1. HYPERTENSION Background for understanding the Hypertension literature. Jeffrey J. Kaufhold, MD Nephrology

2. HYPERTENSION SUMMARY l Background for understanding the literature of Hypertension l Review of Joint National Commission Recommendations (VII) 2003 l Clinical Evaluation and Case history.

3. Nat ’ l Health & Nutrition Exam Survey NHANES JNC 7 Dec 2003

4. Why do we treat Hypertension? What target for Systolic? What target for Diastolic? Which drugs to use? What complications to watch out for?

5. Hypertension Literature Summary l Malignant Hypertension - 1958 Kincaid-Smith and others DBP > 130 l used “old” drugs like Guanabenz, Hydralazine l Showed that attempt to treat was enough to significantly reduce mortality from stroke, heart failure, renal failure.

6. Hypertension Literature Summary l VA Cooperative Studies - 1967 DBP 115-129 mm Hg - 1970 DBP 90 -114 mm Hg l Used the new drug Inderal, hydralazine, Chlorthaladone l Demonstrated that reducing DBP below 90 significantly reduced mortality from Stroke, Heart failure and renal failure

7. HYPERTENSION Literature Summary l US Public Health Service 1977 Prospective placebo controlled trial for DBP 90-115 mm Hg l HDFP 1979 Introduced concept of Stepped Care l Oslo Study 1980 Treatment of Mild Hypertension l Medical Research Clinics (MRC) 1985 Single blind and community based.

8. HYPERTENSION Literature Summary l HDFP 1979 Introduced concept of Stepped Care l step 1 : B-blocker l Step 2 : Diuretic l Step 3 : Hydralazine l Step 4 : Clonidine or aldomet l Step 5 : Minoxidil

9. HYPERTENSION PARALLEL WORK l 1948 to 1972 Framingham Study l 1982 MRFIT l 1984 LRC (Lipid Research Clinics)

10. HYPERTENSION PARALLEL WORK l 1948 to 1972 Framingham Study 20 year follow-up on 5000 pts l Picked Framingham Mass as the town had low turnover l Observational study that defined the risk factors for heart disease l Did not look at treatment and cannot be used to guide treatment

11. HYPERTENSION PARALLEL WORK l 1982 MRFIT Multiple Risk Factor Intervention Trial l Randomized primary prevention trial Lower than expected rate of mortality in controls led to NS reduction. l The Usual care group showed a “study effect” as a result of publication of VA and other study results l Used by drug detailers to make the claim that older drugs like B-blockers and diuretics might raise mortality due to their effects on lipids – not supported by the data.

12. HYPERTENSION PARALLEL WORK l 1984 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected. l Due to increased suicide, homicide and Motor Vehicle accidents in the study group. l Interesting to note that in studies of rats on low cholesterol diet, the incidence of violent behavior increases.

13. HYPERTENSION PARALLEL WORK l 1948 to 1972 Framingham Study 20 year follow-up on 5000 pts l 1982 MRFIT Randomized primary prevention trial Lower than expected rate of mortality in controls led to NS reduction. l 1984 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

14. HYPERTENSION Recent Works l 1985 HDFP follow-up Study Long term surveillence for drug side effects: 9-25 % l 1993 VA Cooperative Study, Materson, NEJM Compares 6 agents. Efficacy in 55 % range. Drug intolerance 6 to 14 %. l No significant difference in control between drug classes l No significant benefit by drug class between races l No significant difference in side effect risk

15. HYPERTENSION Recent Works l 1992 Gurwitz Ann Int Med Antihypertensive therapy and the initiation of Treatment for Diabetes. l Looked at link between the drugs used and the subsequent development of diabetes l Found that Diabetes and HTN are linked, as well as gout and hyperlipidemia, i.e the “metabolic syndrome”. l No link found between the antihypertensive drugs and diabetes regarding causality.

16. Joint National Commission JNC 11980founded on HDFP JNC 21984Intro of ACE, alpha B. JNC 31986Special situations JNC 41988Many agents 1 st line JNC 51993Back to stepped care. JNC 61997ACE for Diabetics JNC 7 2003

17. HYPERTENSION JNC V l "Because diuretics and B-Blockers are the only classes of drugs that have been used in long-term controlled trials and shown to reduce morbidity and mortality, they are recommended as first- choice agents unless they are contraindicated or unacceptable, or unless there are special indications for other agents."

18. HYPERTENSION JNC VII Outline l Epidemiology of HTN l Evaluation of HTN l NON Pharmacologic treatments: Wt loss, diet, exercise, alcohol l Drug treatment l Special Issues in HTN

19. Case Presentation 56 y.o. A.A. male prior weight lifter presents for refractory HTN. Normal labs and UA. Normal CXR and EKG. Meds:Clonidine 0.2 BID ACE inhibitor Diltiazem 300 mg daily

20. Case Presentation Physical Exam: BP 170 / 110 Pulse 85 Edema 2 +

21. Case Presentation Special populations help define your approach. African Americans: CHF Diabetics:

22. Case Presentation Special populations help define your approach. African Americans: Volume Mediated, Low renin low Aldo. CHF:ACE, Diruetics, B-blocker Diabetics:ACE or ARB.

23. Case Presentation 56 y.o. A.A. male with edema, HTN Normal labs and UA. Normal CXR and EKG. Meds:Clonidine 0.2 BID ACE inhibitor Diltiazem 300 mg daily Whats Missing???

24. Stages of Hypertension Normal Prehypertension Stage 1 Stage 2 < 120 / 80 120 -139 / 80-89 140-159 / 90-99 > 160 / >100

25. Treatment of Hypertension Single agent – HCTZ for most pts. B-Blocker for females/ high heart rate. Stage 2 I start with DHP CCB (procardia XL) plus one or both of above. Resistant HTN I look for CLASSES of agents

26. Case Presentation 56 y.o. A.A. male with refractory HTN. Meds:Clonidine 0.2 BID ACE inhibitor - Stopped Diltiazem 300 mg daily I added HCTZ 50 mg daily.

27. Case Presentation 56 y.o. A.A. male with refractory HTN. Meds:Clonidine 0.2 BID Diltiazem 300 mg daily HCTZ 50 mg daily. Still swelling, BP a little better. 156 / 100.

28. Classes of Antihypertensives Diuretics Rate control agentsBBlocker, Verapamil, Diltiazem ACE/ ARB ’ s Vasodilators Dihydropyridines, Hydralazine, Alpha blockers, Minoxidil Central agents: clonidine, aldomet.

29. Case 56 y.o. AA male with refractory HTN. I changed diuretics to Lasix and Zaroxolyn. I get a call 3 days later: Swellings gone, but I can ’ t get out of bed – too dizzy!

30. Case Presentation 56 y.o. A.A. male with refractory HTN. Meds:Lasix 40 mg BID Zaroxolyn 5 mg weekly No swelling, BP 126 / 80. Pt reports joint pain and swelling. What test do you order next?

31. Case Uric acid level is 12 Creatinine 1.4 K 3.8 Glucose 244 (nonfasting)

32. Case Started Allopurinol for gout. Pt started exercising and watching diet. Sugars normalized without treatment.

33. Nephrology level htn I tell the pt that will need to control the main route plus the main detours causing the HTN. Rate control (pulse < 78) Diuretic Vasodilator DHP CCB, Hydralazine, Cardura, Minoxidil. ACE / ARB (accept 30% increase in creat if BP responds)

34. Refer to Nephrologist If unable to control on 3 drug regimen which includes Rate control, diuretic. If you are considering Minoxidil If creatinine climbs more than 30 % or if creatinine is over 2.0.