An Epidemiological Overview

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2 An Epidemiological Overview Cardiovascular disease (CVD) is the leading cause of death in the U.S. In 2005 CVD accounted for approximately 38 percent of all deaths CVD has been the number one killer in the U.S. since 1900 except for 1918 (influenza) More that 2,500 Americans die from CVD each day Among women, 1 in 2.6 deaths from CVD

3 Death Rates for Cardiovascular Disease, Including CHD and Stroke for Selected Countries

Inactivity Blood Sugar Blood Pressure Cholesterol BMI Heart Disease Stroke Cancer Chronic Lung Ds Predisposing

4 Increasing Prevalence of the Risk Factors for Non Communicable Diseases Globalization Urbanization Poverty Low Education Stress Smoking Unhealthy Diet Phys. Inactivity Blood Sugar Blood Pressure Cholesterol BMI Heart Disease Stroke Cancer Chronic Lung Ds Predisposing Environment Behavioral Risk Factors Biologic Risk factors Chronic NCD Morbidity/Mortality Adopted Preventing Chronic Disease: A Vital Investment. WHO 2005 Lancet 2011; 337:

5 Understanding The Cardiovascular System Figure 15.4

6 Types Of Cardiovascular Disease Atherosclerosis Coronary heart disease (CHD) Chest pain (angina pectoris) Irregular heartbeat (arrhythmia) Congestive heart failure (CHF) Congenital and rheumatic heart disease Stroke

7 Percentage Breakdown of Deaths from Cardiovascular Disease in the United States, 2001

8 Atherosclerosis Characterized by deposits of fatty substances, cholesterol, cellular waste products, calcium, and fibrin in the inner lining of the artery Hyperlipidemia abnormally high blood lipid level Plaque the buildup of deposits in the arteries

Prevention of Cardiovascular Disease is anchored on preventing or slowing the progression of atherosclerosis Foam Cells Fatty Streak Intermediate Lesion Atheroma Fibrous Plaque Complicated

9 Prevention of Cardiovascular Disease is anchored on preventing or slowing the progression of atherosclerosis Foam Cells Fatty Streak Intermediate Lesion Atheroma Fibrous Plaque Complicated Lesion/Rupture Stroke TIA MI Angina High BP Renal failure Endothelial Dysfunction PAD From First Decade From Third Decade From Fourth Decade Growth Mainly by Lipid Accumulation Smooth Muscle and Collagen Thrombosis Hematoma Pepine CJ. Am J Cardiol. 1998;82:23S-27S.

10 Atherosclerosis is a clinically SILENT process Genetic Environmental Clinical Events Age (yrs)

11 Atherosclerosis often first manifests catastrophically

12 Coronary Heart Disease Myocardial infarction (MI) or heart attack blood supplying the heart is disrupted Coronary thrombosis blood clot in the artery Embolus when the blood clot is dislodged and moves through the circulatory system Collateral circulation - if blockage to the heart is total, an alternative blood flow is selected

13 Angina Pectoris Ischemia reduction of the heart s blood and oxygen supply The more serious the oxygen deprivation the more severe the pain Nitroglycerin drug used to relax (dilate) the veins Beta blockers control potential overactivity of the heart muscle

14 Arrhythmias An irregularity in heart rhythm Tachycardia racing heart in the absence of exercise or anxiety Bradycardia abnormally slow heartbeat Fibrillation heart beat is sporadic, quivering pattern

15 Congestive Heart Failure (CHF) Damaged or overworked heart muscle is unable to keep blood circulating normally Affects over 5 million Americans Damage to heart muscle may result from: rheumatic fever, pneumonia, heart attack, or other cardiovascular problem Lack of proper circulation may allow blood to accumulate in the vessels of the legs, ankles, or lungs Diuretics relieve fluid accumulation

16 Congenital And Rheumatic Heart Disease Congenital heart disease affects 1 out of 125 children born May be due to hereditary factors, maternal diseases, or chemical intake (alcohol) during fetal development Rheumatic heart disease results from rheumatic fever which affects connective tissue

