HYPERTENSION

Background for understandingthe Hypertension literature.

Jeffrey J. Kaufhold, MDNephrology

HYPERTENSION

SUMMARY Background for understanding

the literature of Hypertension

Review of Joint National Commission Recommendations (VII) 2003

Clinical Evaluation and Case history.

Nat’l Health & Nutrition Exam Survey NHANES

JNC 7 Dec 2003

Why do we treat Hypertension?

• What target for Systolic?• What target for Diastolic?• Which drugs to use?• What complications to watch out for?

HypertensionLiterature Summary

Malignant Hypertension - 1958 Kincaid-Smith and others DBP > 130

used “old” drugs like Guanabenz, Hydralazine

Showed that attempt to treat was enough to significantly reduce mortality from stroke, heart failure, renal failure.

HypertensionLiterature Summary

VA Cooperative Studies - 1967 DBP 115-129 mm Hg - 1970 DBP 90 -114 mm Hg

Used the new drug Inderal, hydralazine, Chlorthaladone

Demonstrated that reducing DBP below 90 significantly reduced mortality from Stroke, Heart failure and renal failure

HYPERTENSION

Literature Summary US Public Health Service

1977 Prospective placebo controlled trial for DBP 90-115 mm Hg

HDFP 1979 Introduced concept of Stepped Care

Oslo Study 1980 Treatment of Mild Hypertension

Medical Research Clinics (MRC) 1985 Single blind and community based.

HYPERTENSION

Literature Summary HDFP

1979 Introduced concept of Stepped Care

step 1 : B-blocker

Step 2 : Diuretic

Step 3 : Hydralazine

Step 4 : Clonidine or aldomet

Step 5 : Minoxidil

HYPERTENSION

PARALLEL WORK 1948 to 1972 Framingham Study

1982 MRFIT

1984 LRC (Lipid Research Clinics)

HYPERTENSION

PARALLEL WORK 1948 to 1972 Framingham Study

20 year follow-up on 5000 pts

Picked Framingham Mass as the town had low turnover

Observational study that defined the risk factors for heart disease

Did not look at treatment and cannot be used to guide treatment

HYPERTENSION

PARALLEL WORK 1982 MRFIT Multiple Risk Factor

Intervention Trial

Randomized primary prevention trial Lower than expected rate of mortality in controls led to NS reduction.

The Usual care group showed a “study effect” as a result of publication of VA and other study results

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.

HYPERTENSION

PARALLEL WORK 1984 LRC (Lipid Research Clinics)

Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

Due to increased suicide, homicide and Motor Vehicle accidents in the study group.

Interesting to note that in studies of rats on low cholesterol diet, the incidence of violent behavior increases.

HYPERTENSION

PARALLEL WORK 1948 to 1972 Framingham Study

20 year follow-up on 5000 pts

1982 MRFIT Randomized primary prevention trial Lower than expected rate of mortality in controls led to NS reduction.

1984 LRC (Lipid Research Clinics) Treatment of hyperlipidemia reduced risk of heart disease, all-cause mortality not effected.

HYPERTENSION

Recent Works 1985 HDFP follow-up Study

Long term surveillence for drug side effects: 9-25 %

1993 VA Cooperative Study, Materson, NEJM Compares 6 agents. Efficacy in 55 % range. Drug intolerance 6 to 14 %.

No significant difference in control between drug classes

No significant benefit by drug class between races

No significant difference in side effect risk

HYPERTENSION

Recent Works 1992 Gurwitz Ann Int Med

Antihypertensive therapy and the initiation of Treatment for Diabetes.

Looked at link between the drugs used and the subsequent development of diabetes

Found that Diabetes and HTN are linked,as well as gout and hyperlipidemia, i.e the “metabolic syndrome”.

No link found between the antihypertensive drugs and diabetes regarding causality.

Joint National Commission

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

HYPERTENSION

JNC V "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."

HYPERTENSION

JNC VII Outline Epidemiology of HTN

Evaluation of HTN

NON Pharmacologic treatments: Wt loss, diet, exercise, alcohol

Drug treatment

Special Issues in HTN

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

Case Presentation

• Physical Exam:• BP 170 / 110 Pulse 85• Edema 2 +

Case Presentation

• Special populations help define your approach.

• African Americans: • CHF• Diabetics:

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.

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???

Stages of Hypertension

•Normal

•Prehypertension

•Stage 1

•Stage 2

•< 120 / 80

•120 -139 / 80-89

•140-159 / 90-99

•> 160 / >100

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

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.

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.

Classes of Antihypertensives

• Diuretics• Rate control agents BBlocker, Verapamil,

Diltiazem• ACE/ ARB’s• Vasodilators Dihydropyridines, Hydralazine,

Alpha blockers, Minoxidil• Central agents: clonidine, aldomet.

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!

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?

Case

• Uric acid level is 12• Creatinine 1.4• K 3.8• Glucose 244 (nonfasting)

Case

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

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)

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.