Amjad AlMahameed, MD, MPH

Systolic Brachial Blood Pressure Discrepancy as a Predictor of Pan Vascular Disease and

Survival

No No symptomssymptoms ++ Symptoms Symptoms

Time Course of Human Atherogenesis

lumen lumenlumen lumen

Time (years)Time (years)

SymptomsSymptoms

Lesion initiationLesion initiation

Cerebrovasc. Cerebrovasc. DiseaseDisease

Ischemic Heart Ischemic Heart DiseaseDisease

Leg PADLeg PAD

What is Peripheral Arterial Occlusive Disease?

• Clinical manifestation of atherosclerosis in the peripheral arteries:

▲ Legs (Iliac, femoropopliteal, crural arteries)

▲ Cerebrovascular: extracranial (such as carotids and vertebral) . intracranial

▲ Arms (subclavian arteries)

▲ Renal arteries

▲ Mesenteric arteries

• > 90% related to atherosclerotic disease

HTN 50 million

Stroke4.4 million

CHF4.6 mill

Heart 16.8 million

AMI7.2 mill

Angina6.3 mill

68 Million Americans with CVD

PAD8.4 million

And many more to come !!

PAD 5-Years Mortality Rates *80% of fatal events are cardiac or stroke

American Cancer Society. Cancer Facts and Figures. 1997

Breast CA Hodgkin's PAD Colon CA Lung CA

100%

80%

60%

40%

20%

0%

28%18%15%

38%

86%

0.0

2.0

4.0

6.0

8.0

10.0

All CausesAll Causes CardiovascularCardiovascularDiseaseDisease

Coronary Heart Coronary Heart DiseaseDisease

PAD and Relative Risk of Death

Cause of DeathCause of Death

3.13.1(1.9–4.9)(1.9–4.9)

5.9 5.9 (3.0–11.4)(3.0–11.4)

6.66.6(2.9–14.9)(2.9–14.9)

Adapted from Criqui MH et al. N Engl J Med. 1992;326:381.Adapted from Criqui MH et al. N Engl J Med. 1992;326:381.

Re

lati

ve

Ris

k (

95

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ela

tiv

e R

isk

(9

5%

CI)

PAD Survival as a Factor of the ABI

Year

100

80

60

40

200 108642

Pat

ien

ts S

urv

ival

(%

) ABI >0.85

ABI 0.40–0.85

ABI <0.40

McKenna M, et al. Atherosclerosis. 1991;87:119-128.

JNC 7: Treatment Algorithm for Hypertension

SBP=systolic blood pressure; DBP=diastolic blood pressure; ACEI=angiotensin- converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=-blocker; CCB=calcium channel blocker

JNC 7. May 2003. NIH publication 03-5233.

Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist.

Not at goal blood pressure

Without compelling indications

Stage 1 hypertension(SBP 140–159 or DBP 90–99 mm Hg)Thiazide-type diuretic for most.May consider ACEI, ARB, BB, CCB, or combination.

Stage 2 hypertension(SBP 160 or DBP 100 mm Hg)Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).

Lifestyle modifications

Not at goal blood pressure (<140/90 mm Hg)(<130/80 mm Hg for those with diabetes or chronic kidney disease)

Initial drug choices

With compelling indications

Drugs for compelling indicationsOther antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB) as needed.

Libby P. Lancet. 1996;348:S4-S7. Carter S, Role of pressure measurement in vascular disease in Bernstein EF, editor, Noninvasive Diagnostic Techniques in Vascular Disease, Mosby, 1985:513-544

Media

Intima

Vessel Lumen

Atherosclerotic Plaque: Effect on Hemodynamics

Encroachment on the lumen by aplaque has to be relatively extensivebefore changes in hemodynamics become manifest:

- Aorta: 90%- Iliac, femoral, carotid, renal: 70-90%

Systolic pressure is sensitive index of the fall in mean pressure while diastolic pressure does not fall untilthe stenosis is severe Measurement of systolic pressure

provides a quantitative, objective, and sensitive index on the occlusive process

Plaque

Vessel Lumen

Hypertension and BBPD: Why Are we Talking About This?

