Patrick Kay, General and Interventional Cardiologist Auckland or healthpoint.co.nz

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Patrick Kay, General and Interventional Cardiologist Auckland ipatkay@hotmail.com or healthpoint.co.nz Rotorua 2015

Rotorua 2015

Graphical example of true mean and variation, and of regression to the mean using a Normal distribution. Barnett A G et al. Int. J. Epidemiol. 2005;34:215-220 IJE vol.34 no.1 International Epidemiological Association 2004; all rights reserved.

An example of the reduction in the regression to the mean (RTM) effect due to taking multiple baseline measurements and using each subject's mean as the selection variable. Barnett A G et al. Int. J. Epidemiol. 2005;34:215-220 IJE vol.34 no.1 International Epidemiological Association 2004; all rights reserved.

What Does this all mean? A single clinical BP is subject to random error To decrease random error we need to sample more frequently - Clinic samples, Home BP measurements, Ambulatory BPM

The initial evaluation of a patient with hypertension should 1. confirm the diagnosis of hypertension 2. detect causes of secondary hypertension 3. Assess CV risk and end-organ damage

Important Rule -Outs OSA do an Epworth Sleepiness Scale Dietary excesses salt, liqorice etc Alcohol intake NSAIDs, Antidepressants, OCP, Venlafaxine, immune suppressants, steroids Endocrine Cushings, Conns, Hypo/hyperthyroidism, Hyperparathyroidism CKD Phaeochromocytoma Renal Artery Stenosis, Coarctation Some dietary and herbal supplements (e.g., ginseng, ephedra, ma huang, bitter orange)

Guidelines

JNC 8

New aspects Roles of ABPM and HBPM Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. Initiation of antihypertensive treatment. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmhg) in both higher and lower CV risk patients. New therapeutic algorithms for achieving target BP. Revised recommendations on treatment of hypertension in the elderly. Special attention to resistant hypertension and new treatment approaches.

Actual age-adjusted rates for men aged 45 74 years related to systolic blood pressure (based on age-specific rates in Framingham study). Makridakis S, and DiNicolantonio J J Open Heart 2014;1:e000048 2014 by British Cardiovascular Society

Stratification of total CV risk in categories of low, moderate, high and very high risk according to SBP and DBP and prevalence of RFs, asymptomatic OD, diabetes, CKD stage or symptomatic CVD. Subjects with a high normal office but a raised out-of-office BP (masked hypertension) have a CV risk in the hypertension range. Authors/Task Force Members et al. Eur Heart J 2013;eurheartj.eht151 The European Society of Hypertension (ESH) and European Society of Cardiology (ESC) 2013. All rights reserved. For permissions please email: journals.permissions@oup.com.

efinitions of hypertension by office and out-of-office blood pressure levels

Office blood pressure measurement

Electronic device Multiple recordings Quietened room

Out of Office Blood Pressure Assessment Ambulatory BP assessment Home BP assessment Correlation between these 2 modalities is fair to moderate!

Clinical indications for out-of-office blood pressure measurement for diagnostic purposes LVH, Echo aortic dilatation

Ambulatory BP mmhg 200 180 160 Masked Hypertension True hypertension 140 120 True Normotension White Coat Hypertension 135 100 100 120 140 160 180 200 Manual Office BP mmhg From Pickering, Hypertension 1992

CV events per 1000 patient-year 35 30 25 20 15 CV Events 10 5 0 Normal 23/685 White coat 24/656 Uncontrolled 41/462 Masked 236/3125 Bobrie et al. JAMA 2004;291:1342-9

Example of ABPs

Case 1 37 yr old male Well, semi-pro golfer. +ve family history of ischemic heart disease GP BP=150/90mmHg, P=70 Clinic BP 150/100mmHg, both arms. Repeated after 10 mins. ABPM applied

Case 2 56yr Chinese female. Borderline BP readings last 2 years Dyslipidemic GP 146/94, 136/96, 164/102 over last 6 months Clinic 156/98mmHg ABPM apllied

Strategy Start Cilazepril 2.5mg ½ nocte and review in 2 weeks

Case 3 83yr female Multiple admissions to XYH with postural symptoms and palps No pattern to BP but appears to be 130-150 systolic (always D/C in < 18 hours) Seen in O/P with symptoms of fatigue and dizziness and headaches. Poor oral intake. Bloods normal. Holter normal. Echo normal. Meds: Bendrofluazide 25mg, Quinapril 10mg mane, Amlodipine 5mg, Aspirin 100mg ABP performed

Non-dipper

Strategy Improve 24 hour BP control while limiting variability of pressures Plan: Remove short acting anti-hypertensives DRINK, DRINK AND DRINK Stop diuretics Start 2.5 mg Cilazepril at night Review in 3 weeks

Advantages of ABPM Overcomes the variability seen in GP/clinic/hospital environments Many measurements in a home/work environment Allows greater buy-in / understanding from patients Closely correlated to end-organ CV events (ARTEMIS STUDY) Allows understanding of diurnal variation of blood pressure-dipper / non-dipper. Non-dippers strongly correlated with CVD events and end organ damage LVH, IMT and CVD death

Economics of ABPM Speeds up diagnosis and decreases misdiagnosis International use < 5% and in NZ<1% Eliminate from treatment up to 25% of newly presenting people with elevation of BP UK 2.5 million to implement, cost neutral at year 2 and $10 million saving at year 5 Highest savings were seen in older patients Lovibond K, Jowett S, Barton P, et al. Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study. Lancet 2011; DOI:10.1016/S0140-6736(11)61184-7.

