Pseudohypertension Osler’s Sign and Aortic Arch Calcification

Case Report

OB – 89 y/o man admitted with SOB, cough, knee pain Past Medical History Hypertension Mild CCF Prostate Ca Chronic renal impairment (Cr. 250) Medications ACE I Aspirin Amlodipine 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 – Atherosclerosis - Hypertension - 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

Study Design

• 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 BP Automatic sphygmo BP (on non-procedure arm) Central transduced BP

• • • • • • • • •

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

Results

Participant Characteristics

Age Sex (female) Blood pressure (cuff) - systolic - diastolic BP (transduced peripheral) - systolic - diastolic BP (transduced central) - systolic - diastolic Oslers positive Aortic Arch Calcification eGFR Diabetes Hypertension Smoker Pack years Hyperlipidaemia History IHD History stroke History PVD 65.8 SD 12.5 49 35% 139 136 65 131 74 SD 25 SD 11 SD 22 SD 12 139 139 139 139 143 88 SD 67 SD 11 14 13.00% 3.71 SD 3.69 65.5 SD 20.6 40 71 75 32% 56% 64% 18.3 SD 19.2 54 45% 121 52 14 43% 11% 122 122 139 139 109 98 119 125 126 118 4 3% 121

Participants defined as pseudohypertension

(percent, average cuff over-estimate and range)

Peripheral transduced

Systolic 11% 15mmHg 10-40mmHg Diastolic 44% 16.5mmHg

10-37mmHg

Central transduced

Systolic 17% 18.4mmHg

10-39mmHg Diastolic 12% 14.4mmHg

10-26mmHg

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

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

Difference in characteristics based upon Oslers sign

Oslers positive Oslers negative Age Sex (female) eGFR 65.7

5 58 SD 12 36% SD 17 65.3

35 60 SD 13 37% SD 20 AoAC Diabetes Hypertension Smoker Pack years Hyperlipidaemia IHD Stroke PVD 4.4

3 8 9 20 7 5 1 0 A = 2.5

23% 62% 69% A = 18 54% 9% 8% 0% 2.47

30 46 50 17 33 32 6 3 A = 3 36% 55% 63% A = 15 40% 39% 7% 4%

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 systolic Correlation between diastolic, P < 0.0001, R = 0.55

Systolic

Difference (Automatic vs periph TD) 50 45 L

Diastolic

25 0 -25 -50 0 20 -5 30 50 100 150 Automaitc press

Automatic Sphyg BP

200 -30 0 60 90

Automatic Sphyg BP

120 I

Sphygmo vs Central TransducedBP

No correlation between systolic Correlation between diastolic, P < 0.0001, R = 0.49

Difference (Automatic vs central TD) 50 25 0 -25 -50 0

Systolic

50 100 150 Automaitc press

Automatic Sphygmo BP

200 -24 -40 0 56 P 8 -8 40 24

Diastolic

30 60 90

Automatic Sphygmo BP

120 I

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

Difference 50 25 0 -25 -50 0

Concurrence between automatic and manual sphygmomanometer

Linear regression, Two-sided P <0.0001,

R = -0.32 (sys) R = 0.06 (dias)

Systolic Diastolic

50 100 -30 150 200 Pre BP automatic

Automatic BP

250 -50 0 30 F 10 -10 30 60 90

Automatic BP

D 120

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

Difference (CENT vs PERIP TD 50 25 0 -25 -50 0 50 100 -20 -40 20 0 40 S

Diastolic

150 200 Art press CENTRAL

Central BP

250 -60 0 20 40 60 80

Central BP

100 U