1. Amjad AlMahameed, MD, MPH Systolic Brachial Blood Pressure Discrepancy as a Predictor of Pan Vascular Disease and Survival

2. No symptoms + Symptoms Time Course of Human Atherogenesis lumen Time (years) Symptoms Lesion initiation Cerebrovasc. Disease Ischemic Heart Disease Leg PAD

3. 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

4. HTN 50 million Stroke 4.4 million CHF 4.6 mill Heart 16.8 million AMI 7.2 mill Angina 6.3 mill 68 Million Americans with CVD PAD 8.4 million And many more to come !!

5. PAD 5-Years Mortality Rates * 80% of fatal events are cardiac or stroke American Cancer Society. Cancer Facts and Figures. 1997 Breast CAHodgkin'sPAD Colon CA Lung CA 100% 80% 60% 40% 20% 0% 28% 18% 15% 38% 86%

6. 0.0 2.0 4.0 6.0 8.0 10.0 All Causes CardiovascularDisease Coronary Heart Disease PAD and Relative Risk of Death Cause of Death 3.1(1.9–4.9) 5.9(3.0–11.4) 6.6(2.9–14.9) Adapted from Criqui MH et al. N Engl J Med. 1992;326:381. Relative Risk (95% CI)

7. PAD Survival as a Factor of the ABI Year 100 80 60 40 20 0 10 8 6 4 2 Patients Survival (%) ABI >0.85 ABI 0.40–0.85 ABI <0.40 McKenna M, et al. Atherosclerosis. 1991;87:119-128.

8. 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 indications Other antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB) as needed.

9. 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 a plaque has to be relatively extensive before 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 until the stenosis is severe Measurement of systolic pressure provides a quantitative, objective, and sensitive index on the occlusive process Plaque Vessel Lumen

10. 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 morbidity 1 HTN is a modifiable risk factor: accurate early diagnosis is vital 2 Earlier guidelines recommended measuring BP in both arms during the initial visit and using the higher pressure for all future measurements 6-10 Very few practitioners follow even the most critical aspects of BP measurements guidelines leading to under and over dx of HTN 10 (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.

11. 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

12. 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

13. Effect on blood pressure (mm Hg) Effects of Routine Activities on Blood Pressure (adapted from Campbell et al 2 ) Systolic blood pressureDiastolic 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 Watching television  0.3  1

14. 24-Hour Ambulatory BP Measurement

15. 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.

16. Historical Perspective: What We Knew Several studies in the first half of the 20 th 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)

17. 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 pressure Brachial artery systolic pressure Korotkoff method ABI = Lower systolic brachial pressure in one arm _____________________________________________________________ Higher systolic brachial pressure in other arm BBI =

18. BP StatusNumber of participants Average age (yrs) BBPD > 10 (mmHg) Related to sex/ hand dominance Coefficient of variation Normotensiv 1 1003815%No5% Hypertensiv 2 1005518%No2% (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

19. 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

20. 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 ExperimentalIn 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 clinically Important BBPD “Normal” range for BBPD (systolic) Is -9 to 11 mmHg “Normal” range for BBPD (diastolic) Is -10 to 10 mmHg Orme S et al. Age and Ageing 1999;28:537-542) The normal Range of Interarm Differences in BP (Orme S et al. Age and Ageing 1999;28:537-542)

21. 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 (%) 0-56-1011-1516-20>20 Systolic231 (57.8)89 (22.3)50 (12.5)16 (4.0)14 (3.5) Diastolic284 (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

22. BBPD in Nursing Home Residents 2 237 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 Patients 1 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

23. 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

24. 515 patients referred for Cardiac Catheterization 492 had complete Data (age 62) 17 (3.5%) subjects had L SCA stenosis (> 60%) Incidence (%) Overall Population Potential CABG Patients No significant angiographic CAD1.4- 1- or 2-vessel CAD3.3- 3-Vessel or left main CAD-5.3 No PAD1.52.4 HTN4.36.2 Smoking history4.36.5 Diabetes Mellitus6.88.3 Cerebrovascular disease7.69.1 PAD (30% of participants had PAD)11.5 9errorrrrrrrrrrrr11.8 English J et al. Cathet Cardiovasc Intervent 2001;54:8-11 The only independent predictor of L SCA Stenosis: PAD (clinical or documented)

25. 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 Sensitivity65%35% Specificity85%94% Positive Predictive Value13%19% Negative Predictive Value99%98% English J et al. Cathet Cardiovasc Intervent 2001;54:8-11

26. 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%) 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.

27. 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