• HTN is a public health problem (50 Million Americans)

• HTN is associated with increased mortality and morbidity1

• HTN is a modifiable risk factor: accurate early diagnosis is vital2

• Earlier guidelines recommended measuring BP in both arms during the initial visit and using the higher pressure for all future measurements6-10

• Very few practitioners follow even the most critical aspects of BP measurements guidelines leading to under and over dx of HTN10

(1) Stamler J et al. Arch Intern Med 1993;153:598(2) Perloff D et al. Circulation 1993;88:2460(3) JNC VII JAMA 2003(4) Williams B et al. BMJ 2004;328:634

(5) WHO, J Hypertension 1999;17:151-183(6-10) JNC-V 1993, AHA: Circulation 1967; 36:980 HTN Reviews BMJ 1979 and 1986, JAMA 1995 (11) Cushman Arch Intern Med 1996;156:1922

• Joint National Committee (JNC-VII)3• British Hypertension Society (BHS-IV)4• World Health Organization (WHO)5

Make no mention of which arm to measure BP in or of BBPD and its significance.

Occlusive Upper Extremity Arterial Disease

• Atheroclerosis

• Takayasu’s disease

• Embolism/thrombus

• Thoracic outlet syndrome

• Complication of angiography

• Buerger’s disease

• Trauma

• Aortic disease (dissection, coarctation, syphilitic aortitis, supravalvular aortic stenosis)

• No specific number for BBPD has been spelled out as clinically significant in textbooks

• BBPD of 10-15 mm Hg should raise suspicion of scubclavian/axilary disease

• Differences of 20-30 mm Hg is indicative of disease

• BBPD may be seen in patients with no known disease

• BBPD may underestimate severity of disease in case of bilateral stenosis

Limitation of BP measurement

Vessel Wall Rigidity:

- More common in L ext. (>10%)

- Related to Monckeberg’s sclerosis

- Seen in DM, chronic cortico- steroid therapy, HD patients, after renal transplantation, neuropathy an surgical sympathectomy

- Manifests as incompressibility of the vessel

Limb /Cuff compatibility (pseudo-elevation or -reduction)

Obstruction in parallel vessels (only higher pressure recorded)

Vasomotor tone changes (exercise and heat effect)

Time, effort, non-reimbursement issues

Effects of Routine Activities on Blood Pressure (adapted from Campbell et al2)

Systolic blood pressure Diastolic blood pressure

Attending a meeting     20     15

Commuting to work     16     13

Dressing     12     10

Walking     12     6

Talking on telephone     10     7

Eating     9     10

Doing desk work     6     5

Reading     2     2

Watching television     0.3     1

24-Hour Ambulatory BP Measurement

Interpreting BP Readings

• The following can cause falsely low pressure reading:

- An arm cuff that is too wide.

- Recent exercise.

- Not smoking for a while after heavy, long-term smoking.

- BP taken in the flaccid paretic arm

• Falsely high pressure can result from the following:

- An arm cuff that is too small.

- Talking during the test.

- Having recently consumed foods or beverages (such as coffee) that raise blood

pressure.

Historical Perspective: What We Knew

• Several studies in the first half of the 20th century found a difference of > 10 mm Hg between arms in 20-45% of patients studied(1-5)

• Most of these studies were small, not standardized, limited to hypertensive patients

• BBPD was much less encountered when measurements were obtained simultaneously after hypertensive patients rested in supine position for 30 minutes (5% of patients had BBPD > 10 mmHg)(6)

• Significant BBPD is present in ambulatory patients presenting to ER without known vascular pathological lesion(7)

(1) Cyriax EF, Q J Med 1921;14:309-313. (2) Kay WE and Gardner KD, West J Med 1930;33:578 (3) JAMA 1939;112:2458. (4) Rueger MJ, Ann Intern Med 1951;35:1023-1027.

(5) Amsterdam B and Amsterdam AL, N Y J Med 1943,43:2294(6) Harrison EG, Roth GM, Hines EAZ, Circulation 1960;22:419(7) Singer AJ and Hollander JE. Arch Intern med 1996;156:2005 2008

Osler 1915: “While the arterial blood pressure in aneurysm is either normal or slightly above, in a majority of cases of

thoracic aneurysm there is a marked difference in the blood pressure in the two arms and when this is greater than 20

mmHg it is a point in favor of aneurysm”

(Osler W. Modern Medicine. Vol 4. Philadelphia, Lea & Fibiger, 1915, P 498)

ABI is 95% sensitive and 99% specific for PAD

Meticulous attention to details is mandatory and the instruments should be calibrated.

