Managing the Complicated Hypertensive Patient

Transcription

1 Managing the Complicated Hypertensive Patient Cheryl L. Laffer, MD, PhD, FAHA Associate Professor of Medicine, Texas A&M HSC College of Medicine Senior Staff, S&W Hypertension - Internal Medicine Vice President (Texas Chapter) and Specialist in Clinical Hypertension, American Society of Hypertension

2 Lifetime Risk of Developing Hypertension Beginning at Age Risk of hypertension (%) Men Years Women Framingham: people with blood pressure <140/90 mmhg at age 65 Vasan RS et al. JAMA. 2002; 287:1003

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4 Latest NHANES Data: p<0.05 for all prevalence, but first in # uncontrolled & average: 143/80 to 135/74 JAMA 2010;303:2043

5 NHANES: 45% of US adults have Hypertension, Dyslipidemia or Diabetes - Highest in Blacks NCHS Data Brief 2010;10:36

6 JNC7 Express: JAMA 2003;289:2534

7 JNC7 Blood Pressure Classification BP Classification SBP mmhg DBP mmhg Normal <120 and <80 Prehypertension or Stage or Stage 2 >160 or >100 JAMA 2003;289:2560

8 Office BP Measurement Use auscultatory method with a properly calibrated and validated instrument. Patient should be seated quietly for 5 minutes in a chair (not on the exam table), feet on the floor, arm supported at heart level. Appropriate-sized cuff should be used to ensure accuracy. At least two measurements should be made. Check in other arm (once), confirm at 1 month (unless Stage 2).

9 JNC-Recommended Initial Tests Routine Tests Electrocardiogram Urinalysis Blood count (hematocrit) Serum glucose, potassium, calcium and creatinine, or the corresponding estimated GFR, Lipid profile, after 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides Optional tests Measurement of urinary albumin excretion or albumin/creatinine ratio More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

10 JNC7 Hypertension Treatment Algorithm Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmhg) (<130/80 mmhg for those with diabetes or chronic kidney disease) Without Compelling Indications Initial Drug Choices With Compelling Indications Stage 1 Hypertension (SBP or DBP 90 99) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension (SBP >160 or DBP >100) 2-drug combination for most (usually thiazide-type diuretic+ ACEI, or ARB, or BB, or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. JNC7. JAMA 2003;289:2560

11 Efficacious Lifestyle Modification Salt sdmnf Salt abc Weight: 1 kg = 1.6/1.3 mmhg Achieve <15% above ideal Na intake: 100 meq = 5.4/6.5 mmhg SBP 8-14 mm: DASH diet mg Na Achieve 4-6 g salt/day ( meq Na) Shopping smart EtOH to 30 cc = 1 oz / day whiskey 3 oz, wine 10 oz, beer 24 oz; half in women Exercise aerobics 30 min 5-6 x / wk = 4-9 mm SBP

12 SBP-lowering with DASH diet + Na DASH: Sacks et al. NEJM 2001;344:3

13 Effect of DASH-Na Diet on Systolic / Age Sacks & Campos. NEJM 2010;362:2102

14 JNC7 Hypertension Treatment Algorithm Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmhg) (<130/80 mmhg for those with diabetes or chronic kidney disease) Without Compelling Indications Initial Drug Choices With Compelling Indications Stage 1 Hypertension (SBP or DBP 90 99) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension (SBP >160 or DBP >100) 2-drug combination for most (usually thiazide-type diuretic + ACEI / ARB / BB / CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. JNC7. JAMA 2003;289:2560

15 ALLHAT: Primary Endpoint and Subgroups Combined CHD deaths and nonfatal MI, Relative Risk (95% CI) Total 0.98 ( ) 0.99 ( ) Age < ( ) 0.95 ( ) Age ( ) 1.01 ( ) Men 0.98 ( ) 0.94 ( ) Women 0.99 ( ) 1.06 ( ) Black 1.01 ( ) 1.10 ( ) Nonblack 0.97 ( ) 0.94 ( ) Diabetic 0.99 ( ) 1.00 ( ) Nondiabetic 0.97 ( ) 0.99 ( ) Favors Amlodipine Favors Chlorthalidone Favors Lisinopril Favors Chlorthalidone JAMA 2002;288:

16 JNC7 Hypertension Treatment Algorithm Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmhg) (<130/80 mmhg for those with diabetes or chronic kidney disease) Without Compelling Indications Initial Drug Choices With Compelling Indications Stage 1 Hypertension (SBP or DBP 90 99) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension (SBP >160 or DBP >100) 2-drug combination for most (usually thiazide-type diuretic + ACEI, or ARB, or BB, or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. JNC7. JAMA 2003;289:2560

