Pseudohypertension

Osler’s Sign

and

Aortic Arch Calcification

Case ReportOB – 89 y/o man admitted with SOB, cough, knee pain

Past Medical History- Hypertension- Mild CCF- Prostate Ca- Chronic renal impairment (Cr. 250)

MedicationsACE I AmlodipineAspirin Fruesemide 40mg

Pseudohypertension• When BP measured by cuff is falsely elevated

compared to reference standard because of hardened calcific arterial walls

• Pathophysiology - arterial calcification as opposed to atherosclerosis/collagen deposition*

• Associations– Age - Hypertension– Atherosclerosis - Scleroderma

• Prevalence - 1.7% and 2.5% but poorly studied*

* Zuschke et al, Pseudohypertension, Southern Medical Journal 1995, 88:1185-90

Atherosclerotic calcification:– Intimal layer – cellular necrosis,

inflammation and lipid deposition– As lesion progresses, osteogenesis– Typical vascular risk factors, especially

DM and smoking

Monckeberg’s Sclerosis (medial artery calcification)

– Age, diabetes and renal disease– Related to PTH, calcium and phosphate

product, vitamin D and uraemia– Bone-associated cells/proteins important

Osler’s Maneuver

“It may be difficult to estimate how much of the hardness and firmness is due to the tension of blood within the vessel and how much to the thickening of the wall.

For example, when the radial artery can be felt beyond the point of compression, it’s walls are sclerosed”

Sir William Osler, 1892

Osler’s Maneuver• Term coined by Messerli et al (N Engl J Med) in 1985:

– Oslers, sphygmo, ECHO– Strong association between Osler’s and PsHTN

• Usefullness refuted by Prochazka et al (Clin Res) in 1987, due to poor inter-observer reliability

• Subsequently, interobserver agreement 82% with no training effect#

• Prevalence– 1.7%* to 12.3%** (with 0% under 50y/o and 15.6% in over 65y/o)***– Prevalence increases with age, history of hypertension or stroke**

# Hla et al, Observer vasriability of oslers maneuver in detection of pseudohypertension, J Clin Epi 1991, 44:513-18* Kuwajima et al, Pseudohypertension in the elderly, J. Hyperten, 1990, 8:429-32** Wright and Looney, Prevalence of positive osler’s manouvre in 3397 persons screened for the SHEP, Journal of Human Hypertension, 1997, 11:285-289***Prochazka et al, Oslers maneuver in outpatient veterans, J Clin Hypertension, 1987, 3:554-8

Osler’s Maneuver – previous studies

Systematic review using MEsH terms pseudohypertension, Osler’s sign and Osler’s maneuver revealed 8 studies:

– Two examining prevalence of Osler’s sign– One examining observer variability in Osler maneuver– Four comparing radial artery to sphyg in osler-positive– One comparing radial doppler to sphyg in osler-positive

Aortic Arch Calcification

Aortic Arch Calcification• Thoracic aortic calcification has been associated with

increased cardiovascular mortality (hazard ratio between 3 - 6 for IHD and 2.3 for CerebroVD mortality)*

• Strong association with increasing age, hypertension, pulse pressure and smoking

• less association with other known cardiovasc risk factors and CRP** (these studies DID NOT include renal function)

• Clear evidence of association with renal failure- Vitamin D, PTH, calcium and phosphate, ureamia

• Genetic component**** Jacobs et al, Comparing coronary artery calcium and thoracic aortic calcium for prediction of all-cause mortality and cardiovascular events in low-dose

non-gated computed tomography in a high-risk setting of heavy smokers, Atherosclerosis, 2010, 209:455-62* Calcification of the thoracic aorta as detected by spiral computed tomography among stable angina pectoris patients, Circulation, 2008, 118:1328-34** Takasu et al, Relationship of thoracic aortic wall calcification to cardiovascular risk factors: the multi-ethnic study of atherosclerosis (MESA), American

Heart Journal, 2008, 155(4)*** Parikh et al, Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the

framingham offspring and third generation cohorts, Circulation, 2007, 116:1473-81

Oslers maneuver, Pseudohypertension

and Aortic Arch Calcification

Simon Quilty

Nick Collins

Nick Jackson

Paul Puller

Angela Puller

John Attia

• Sequential patients undergoing non-emergency cardiac catheterization in RNC Cath Lab

• Verbal consent – 100% acceptance

• Study participants underwent:– Pre-procedure questionnaire– If recent CXR in past 5 years, Aortic Arch Calcification score calculated– Pre-procedural manual and automatic sphygmo BP– Study blood pressure measurements

Peripheral transduced BPAutomatic sphygmo BP (on non-procedure arm)Central transduced BP

Study Design

Questionnaire• Age, sex• diabetes• hypertension• hyperlipidaemia• Past or current smoking• Number of pack years smoked• Past history ischaemic heart disease• Past history stroke• Past history peripheral vascular disease

Aortic arch calcification calculation

Tetsuya et al, Simple evaluation of aortic arch calcification by chest radiography in haemodialysis patients, Hemodialysis international, 2009, 13:301-306

ResultsParticipant Characteristics

Age 65.8 SD 12.5 Sex (female) 49 35% 139 Blood pressure (cuff) - systolic 136 SD 25 139 - diastolic 65 SD 11 139 BP (transduced peripheral) - systolic 131 SD 22 139 - diastolic 74 SD 12 139 BP (transduced central) - systolic 143 SD 67 139 - diastolic 88 SD 11 139 Oslers positive 14 13.00% 109 Aortic Arch Calcification 3.71 SD 3.69 98 eGFR 65.5 SD 20.6 119 Diabetes 40 32% 125 Hypertension 71 56% 126 Smoker 75 64% 118 Pack years 18.3 SD 19.2 Hyperlipidaemia 54 45% 121 History IHD 52 43% 122 History stroke 14 11% 122