Patient should be in supine position.

Beware of ABI limitations

Lower extremity systolic pressureLower extremity systolic pressure

Brachial artery systolic pressureBrachial artery systolic pressure

Korotkoff method

ABI =ABI =

Lower systolic brachial pressure in one arm_____________________________________________________________

Higher systolic brachial pressure in other armBBI =

BP Status Number of participants

Average age (yrs)

BBPD > 10 (mmHg)

Related to sex/ hand dominance

Coefficient of variation

Normotensiv1 100 38 15% No 5%

Hypertensiv2 100 55 18% No 2%

(1) Pesola G et al, Am J Emerg Med 2001;19:43-45)(2) Pesola G et al, Academic Emergency Med 2002;9:342-345)

The “Normal” Difference in Bilateral BP Recordings

Although no objective evaluation of the aortic arch, subclavian or axillary arteries was undertaken, the authors concluded that the 15% and 18% BBPD rate represent “false-positive” results and are related to “normal variability”

accidental participants (by convenience) included hospital workers (physicians, nurses, janitors, etc)

Random BP by 2 observers using standard mercury cuff while seated

Assessment of Interarm BP Differences in the ER

BBPD unrelated to age, sex, race, BP , cardiovascular risk factors, pulse, underlying diagnosis

Mean BBPD was significantly higher in pts w known CAD (14.5 vs. 10.4 mm Hg, P = 0.05)

324 (53%) had a BBPD > 10 mmHg

113 (19%) had a BBPD > 20 mmHg

Prospective observational study on a convenience sample of 610 ambulatory patients seen at a university hospital ER (9/5-23 , 1996)

- Patients were seated

- Automated BP monitor

- “Sequential” BP (R arm then L), 300 pts

- “Almost simultaneous” BP measurement, next 310 pts

Singer AJ and Hollander JE. Arch Intern med 1996;156:2005-2008

462 subjects: 98 with HTN, CAD, PAD (age 68 yrs) and 364 w/o hx of CVD (49 yrs). Supine position for 10 minutes. Mean of 4 simultaneous BP readings (each arm) used for BBPD.

Normal Range of BBPD

Experimental In Clinical Practice

Systolic

W/O CVD - 8 to 10.3 (-8.6 to 10.8) - 8 to 11

All Group - 8.7 to 10.9 (-9.2 to 11.4) - 9 to 11

Diastolic

W/O CVD - 10 to 10 (-10.5 to 10.5) - 10 to 10

All Group - 10.2 to 10.2 (-10.7 to 10.7) - 10 to 10

BBPD is not related to age, gender, mean BP, and history of CVD

Some subjects have clinicallyImportant BBPD

“Normal” range for BBPD (systolic) Is -9 to 11 mmHg

“Normal” range for BBPD (diastolic) Is -10 to 10 mmHg

The normal Range of Interarm Differences in BP (Orme S et al. Age and Ageing 1999;28:537-542)Orme S et al. Age and Ageing 1999;28:537-542)

400 participants (mean age 56), 86 (21%) with history of HTN. Sit quietly for 5 minutes. BP measured simultaneously using 2 automated monitors.

Participants with Clinically Significant Difference in BP (BBPD)

BBPD Quintiles (mmHg), n (%)

0-5 6-10 11-15 16-20 >20

Systolic 231 (57.8) 89 (22.3) 50 (12.5) 16 (4.0) 14 (3.5)

Diastolic 284 (71.0) 71 (17.8) 16 (4.0) 14 (3.5) 15 (3.8)

Systolic BBPD: > 10 mmHg: 80 participants (20%) > 20 mmHg: 14 participants (3.5%) Diastolic BBPD: > 10 mmHg: 45 participants (11%) > 20 mmHg: 15 participants (~4%)

BBPD was not associated with: Age Sex Ethnicity R or L arm circumference Handedness Being hypertensive Previous history of CVD

Lane D et al. J of Hypertension 2002;20:1089-95

BBPD in Nursing Home Residents2

• 237 primary care patients• Systolic BBPD > 20 mmHg: 23%• > 10 mmHg: 40%

• 528 NH residents (able to give IC)• Systolic BBPD > 10 mmHg: 14%• Diastolic BBPD > 10 mmHg: 4%