17 Compelling Indications for Individual Classes Compelling Indication Initial Therapy Options Clinical Trial Basis Heart failure THIAZ, BB, ACEI, ARB, ALDO ANT ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES Postmyocardial infarction High CAD risk BB, ACEI, ALDO ANT THIAZ, BB, ACE, CCB ACC/AHA Post-MI Guideline, BHAT, SAVE Capricorn, EPHESUS ALLHAT, HOPE, LIFE, ANBP2, CONVINCE JNC7. JAMA 2003;289:2560

18 Compelling Indications for Individual Compelling Indication Initial Therapy Options Clinical Trial Basis Diabetes Classes THIAZ, BB, ACEI, ARB, CCB NKF-ADA Guideline, UKPDS, ALLHAT Chronic Kidney Disease ACEI, ARB NKF-ADA Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK Recurrent Stroke Prevention THIAZ + ACEI PROGRESS JNC7. JAMA 2003;289:2560

19 JNC7 Hypertension Treatment Algorithm Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmhg) (<130/80 mmhg for those with diabetes or chronic kidney disease) Without Compelling Indications Initial Drug Choices With Compelling Indications Stage 1 Hypertension (SBP or DBP 90 99) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension (SBP >160 or DBP >100) 2-drug combination for most (usually thiazide-type diuretic + ACEI, or ARB, or BB, or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. It s on NextGen! JNC7. JAMA 2003;289:2560

20 Hypertension in High-Risk Patients: Number of Agents Needed UKPDS (<85 mm Hg, diastolic) MDRD (92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) RENAAL (<140/90 mm Hg) IDNT ( <135/85 mm Hg) 1 average 2 3 Number of BP Medications UKPDS=United Kingdom Prospective Diabetes Study; MDRD=Modification of Diet in Renal Disease; HOT=Hypertension Optimal Treatment; AASK=African American Study of Kidney Disease; RENAAL=Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; IDNT=Irbesartan Diabetic Nephropathy Trial. 4

21 (a brief reminder)

22 Sites of Action of Major Antihypertensive Drug Classes Diuretics -Blockers + Kidney tubules (Na/Ca) Calcium Channel / a 1 Blockers (vasodilators) Vascular smooth muscle Heart DRI ACEIs ARBs Kidney JGA Renin Angiotensin I Angiotensin II x x x AT 1 receptors Renin-Angio-Aldo System

23 Diuretics (Thiazide-like) Benefits Reduce CHD mortality CHF ( incidence & progression: ALLHAT) Additive effect with most other classes Isolated Systolic H (SHEP) Decrease nephrolithiasis and osteoporotic hip fractures Reversal of LVH Limitations NSAIDs / hi Na interfere Mg, K, Na [elderly] glucose & TChol+TG (short-term: TOMHS) ±ED Ca & uric acid (usually asymptomatic, but both sustained) All worse with HCTZ>50 or chlorthalidone>25 mg daily JNC7. JAMA 2003;289:2560

24 Patients With Hypertension Are Likely to Be Treated With NSAIDs Up to 36% (18 million) of adults with hypertension also have osteoarthritis 1 12 million patients receiving NSAIDs for treatment of osteoarthritis are also being treated with antihypertensive medication 2 NSAID use is highest in the elderly, the segment of the population with the highest prevalence of hypertension 2 In addition to their effects on salt, they increase daily production of ET-1 by 83% 1. Blake. Am Fam Physician. 1994;50:138, 2. Ruoff. Clin Ther. 1998;20:376, 3. Johnson. J Hum Hypertens 1996;10:257

25 Incidence of Clinically Meaningful BP Elevation with COX-II inhibitors Study 1 1 Study 2 2 Celecoxib 200 mg qd (n=411) (n=549) Study 1 1 Study 2 2 Rofecoxib 25 mg qd (n=399) (n=543) Percentage of Patients p=0.03 p< SBP >20 mm Hg and >140 mm Hg ns ns DBP >15 mm Hg and >90 mm Hg 1.Whelton et al. Am J Ther 2001;8:85, 2.Data on file, Pfizer

26 Sites of Action of Major Antihypertensive Drug Classes Diuretics -Blockers + Kidney tubules Calcium Channel / a 1 Blockers (vasodilators) Vascular smooth muscle Heart DRI ACEIs ARBs Kidney JGA Renin Angiotensin I Angiotensin II x x x AT 1 receptors Renin-Angio-Aldo System

