association of hypertension with IHD Atherogenesis Hypertrophy Endothelial dysfunction, which leads to the developement of atherosclerosis, Increased afterload leading to myocardial hypertrophy.

LVH The rate of LVH based on ECG findings 2.9% for men 1.5% for women. based on echocardiographic findings 15-20% 33% of patients without LVH have evidence of asymptomatic LV diastolicdysfunction.

ECG -Hypertension Electrocardiogram from a 46-year-old man with long-standing hypertension showing left atrial abnormality and left ventricular hypertrophy with strain.

17 Blood Pressure Classification BP Classification SBP mmhg DBP mmhg Normal <120 and <80 Prehypertension 120 139 or 80 89 Stage 1 HTN 140 159 or 90 99 Stage 2 HTN >160 or >100

BHS classification of blood pressure levels Category Systolic blood Diastolic blood pressure (mmhg) pressure Optimal blood pressure <120 <80 Normal blood pressure <130 <85 High-normal blood pressure 130-139 85-89 Grade 1 Hypertension (mild) 140-159 90-99 Grade 2 Hypertension (moderate) 160-179 100-109 Grade 3 Hypertension (severe) >180 >110 Isolated Systolic Hypertension (Grade 1) 140-159 <90 Isolated Systolic Hypertension (Grade 2) >160 <90

Total Cardiovascular risk in Hypertensive Patients

Treatment modalities in Hypertensive Patients

Non pharmacological Treatment of hypertension and lifestyle changes Lose weight, if overweight Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fats and cholesterol Increase consumption of fruits and vegetables Limit alcohol intake

Lifestyle Modification Modification Approximate SBP reduction (range) Weight reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption 5 20 mmhg / 10 kg weight loss 8 14 mmhg 2 8 mmhg 4 9 mmhg 2 4 mmhg

Drug therapy for hypertension Class of drug Example dose Initiating dose Usualmaintenance Diuretics Hydrochlorothiazide 12.5 mg o.d. 12.5-25 mg o.d. -blockers Atenolol 25-50 mg o.d. 50-100 mg o.d. Calcium Amlodipine 2.5-5 mg o.d. 5-10 mg o.d. channel blockers -blockers prazosin 2.5 mg o.d 2.5-10mg o.d. ACE- inhibitors ramipril 1.25-5 mg o.d. 5-20 mg o.d. Angiotensin-II Losartan 25-50 mg o.d. 50-100 mg o.d. receptor blockers

Pharmacological Treatment in Hypertension

J-Curve In favor Stewart Lancet 1979 Cruickshank et al Lancet 1987 Miller Hypertension 2000 Against Farnett et al JAMA 1991 McMahon et al Lancet 1990 J-Curve in HTN plus CAD INVEST TNT SMART

HOT Study: Significant Benefit From Intensive Treatment in the Diabetic Subgroup 25 20 Major cardiovascular events/1,000 patient-years 15 10 p=0.005 for trend 5 0 90 85 80 Target Diastolic Blood Pressure mm Hg Hansson L et al. Lancet. 1998;351:1755-1762.

Recommendations. In patients with an elevated DBP and CAD with evidence of myocardial ischemia, the BP should be lowered slowly, and caution is advised in inducing decreases in DBP to <60 mm Hg in any patient with diabetes mellitus or who is >60 years of age. In older hypertensive individuals with wide pulse pressures, lowering SBP may cause very low DBP values (<60 mm Hg). This should alert the clinician to assess carefully any untoward signs or symptoms, especially those resulting from myocardial ischemia (Class Iia;Level of Evidence: C).

Best BP CAMELOT ACCORD SPRINT

Recommendations 1. The <140/90-mm Hg BP target is reasonable for the secondary prevention of cardiovascular events in patients with hypertension and CAD (Class IIa; Level of Evidence: B). 2. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (carotid artery disease, PAD, abdominal aortic aneurysm) (Class IIb; Level of Evidence: B).

Treatment of BP in pts with IHD Treatment of BP in primary prevention of IHD Treatment of BP in secondary prevention of IHD Treatment of BP in established IHD Treatment of BP in ACS

ΕΠΙΛΟΓΗ ΑΝΤΙΥΠΕΡΤΑΣΙΚΩΝ ΦΑΡΜΑΚΩΝ ΣΤΗΝ ΠΡΩΤΟΓΕΝΝΗ ΠΡΟΛΗΨΗ ΣΤΕΦΑΝΙΑΙΑΣ ΝΟΣΟΥ Δεν υπάρχει διαφορά μεταξύ των διαφόρων κατηγοριών αντιυπερτασικών φαρμάκων στην πρωτογενή πρόληψη, όσον αφορά την επίπτωση της στεφανιαίας νόσου και των καρδιαγγειακών επιπλοκών γενικώτερα.

ΕΠΙΛΟΓΗ ΑΝΤΙΥΠΕΡΤΑΣΙΚΩΝ ΦΑΡΜΑΚΩΝ ΣΤΗΝ ΔΕΥΤΕΡΟΓΕΝΝΗ ΠΡΟΛΗΨΗ ΣΤΕΦΑΝΙΑΙΑΣ ΝΟΣΟΥ B-blockers ACE Inhibitors ARBBs Diuretics CCB

Diuretics in secondary prevention THIAZIDES Veterans Administration MRC SHEP HYVET Chlorothalidone ALLHAT

ARBs VALUE OPTIMAAL VALIANT TRANSCEND

ACE Inhibitors in secondary prevention HOPE EUROPA PEACE ONTARGET

CCB ALLHAT amlodipine VS diuretic or ACE ASCOT amlodipine VS b-blockers CONNICLE verapamil VS b-blockers or diuretic INVEST verapamil VS NORDIL diltiazem VS b-blockers or diuretic