History PVD 4 3% 121

One 52 37%Two 19 14%Three 7 5%Four 1 1%TOTAL 79 57%

Patients with one or more degrees of pseudohypertension (sys, dias, periph, central)

Systolic Diastolic Systolic Diastolic

11% 44% 17% 12%

15mmHg 16.5mmHg 18.4mmHg 14.4mmHg10-40mmHg 10-37mmHg 10-39mmHg 10-26mmHg

Participants defined as pseudohypertension (percent, average cuff over-estimate and range)

Peripheral transduced Central transduced

Age 65.7 SD 12 65.3 SD 13

Sex (female) 5 36% 35 37%

eGFR 58 SD 17 60 SD 20

AoAC 4.4 A = 2.5 2.47 A = 3

Diabetes 3 23% 30 36%Hypertension 8 62% 46 55%Smoker 9 69% 50 63%Pack years 20 A = 18 17 A = 15Hyperlipidaemia 7 54% 33 40%IHD 5 9% 32 39%Stroke 1 8% 6 7%PVD 0 0% 3 4%

Oslers positive Oslers negative

Difference in characteristics based upon Oslers sign

Statistical Analysis

• Inter-rater reliability of Osler’s Sign– Kappa = 0.54– Inter-observer agreement = 89%

Pearson’s correlation - Sphygmo vs Peripheral Transduced BP No correlation between systolicCorrelation between diastolic, P < 0.0001, R = 0.55

0 50 100 150 200-50

-25

0

25

50

Difference (Automatic vs periph TD)

Automaitc press

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-5

20

45

L

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Systolic Diastolic

Automatic Sphyg BP Automatic Sphyg BPDiff

eren

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ansd

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Sphygmo vs Central TransducedBP

Systolic Diastolic

Diff

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ce a

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vs tr

ansd

uced

0 50 100 150 200-50

-25

0

25

50

Difference (Automatic vs central TD)

Automaitc press

0 30 60 90 120-40

-24

-8

8

24

40

56

P

I

No correlation between systolicCorrelation between diastolic, P < 0.0001, R = 0.49

Automatic Sphygmo BP Automatic Sphygmo BP

Osler’s Sign and Pseudohypertension

• Fisher’s exact test

Pseudohypertension as defined as >10mmHg over-estimate of reference (transduced) BP

No statistically significant association between Osler’s Sign and defined pseudohypertension centrally or peripherally, systolic or diastolic

Osler’s Maneuver and Pseudohypertension

• Unpaired t-test – Osler’s Sign and magnitude of difference between automatic and

transduced BP:

– Systolic Pseudohypertension no statistically significant difference

– Diastolic pseudohypertension statistically significant when measured centrally or peripherally

• Central – 4mmHg between osler’s pos/neg (P<0.03)• Peripheral – 16mmHg between osler’s pos/neg (P<0.0001)

• Patients with a positive osler’s maneuver had a diastolic cuff pressure that was on average 16mmHg above transduced

Osler’s Sign and Aortic Arch Calcification

• There was a statistically significant correlation between a positive and negative osler’s sign and extent of aortic arch calcification:

– Osler’s positive – mean AoAC score = 6.7– Osler’s negative – mean AoAC score = 3.28– P = 0.004

Stepwise Multiple Linear Regression – Magnitude of difference in BP

• Oslers sign +/-• Age • Sex • Aortic arch calcification score (0-16) • eGFR • Previous or current smoker• Number of pack yrs of smoking• History of Diabetes• History of HTN • History of dyslipidaemia• Previous history of IHD • Previous history of Stroke• Previous history of PVD

Magnitude of difference in BP - Automatic vs Peripheral transduced

• Systolic– Stroke (-9.77mmHg if +ve Hx, P = 0.01)

• Diastolic– Osler’s Sign positive (+5.28mmHg if Oslers +ve, P = 0.07)– History of IHD (-3.70mmHg if +ve Hx, P = 0.07)

Stepwise Multiple Linear Regression Aortic Arch Calcification

• Same variables plus pressure difference between sphygmo and transducer (systolic, diastolic, central and peripheral)

• Age (+0.08 per yr of age, P = 0.03)• Renal function (-0.06 per eGFR, P = 0.008)• Osler’s sign (+2.32 if Oslers +ve, P = 0.07)

Conclusions

• Pseudohypertension leads to over-treatment of blood pressure

• There is no “gold standard” blood pressure

• In high-risk patients with resistant diastolic hypertension, an Osler’s Maneuver may be useful

• Aortic arch calcification does not assist in risk stratifying in regards to pseudohypertension

Conclusions

Measurement of BP is imprecise however there are strategies that improve accuracy of diagnosis*

*Powers et al, Measuring blood pressure for decision making and quality reporting: where and how many measures? Annals of Internal Mericine, 2011, 154:781-88

Within patient SBP variance and number of measurements

*Powers et al, Measuring blood pressure for decision making and quality reporting: where and how many measures? Annals of Internal Medicine, 2011, 154:781-88

Concurrence between automatic and manual sphygmomanometer

0 50 100 150 200 250-50

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Pre BP automatic

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Automatic BP Automatic BP

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Systolic Diastolic

Linear regression, Two-sided P <0.0001, R = -0.32 (sys) R = 0.06 (dias)

Central transduced vs Peripheral transduced BP

Close to statistically significant correlation for systolic (P = 0.051, R=0.24)Statistically significant correlation for diastolic (P < 0.0001, R=0.48 )

Systolic Diastolic

Diff

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-25

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Difference (CENT vs PERIP TD

Art press CENTRAL

Central BP

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Central BP