BBPD in Primary Care Patients1

No association between BBPD (S & D) and:

- HTN - Vascular Dz

- DM

- Dyslipidemia

(1) Cassidy P. J Hum Hypertension, 2001;15:519-522.(2) Mendelson G. Cardiology in Review 2004;12:276-278

52 patients (66 yrs) with occlusive or aneurysmal disease documented or suspected PAD (prior surgery, symptoms of claudication, auscultation of a bruit, absent pulses)

Cardiac Catheterization With nonselective aortic Arch angiography

48 technically acceptable

studies

35.4% had > 30% stenosis

18.7% had > 50% stenosis

1 patient ,total LSC A occlusion

Gutierrez GR et al. Angiology 2001;52:189-194

515 patients referred forCardiac Catheterization

492 had completeData (age 62)

17 (3.5%) subjectshad L SCA stenosis

(> 60%)

Incidence (%)

Overall Population Potential CABG Patients

No significant angiographic CAD 1.4 -

1- or 2-vessel CAD 3.3 -

3-Vessel or left main CAD - 5.3

No PAD 1.5 2.4

HTN 4.3 6.2

Smoking history 4.3 6.5

Diabetes Mellitus 6.8 8.3

Cerebrovascular disease 7.6 9.1

PAD (30% of participants had PAD) 11.5 9errorrrrrrrrrrrr 11.8

English J et al. Cathet Cardiovasc Intervent 2001;54:8-11

The only independent predictor of L SCA

Stenosis: PAD (clinical or documented)

Characteristics of BBPD of > 10 mmHg and > 20 mmHg in predicting L SCA stenosis

• BBPD should not be used as screening method for L SCA stenosis pre CABG

• Proximal L SCA angiography is recommended for patients with > 10 mmHg BBPD or those with clinical evidence of PAD regardless of the BBPD

• If moderate proximal SCA stenosis is present, translesional measurement of the gradient is recommended.

BBPD

> 10 mmHg > 20 mmHg

Sensitivity 65% 35%

Specificity 85% 94%

Positive Predictive Value 13% 19%

Negative Predictive Value 99% 98%

English J et al. Cathet Cardiovasc Intervent 2001;54:8-11

134 hospitalized patients: 58 with PAD, 38 with CAD, and 38 controls (no CAD/PAD). The mean of 3 BP measurements (Dinamap) for each arm used for BBPD calculation (sequentially).

BBPD (absolute systolic BP ∆ mmHg)

> 10 mmHg > 15 mmHg > 20 mmHg > 45 mmHg

Control (n = 38) 5 (13%) 0 (0%) 0 (0%) 0 (0%)

CAD (n = 38) 6 (16%) 3 (8%) 1 (3%) 0 (0%)

PAD (n = 58) 24 (41%)*§ 16 (28%)‡§ 12 (21%)†§ 6 (10%)*§

* P < 0.05 vs. control, † P < 0.01 vs. control, ‡ P < 0.001 vs. control, § P < 0.05 vs. CAD

- No relationship between BBPD and sex, age, smoking, HTN, or diabetes.

- Relatively high incidence and magnitude of BBPD in the PAD group compared to both CAD and control groups

- Does BBPD reflect the atherosclerotic “burden” of a particular patient?

Frank SM et al. Anesthesiology 1991;75:457-463.

Time-to-event survival function plot for clinically important diastolic differences

Clark CE and Powell RJ. Family Practice 2002; 19: 439–441.

• Pairs of BP measurements were taken from 83 of 280 patients (age 69 years) attending general practice (5/94-10/95)

• 64% had HTN, 16% smokers, 11% hx CAD, 5% hx of CVA

• 11 pta (13%) had S BBPD > 20 mmHg

• 14 pts (17%) had D BBPD > 10 mmHg

• 5.6 years F/U

• 17 pts (20%) had CAD events, 2 had CVA, 6 died (1 from cancer and 5 from CVD)

Mean Event-Free Survival (years)

S BBPD > 20 mmHg

D BBPD > 10 mmHg

3.5 (vs. 4.9 years for S BBPD < 20)

3.3 (vs. 5.0 years for DBBPD < 10)

P < 0.0001