17 Stroke Occurs when the blood supply to the brain is interrupted Thrombus blood clot Embolus free flowing clot Aneurysm bulging or burst blood vessel Transient ischemic attack (TIA) brief interruptions that cause temporary impairment

18 Common Blood Vessel Disorders

19 Women And Cardiovascular Disease 2003, CVD deaths 426,800 men 483,800 women Estrogen Once estrogen production stops, risk for CVD death increases Diagnostic and therapeutic differences Delay in diagnosing possible heart attack Complexity in interpreting chest pain in women Less aggressive treatment of female heart attack victims Smaller coronary arteries in women Gender bias in CVD research typically CVD research has been conducted on male subjects

20 Reducing Your Risk For Cardiovascular Diseases Risks you CAN control Avoid tobacco Maintain a healthy weight Modify dietary habits Exercise regularly Control diabetes Control blood pressure Systolic Diastolic Control lipid Cut back on saturated fat and cholesterol Manage stress

21 Reducing Your Risk For Cardiovascular Diseases Risks you CANNOT control Heredity Age Gender Race

22 What is arterial hypertension? High blood pressure (hypertension) is a common condition in which the force of the blood against your artery walls is high enough that it may eventually cause health problems, such as heart disease. Blood pressure is determined by the amount of blood your heart pumps and the amount of resistance to blood flow in your arteries. The more blood your heart pumps and the narrower your arteries, the higher your blood pressure. High blood pressure generally develops over many years. Usually patients have high blood pressure (hypertension) for years without any symptoms. Even without symptoms, damage to blood vessels and your heart continues and can be detected. Uncontrolled high blood pressure increases your risk of serious health problems, including heart attack and stroke.

23 Hypertension is the leading cause of death globally, especially in Asia Ezzati and Riboli. N Engl J Med 2013;369: Deaths attributable to individual risk factors

24 Much of CV Mortality in Asia-Pacific Region Is Attributable to Hypertension IHD Hemorrhagic stroke Ischemic stroke Fiji Men Fiji Women Bangladesh Bangladesh Indonesia Indonesia Singapore Singapore Taiwan Taiwan Thailand Thailand Philippines Philippines China China Hong Kong Hong Kong South Korea South Korea Australia Australia New Zealand New Zealand Malaysia Malaysia Japan Japan Mongolia Mongolia Population-attributable fraction of CV deaths (%) due to hypertension in men (left) and women (right). IHD, ischemic heart disease. Martiniuk AL et al. J Hypertens. 2007;25(1):73-79.

25 Physiology of Hypertension 3 key physiological mechanism lead to development of hypertension 1. Sodium/Volume 2. Renin Angiotensin Aldosterone System (RAAS) 3. Sympathetic Nervous System (SNS) Studies prove that drugs targeting Sodium/Volume (CCBs and DU) or the RAAS system fare better than SNS blockers in CV outcomes and BP control Even though SNS tone is higher in hypertensive than in normotensives, these results indicates that in most cases the SNS is not a driving force The Journal of Clinical Hypertension 2012;14 (10 );

26 Multiple Interactions among the Mechanisms of Controlling Blood Pressure Kaplan and Opie. Lancet 2006;367:168 76

Evolution of Hypertension Younger Pre-hypertensive Hypertensive + Damage Vasoconstriction Increased Peripheral Resistance Vascular remodelling RAAS and SNS Activation

27 Evolution of Hypertension Younger Pre-hypertensive Hypertensive + Damage Vasoconstriction Increased Peripheral Resistance Vascular remodelling RAAS and SNS Activation Older Hypertensive + Clinical Disease Declining GFR Sodium retention Increased Cardiac output Stiff Aorta systolic hypertension Number of Drugs Plasma Renin B. Williams. 2007

Most Hypertensive Patients Have Additional Risk Factors REACH Registry N=67,888 patients aged 45 years or older from 44 countries 81.8% Hypertension a 90.3% with 3 RFs a 140/90 mm Hg at baseline.