27 Beta - Blockers Benefits Anti-anginal Post-MI prophylaxis (secondary prevention) LV systolic dysfunction Reversal of LVH, but less than other classes Combined ab blockers (labetalol / carvedilol) appear to benefit without limitations Limitations Lipids: HDL TG Worsen insulin resistance [not ab: GEMINI] Asthma (bronchospasm with less b1-selective - caution in COPD) PAD / ED / >1 AVB Exercise-intolerance Down-titrate Benowitz 1995; JNC7 2003

28 -Blockers and Clinical Outcomes Relative Risk Other antihypertensives All -blockers Placebo All-Cause Mortality Stroke Myocardial Infarction All-Cause Mortality Lindholm et al. Lancet 2005;366:1545

29 Should beta-blockers remain first-line therapy? 2006: UK (NICE: National Institute for health & Clinical Excellence) removes them as 1/2/3 rd -line Rx of uncomplicated hypertension (ASCOT, LIFE, etc.) NICE recommends thiazide or CCB as first line in most (older, blacks, ) otherwise ACE-inhibitor European guideline updates in 2007 & 09 did not concur, latest emphasizes individualized Rx What will happen in JNC8?

30 Sites of Action of Major Antihypertensive Drug Classes Diuretics -Blockers + Kidney tubules Calcium Channel / a 1 Blockers (vasodilators) Vascular smooth muscle Heart DRI ACEIs ARBs Kidney JGA Renin Angiotensin I Angiotensin II x x x AT 1 receptors Renin-Angio-Aldo System

31 ACE-Inhibitors / ARBs (DRI) Benefits Systolic CHF post-mi Improve insulin sensitivity [Micardis: PPARg agonist] Protect / prevent (non/&) diabetic nephropathy Stroke prevention (losartan vs atenolol - LIFE trial) Reversal of LVH (best?) No adverse lipid effects Limitations ACEIs: angioedema / cough hypotension: with volume depletion [don t STOP] Hyperkalemia (CKD / NSAIDs / Diab RTA4) Pregnancy (second-trim: to aldomet / labetalol) Bilat renal artery stenosis Benowitz 1995; JNC7 2003

32 Sites of Action of Major Antihypertensive Drug Classes Diuretics -Blockers + Kidney tubules Calcium Channel / a 1 Blockers (vasodilators) Vascular smooth muscle Heart DRI ACEIs ARBs Kidney JGA Renin Angiotensin I Angiotensin II x x x AT 1 receptors Renin-Angio-Aldo System

33 Calcium-Channel Blockers Benefits Anti-anginal Isolated Systolic Htn (DHP: CVA & mortality: Syst-Eur) Work in low-renin states Neutral lipids / DM Reversal of LVH Limitations Short-acting may - mortality* Constipation (V/D) / tachycardia, flushing, edema (DHP) Caution with CHF JNC7 2003; *Furberg Am J Hypertens 1996;9:122

34 Alpha-1 Blockers Benefits Lipids: HDL LDL TG net: Chol/HDL - unique Improve insulin sensitivity Relaxation of bladder sphincter (BPH) Reversal of LVH No reduction in C.O. No adverse renal / pulmonary effects Limitations First-dose effect: orthostatic hypotension (visceral pooling) - initiate h.s. Worsening of stress urinary incontinence (elderly F) Rare exacerbation of angina (small vessel constriction) Nasal stuffiness CHF (vs chlorthalidone ALLHAT)

35 Fourth Line

36 Centrally-Acting Alpha 2 Agonists CLONIDINE GUANABENZ / GUANFACINE Brainstem stimulation: a 2 receptors + imidazole receptors (clonidine) Peripheral stimulation: a 1 and presyn a 2 receptors SNS Activity Vagal Tone HR Norepinephrine Renin release NET: TPR+ CO = BP Acute withdrawal associated with BP rebound at moderate doses Side effects (diminish with time): dry mouth, drowsy, dizzy, constipated, sedated

37 When all else fails: Direct Vasodilators, but VASODILATOR DIURETIC Vasodilation Peripheral Resistance Arterial Pressure Sodium Retention Renin Release Fluid Volume Angiotensin Aldosterone Vasoconstriction SYMPATHETIC BLOCKER SNS Activity Norepinephrine Heart Rate & Contractility Venous Compliance Cardiac Output TPR MINOXIDIL: vsm K-channel opener (±) hair growth, rare pericardial effusion HYDRALAZINE resistance artery vasorelaxant (-) lupus-like reaction, vasculitis Koch-Weser. Arch Intern Med 1974;133:1017