Home BP recordings How Do You Do It? Morning and evening for 7 days Quiet room rested for 5 mins Arm and back supported with cuff at the level if the heart Logbook or preferrably electronic database (avoids editing by patient) Exclude first day of monitoring The Home BP is the average of all recordings of the 6/7 days BUT unlike ABPM does not give data : during routine activities during sleep To quantify short term BP variability

Home BP recordings Better than office BP at predicting CV events and more closely correlated to development LVH and CV morbidity and mortality As good as ABPM for end-organ risk and CV events

(A) Hippocrates (B) Nikolai Korotkoff (C) New York Insurance Company Actuaries in the 1920s (D) The Framingham Study Group in 1961

Dietary salt restriction Weight loss DASH diet Exercise Limited alcohol intake Vitamin D Patient education Smoking / NSAIDs

Monotherapy vs. drug combination strategies to achieve target BP. Moving from a less intensive to a more intensive therapeutic strategy should be done whenever BP target is not achieved. Authors/Task Force Members et al. Eur Heart J 2013;eurheartj.eht151 The European Society of Hypertension (ESH) and European Society of Cardiology (ESC) 2013. All rights reserved. For permissions please email: journals.permissions@oup.com.

ALLHAT BP Results by Treatment Group Chlorthalidone Amlodipine Lisinopril 150 90 145 85 mm Hg BP 140 mm Hg BP 80 135 75 130 70 0 1 2 3 4 5 6 Years 0 1 2 3 4 5 6 Years Compared to chlorthalidone: SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg). Compared to chlorthalidone: DBP significantly lower in the amlodipine group (~1 mm Hg), similar in the lisinopril group. 43

Primary Non-fatal MI (incl. silent) + fatal CHD Secondary Non-fatal MI (excl. silent) + fatal CHD Total coronary endpoint Total CV events and procedures All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Unadjusted hazard ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-0.78) 0.85 (0.75-0.97) Post hoc Primary endpoint + coronary revasc procs CV death + MI + stroke 0.50 0.70 1.00 1.45 2.00 Amlodipine perindopril better Atenolol thiazide better The area of the blue square is proportional to the amount of statistical information 0.86 (0.77-0.96) 0.84 (0.76-0.92)

Mean BP before and during spironolactone treatment. Effect in 1411 ASCOT participants who received spironolactone for treatment of high BP with available BP measurements before (pre-), and during (post-), spironolactone

Cilazepril 0.5-5.0 (1))

Start Cilazepril or Lisinopril/ Amlodipine / Chlorthalidone Keep adding within the first 3 4 th choice - consider use of Spironolactone. 5 th choice - beta blockers, and/or selective alpha blockers. Beta blockers are not a preferred initial therapy for hypertension, but consider in women of child-bearing potential, or patients with evidence of increased sympathetic drive. With use of beta blocker consider co-administration with alpha blocker.

Accurate diagnosis 24HR BP or Home recording Right drugs: ACE-I/ Ca2+ blocker/ Chlorthalidone 4 th choice Spironolactone (watch Na+, K+ and renal fn) 5 th choice Beta blocker; the alpha blocker Check Na+, K= and renal function Consider invasive devices if PO regimen does not work/poorly tolerated

Patrick Kay, General and Interventional Cardiologist Auckland ipatkay@hotmail.com or healthpoint.co.nz Rotorua 2015

A/Prof I Patrick Kay, Middlemore, Auckland City, Mercy Hospitals Private Clincs: Apollo, Silverdale, Eastcare, Pukekohe

Gaps in evidence and need for future trials Should antihypertensive drug treatment be given to all patients with grade 1 hypertension when their CV risk is low-to-moderate? Should elderly patients with a SBP between 140 and 160 mmhg be given antihypertensive drug treatments? Should drug treatment be given to subjects with white-coat hypertension? Can this condition be differentiated into patients needing or not needing treatment? Should antihypertensive drug treatment be started in the high normal BP range and, if so, in which patients? What are the optimal office BP values (i.e. the most protective and safe) for patients to achieve by treatment in different demographic and clinical conditions? Do treatment strategies based on control of out-of-office BP provide an advantage (reduced clinical morbidity and mortality, fewer drugs, fewer side-effects) over strategies based on conventional (office) BP control? What are the optimal out-of-office (home and ambulatory) BP values to be reached with treatment and should targets be lower or higher in high risk hypertensives? Does central BP add to CV event prediction in untreated and treated hypertensive patients? Do invasive procedures for treatment of resistant hypertension compare favourably with the best drug treatment and provide long-term BP control and reduction of morbid and fatal events? Do treatment-induced changes in asymptomatic OD predict outcome? Which measures or combinations of measures are most valuable? Are lifestyle measures known to reduce BP capable of reducing morbidity and mortality in hypertensive patients? Does a treatment-induced reduction of 24h BP variability add to CV protection by antihypertensive treatment? Does BP reduction substantially lower CV risk in resistant hypertension?

White Coat and Masked Hypertension Both seen in 13% hypertensive population White Coat associations: age, female, non-smoking Masked hypertension associations: younger age, male, exercise Obesity, diabetes, CKD, family history of hypertension. CV events equate to true sustained hypertension. In diabetic patients Sustained nocturnal hypertension may occur leading to nephropathy