28 Most Hypertensive Patients Have Additional Risk Factors REACH Registry N=67,888 patients aged 45 years or older from 44 countries 81.8% Hypertension a 90.3% with 3 RFs a 140/90 mm Hg at baseline. RFs include: treated diabetes, diabetic nephropathy, ankle-brachial index of <0.9, asymptomatic carotid stenosis 70%, SBP >150 mm Hg, treated hypercholesterolemia, current smoking, men 65 y, women 70 y. REACH, Reduction of Atherothrombosis for Continued Health; RF, risk factor; SBP, systolic blood pressure. Bhatt DL et al. JAMA. 2006;295(2):

29 Risk factors lead to increasing risk of organ damage and clinical events: The cardio-renal continuum The risk associated with hypertension is greatly magnified by other CV risk factors, e.g.: Hyperlipidemia Diabetes LVH Increased arterial stiffness The presence of such risk factors initiates pathological events and processes like oxidative stress and endothelial dysfunction which ultimately lead to overt organ damage and failure Many of these processes leading to CV and renal disease involve the renin-angiotensin system (RAS) and the actions of its most biologically active component angiotensin II Dzau et al. Circulation 2006;114: Mancia et al. J Hypertens 2007;25:

From risk factors to organ failure: A continuous

Damage LVH IMT Angina TIA Cardiovascular Event

Renal Disease Stroke End Organ Failure Mild Renal

Disease Chronic Heart Failure Hypertension Increased LDL

30 From risk factors to organ failure: A continuous development Clinical Disease Diabetes Subclinical Organ Damage LVH IMT Angina TIA Cardiovascular Event Proteinuria Myocardial Infarction Risk Factors Moderate Renal Disease Stroke End Organ Failure Mild Renal Disease LV remodeling Microalbuminuria End-Stage Renal Disease Chronic Heart Failure Hypertension Increased LDL Diabetes/Metabolic Syndrome Smoking Dzau VJ, et al. Circulation. 2006;114:

31 Diagnosis of Hypertension Office BP is recommended for screening and diagnosis of hypertension Diagnosis of hypertension should be based on at least two BP measurements per visit and on at least two visits Out-of-office BP should be considered to confirm the diagnosis of hypertension, identify the type of hypertension, detect hypotensive episodes, and maximize prediction of CV risk For out-of-office BP measurements, ABPM or HBPM may be considered, depending on indication, availability, ease, cost of use, and, if appropriate, patient preference Mancia G et al. J Hypertens. 2013;31(7):

32 Hypertension - JNC BP Classifications: SBP 220 Stage SBP (mm Hg) No recommendations for SBP in JNC I or JNC II ISH Borderline ISH Borderline Normal Stage 3 Stage 3 Stage 2 Stage 2 Stage 1 Stage 1 Highnormal Highnormal Normal Normal Optimal Optimal Stage 2 Stage 1 Prehypertension Normal JNC I JNC II JNC III JNC IV JNC V JNC VI JNC 7 JNC 8 JNC I. JAMA. 1977;237: JNC II. Arch Intern Med. 1980;140: JNC III. Arch Intern Med. 1984;144: JNC IV. Arch Intern Med. 1988;148: JNC V. Arch Intern Med. 1993;153: JNC VI. Arch Intern Med. 1997;157: Chobanian AV et al. JAMA. 2003;289:

33 Hypertension - JNC BP Classifications: DBP Stage 4 DBP (mm Hg) Hypertensive Severe Severe Severe Moderate Moderate Moderate Stage 3 Stage 3 Stage 2 Stage 2 Stage Consider therapy Mild Mild Mild Stage 1 Stage 1 Stage Highnormal Highnormal Highnormal Highnormal Normal Normal Normal Normal Optimal Optimal JNC I JNC II JNC III JNC IV JNC V JNC VI Prehypertension Normal JNC 7 JNC 8 JNC I. JAMA. 1977;237: JNC II. Arch Intern Med. 1980;140: JNC III. Arch Intern Med. 1984;144: JNC IV. Arch Intern Med. 1988;148: JNC V. Arch Intern Med. 1993;153: JNC VI. Arch Intern Med. 1997;157: Chobanian AV et al. JAMA. 2003;289:

34 What is Blood Pressure Variability (BPV)? BP normally fluctuates during the day and can vary from day to day in response to environmental challenges eg, stress, activity, carrying out tasks SBP Blood pressure (mmhg) Blood pressure (mmhg) DBP Higher mean BP overall Weeks Weeks Patient 1 with lower BPV Patient 2 with higher BPV 1. Schillaci G, et al. Hypertension 2011;58: Rothwell PM. Lancet 2010;375: BP, blood pressure; BPV, BP variability.