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39 Renin Profiling: U Na V and PRA PRA (nga I /ml/hr) % below lower 95% CI UNaV (meq/24 hrs) Laffer CL, Elijovich F. J Clin Hypertens 2002;4:266

40 Effects of Different Antihypertensives on BP of Caribbean Hispanic Subjects Systolic BP (mmhg) Diastolic BP (mmhg) * * * Placebo, n=14 ACE Inh, n=24 Ca ++ Blocker, n=10 bblocker, n=13 HCTZ, n=18 *, : significant vs placebo * * * HCTZ+ACE Inh, n=13 HCTZ+bBlocker, n=14 Laffer & Elijovich. J Clin Hypertens 2002;4:266

41 Salt-Sensitivity of BP Definition: BP from high-to-low or BP from low-to-high Na intake (slow dietary or rapid iv) AA hypertensive 75-80% White hypertensive 55-60% All normotensive 35%

42 Prognosis of SS in humans Kaplan-Meier curves for normotensive (N) or hypertensive (H) subjects, either salt-sensitive (S) or resistant (R) Weinberger et al. Hypertension 2001;37:429

43 Projected effects of Dietary Salt Reduction on Future Cardiovascular Disease Reducing dietary salt by 3 gm (1200 mg Na) would reduce annual new cases of: CHD by ,000, stroke by 32-66,000 and MI by 54-99,000; with overall decrease in deaths from any cause by 44-92,000. Higher risk groups benefit more: Blacks in all, Women in stroke, Older in CHD, Younger in mortality reductions. Overall annual savings of ,000 QALYs and $10 $24,000,000,000 (BILLIONS!) in US healthcare costs Bibbins-Domingo et al. NEJM 2010;362:590

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45 Renin Profiling, Clinical Correlates and Selection of Therapy High PRA (15-18%) Normal (50-55%) Low (30-35%) Young Middle-aged Old Fair Skinned Darker Skinned Sympathetic Activity Obesity / Diabetes Diuretics -blockers Calcium blockers ACE-inhibitors a1 antagonists AngII-receptor DRI?

46 Resistant Hypertension Defined as BP not at goal despite good doses of three different (classes of) drugs, one of which is a diuretic. More common in elderly, obese, salt-lovers, diabetics, those with CKD or LVH More frequent in women than men, blacks than whites, southeast [ stroke belt ] Rule out extrinsic causes / noncompliance / white coat [ABPM or home BP <135/85] AHA statement. Hypertension 2008;51:1503

47 Extrinsic Hyperadrenergic Syndromes Disorder Mechanism Comments Amphetamines Direct + Catechol Release Appetite Suppressant, Illicit OTC Diet Pills Direct Adrenergic 2-fold Dose Produces HTN MAO Inh/Tyramine Massive Catechol Release In Psychiatric Patients Cocaine Inhibit Catechol Reuptake Tox Screen Clonidine Rebound Activation Central SNS Non-Compliance Panic Disorder Activation Central SNS Hx Required for Dx

48 Other Drugs / Agents that Raise Blood Pressure NSAIDS [kidney transporter, Na - PGE2/I2] Oral contraceptives [minor, increase AoGT] Alcohol > 4 (men) / 2 (women) drinks per day Corticosteroids [aldosterone effect] Erythropoietin [interferes with NO - add nitrate] Black licorice [snuff / chewing tobacco] Herbals [ma huang / ephedra, e.g., Metabolife]

49 Secondary Causes of (R) Hypertension Sleep Apnea [snoring / witnessed apnea / daytime sleepiness] refer for sleep study Intrinsic renal disease [ egfr, abnormal UA, etc] should be seen by Nephrologist Hyperaldosteronism [unexpected low K, hi CO2] screen with aldo:pra (specific only) Renal artery stenosis [bruit anywhere, PAD or CAD] MRA / renal Doppler / CT angiogram

50 RARE Causes of (R) Hypertension Pheochromocytoma [paroxysms / pale sweat / piloerection] pl metanephrines / clonidine test Cushing s disease [moon facies, etc] screening cortisol, dexamethasone-suppression test Hyperparathyroidism [hi Ca] screen with good ipth assay Aortic coarctation [DBP >10 between arms / leg] MRA / CT angiogram Intracranial tumor

51 Conclusions for Hypertension in Primary Care Most essential hypertensives are saltsensitive All patients with essential hypertension must be advised to reduce salt intake No essential hypertensive patient should be diagnosed as resistant if there is no diuretic in the treatment regimen If you can t control it, refer (HTN,, )