Recommendations I 1. Patients with hypertension and chronic stable angina should be treated with a regimen that includes: a) b-blocker in patients with a history of prior MI b) An ACE inhibitor or ARB if there is prior MI, LV systolic dysfunction, diabetes mellitus, or CKD; and c) A thiazide or thiazide-like diuretic (Class I; Level of Evidence: A). 2. The combination of a b-blocker, an ACE inhibitor or ARB, and a thiazide or thiazide-like diuretic should also be considered in the absence of a prior MI, LV systolic dysfunction, diabetes mellitus, or proteinuric CKD (Class IIa; Level of Evidence: B). 3. If b-blockers are contraindicated or produce intolerable side effects, a nondihydropyridine CCB (such as diltiazem or verapamil) may be substituted, but not if there is LV dysfunction (Class IIa; Level of Evidence: B).

Recommendations II 4. If either the angina or the hypertension remains uncontrolled, a long-acting dihydropyridine CCB can be added to the basic regimen of b-blocker, ACE inhibitor, and thiazide or thiazide-like diuretic. The combination of a b-blocker and either of the nondihydropyridine CCBs (diltiazem or verapamil) should be used with caution in patients with symptomatic CAD and hypertension because of the increased risk of significant bradyarrhythmias and HF (Class IIa; Level of Evidence: B). 5. For patients with stable angina, the BP target is <140/ 90 mm Hg. (Class I; Level of Evidence: A) A lower target BP (<130/80 mm Hg) may be considered in some individuals with CAD, with previous stroke or transient ischemic attack, or with CAD risk equivalents (carotid artery disease, PAD, abdominal aortic aneurysm) (Class IIb; Level of Evidence: B)..

Antiplatelet or Anticoagulant drugs 6. There are no special contraindications in hypertensive patients for the use of antiplatelet or anticoagulant drugs, except that in patients with uncontrolled severe hypertension who are taking antiplatelet or anticoagulant drugs, the BP should be lowered without delay to reduce the risk of hemorrhagic stroke (Class IIa; Level of Evidence: C).

ΕΠΙΛΟΓΗ ΑΝΤΙΥΠΕΡΤΑΣΙΚΩΝ ΦΑΡΜΑΚΩΝ ΣΤΑ ΟΞΕΑ ΙΣΧΑΙΜΙΚΑ ΣΥΝΔΡΟΜΑ B-blockers ACE Inhibitors ARBBs Diuretics Nitates

ACE inhibitors in ACS GISSI 3 ISSIS 4 CCS 1 ACE inh post ACS

. Recommendations 1. If there is no contraindication to the use of b-blockers, in patients with ACS, the initial therapy of hypertension should include a short-acting b1-selective b-blocker without intrinsic sympathomimetic activity (metoprolol tartrate or bisoprolol). b-blocker therapy should typically be initiated orally within 24 hours of presentation (Class I; Level of Evidence: A). For patients with severe hypertension or ongoing ischemia, an intravenous b-blocker (esmolol) can be considered (Class IIa; Level of Evidence: B). For hemodynamically unstable patients or when decompensated HF exists, the initiation of b-blocker therapy should be delayed until stabilization has been achieved (Class I; Level of Evidence: A).

2. In patients with ACS and hypertension, nitratesshould be considered to lower BP or to relieve ongoing ischemia or pulmonary congestion (Class I; Level of Evidence: C). Nitrates should be avoided in patients with suspected right ventricular infarction and inthose with hemodynamic instability. Sublingual or intravenous nitroglycerin is preferred for initial therapy and can be transitioned later to a longeracting preparation if indicated.

3. If there is a contraindication to the use of a b-blocker or intolerable side effects, then a nondihydropyridine CCB such as verapamil or diltiazem may be substituted for patients with ongoing ischemia, provided that LV dysfunction or HF is not present. If the angina or hypertension is not controlled on a b-blocker alone, a longer-acting dihydropyridine CCB may be added after optimal use of an ACE inhibitor (Class IIa; Level of Evidence: B). 4. An ACE inhibitor (Class I; Level of Evidence: A) or an ARB (Class I; Level of Evidence: B) should be added if the patient has an anterior MI, if hypertension persists, if the patient has evidence of LV dysfunction or HF, or if the patient has diabetes mellitus. For lowerrisk ACS patients with preserved LV ejection fraction and no diabetes mellitus, ACE inhibitors can be considered a first-line agent for BP control (Class IIa; Level of Evidence: A).

5. Aldosterone antagonists are indicated for patients who are already receiving b- blockers and ACE inhibitors after MI and have LV dysfunction and either HF or diabetes mellitus. Serum potassium levels must be monitored. These agents should be avoided in patients with elevated serum creatinine levels ( 2.5 mg/dl in men, 2.0 mg/dl in women) or elevated potassium levels ( 5.0 meq/l) (Class I; Level of Evidence: A). 6. Loop diuretics are preferred over thiazide and thiazide-type diuretics for patients with ACS who have HF (NYHA class III or IV) or for patients with CKD and an estimated glomerular filtration rate <30 ml/min. For patients with persistent hypertension not controlled with a b-blocker, an ACE inhibitor, and an aldosterone antagonist, a thiazide or thiazide-type diuretic may be added in selected patients for BP control (Class I; Level of Evidence: B). 7. The target BP is <140/90 mm Hg in patients with ACS who are hemodynamically stable (Class IIa; Level ofevidence: C). A BP target of <130/80 mm Hg at the time of hospital discharge is a reasonable option (Class IIb;Level of Evidence: C). The BP should be lowered slowly, and caution is advised to avoid decreases in DBP to <60 mm Hg because this may reduce coronary perfusion and worsen ischemia.

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