35 Increased 24-hour BPV has been associated with CV risk Incidence of mortality and cardiovascular events by fifths of the distributions of the systolic average real variability in 8,938 patients Hansen TW, et al. Hypertension 2010;55: BPV, blood pressure variability; CV, cardiovascular; NCV, non CV.

36 Guidelines on BPV NICE Variability in SBP when measured visit-to-visit is a strong predictor of stroke, independent of mean SBP Whatever the underlying mechanisms, SBP variability appears to be an important independent predictor of clinical outcomes Updated guidance recommends the best available evidence-based treatment options to suppress BPV in people with hypertension ESC/ESH guidelines Consideration should be given to the evidence that visit-to-visit BPV may be a determinant of CV risk, independently of the mean BP levels achieved during long-term treatment, and that, thus, CV protection may be greater in patients with consistent BP control throughout visits BP, blood pressure; CV, cardiovascular; BPV, BP variability; SBP, systolic BP. 1. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 127. Available at: 2. Mancia G, et al. Eur Heart J 2013;34:

37 Association between CV events and early morning period 18:00 0:00 6:00 12:00 Time of day 1. Muller JE, et al. N Engl J Med 1985;313: Marler JR, et al. Stroke 1989;20: CV, cardiovascular risk; EMBPS, early morning blood pressure surge.

38 Morning Blood Pressure surge: What is it? Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91. Patients with sleep-trough surge of >55 mm Hg were classified in the MBP surge group MBP, morning blood pressure.

39 MBP surge as a cardiovascular risk Morning surge group (n=46) Non-surge group (n=145) P-value Age (years) NS 24-h systolic BP (mmhg) NS Baseline data Silent cerebral infarct prevalence (%) Number (/person) Multiple cerebral infarcts prevalence (%) Prospective data Stroke incidence (%) (relative risk = 2.7) A 10 mm Hg increase in morning surge in SBP increased clinical stroke risk by 22% Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91. MBP, morning blood pressure; SBP, systolic blood pressure.

BPV and MBP surge are very important and should be targeted Therefore the class of antihypertensive which can control BPV and MBP surge should be the initial treatment of choice Which

40 BPV and MBP surge are very important and should be targeted Therefore the class of antihypertensive which can control BPV and MBP surge should be the initial treatment of choice Which class of antihyperintensives? CCB, ARB, ACEI, diuretics ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BPV, BP variability; CCB, calcium channel blocker.

41 Stratification of Total CV Risk Into Risk Categories According to BP, Risk Factors, and Comorbidities 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension BP, mmhg Other Risk Factors, Asymptomatic OD, or Disease High Normal SBP or DBP Grade 1 Hypertension SBP or DBP Grade 2 Hypertension SBP or DBP Grade 3 Hypertension SBP 180 or DBP 110 No other RF Low risk Moderate risk High risk 1 or 2 RFs Low risk Moderate risk Moderate to high risk High risk 3 RFs Low to moderate risk Moderate to high risk High risk High risk OD, CKD stage 3, or diabetes Moderate to high risk High risk High risk High to very high risk Symptomatic CVD, CKD stage 4, or diabetes with OD/RFs Very high risk Very high risk Very high risk Very high risk CKD, chronic kidney disease; CVD, cardiovascular disease; OD, organ damage. Mancia G et al. J Hypertens. 2013;31(7):

JNC 8 Guideline Treatment Recommendations and BP Goals Adult aged 18 years with hypertension Implement lifestyle interventions (continue throughout management) Set BP goal and initiate BP-lowering

42 JNC 8 Guideline Treatment Recommendations and BP Goals Adult aged 18 years with hypertension Implement lifestyle interventions (continue throughout management) Set BP goal and initiate BP-lowering medication based on age, diabetes, and CKD General population (no diabetes or CKD) Diabetes or CKD present Age 60 y Age <60 y All ages Diabetes present No CKD All ages CKD present with or without diabetes BP goal SBP <150 mm Hg DBP <90 mm Hg BP goal SBP <140 mm Hg DBP <90 mm Hg BP goal SBP <140 mm Hg DBP <90 mm Hg BP goal SBP <140 mm Hg DBP <90 mm Hg Nonblack Black All races Initiate thiazide-type diuretic or ACEI or ARB or CCB alone or in combination a Initiate thiazide-type diuretic or CCB alone or in combination Initiate ACEI or ARB, alone or in combination with other drug class Select a drug treatment titration strategy A. Maximize first medication before adding second or B. Add second medication before reaching maximum dose of first medication or C. Start with 2 medication classes separately or as FDC FDC, fixed-dose combination; a ACEIs and ARBs should not be used in combination James PA et al. JAMA. 2014;311(5):

2013 ESH/ESC Hypertension Guidelines ESH/ESC Hypertension Guidelines: Possible

useful (with some limitations) Man Black/dashed: possible but less well tested

(except for verapamil or diltiazem for rate control in AF).

43 2013 ESH/ESC Hypertension Guidelines ESH/ESC Hypertension Guidelines: Possible Combinations of Antihypertensive Drug Classes Green/continuous: preferred Green/dashed: useful (with some limitations) Man Black/dashed: possible but less well tested Red/continuous: not recommended Only dihydropyridines to be combined with β-blockers (except for verapamil or diltiazem for rate control in AF). Thiazides + β-blockers increase risk of new onset DM. ACEI + ARB combination is discouraged. Mancia G et al. J Hypertens. 2013;31(7):

44 Different Classes of Drugs have Different Sites of Action BP = Cardiac output = X Total peripheral resistance Heart rate X Stroke volume Arterial pressure Venous pressure β-blockers Diuretics CCBs ARBs ACEIs ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin Type II receptor blocker; CCB = calcium channel blocker Different, but complementary mechanism of action Beevers, et al. BMJ 2001;322:912 6; McGhee, et al. Crit Care Nurse 2002;22:60 4; Goodman & Gilman s Pharmacological Basis of Therapeutics. 9 th ed

45 New Weapons Against Heart Disease Techniques for diagnosing heart disease Electrocardiogram (ECG) Angiography Positron emission tomography (PET) Single positron emission color tomography (SPECT) Radionuclide imaging Magnetic resonance imaging (MRI) Ultrafast CT Digital cardiac angiography (DSA)

46 Angioplasty Versus Bypass Surgery Angioplasty a thin catheter is threaded through the blocked arteries. The catheter has a balloon on the tip which is inflated to flatten the fatty deposits against the wall of the artery Coronary bypass surgery a blood vessel is taken from another site and implanted to bypass blocked arteries and transport blood

47 Aspirin For Heart Disease? Research shows that 80 milligrams of aspirin every other day is beneficial to heart patients due to its blood thinning properties Some side effects of aspirin: gastrointestinal intolerance and a tendency for difficulty with blood clotting Should only be taken under the advice of your physician

48 Thrombolysis If victim reaches an emergency room and is diagnosed quickly, thrombolysis can be performed Thrombolysis involves injecting an agent such as tissue plasminogen activator (TPA) to dissolve the clot and restore some blood flow

49 Summary CV diseases are the leading cause of deaths globally There are numbers of risk factors that can be controlled to prevent CV diseases Hypertension is one of the important risk factor which could be managed Blood Pressure Variability and Morning BP Surge are associated with CV risk

An Epidemiological Overview

An Epidemiological Overview Cardiovascular disease (CVD) is the leading cause of death in the U.S. In 2005 CVD accounted for approximately 38 percent of all deaths CVD has been the number one killer in