United States Preventive Services Task Force: Recommendations for ABPM Michael A. Weber, MD State University of New York Downstate Medical Center

Michael Weber, MD Disclosures Consulting: Boston scientific, Medtronics, Ablative Solutions, ReCor, Novartis Research: Medtronics, Boston Scientific, ReCor, Ablative Solutions, Novartis, Boehringer Ingelheim

Echo-Doppler Values in White Coat Hypertension Control Nonconfirmed * Nonconfirmed True Hypertension LV Septal Thickness (cm) * LV Muscle Mass Index (g/m2) A/E Ratio † * P < .05 † P = .1 Weber MA, et al. Circulation. 1994;90:2291-98.

RAAS and SNS Values in White Coat Hypertension Control Nonconfirmed ** Nonconfirmed True Hypertension Plasma Renin Activity ng/mL/h ** Plasma Aldosterone pg/mL ** * Norepinephrine * P < .05 ** P < .01 Weber MA, et al. Circulation. 1994;90:2291-98.

CHD Rates by SBP, DBP and Age A: Systolic Blood Pressure B: Diastolic Blood Pressure Age at risk: Age at risk: 256 80-89 Years 256 80-89 Years 70-79 Years 70-79 Years 128 128 60-69 Years 60-69 Years 64 64 50-59 Years 50-59 Years 32 32 IHD Mortality (Floating Absolute Risk and 95% CI) 16 IHD Mortality (Floating Absolute Risk and 95% CI) 16 40-49 Years 40-49 Years 8 8 4 4 For every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP, there is a doubling of mortality from both ischemic heart disease and stroke. Data from observational studies involving more than 1million individuals have indicated that death from both ischemic heart disease and stroke increases progressively and linearly from BP levels as low as 115 mm Hg systolic and 75 mm Hg diastolic upward. The increased risks are present in all age groups ranging from 40 to 89 years old. 2 2 1 1 120 140 160 180 70 80 90 100 110 Usual Systolic Blood Pressure (mm Hg) Usual Diastolic Blood Pressure (mm Hg) Adapted from Lewington et al. Lancet. 2002; 360:1903-1913.

USPSTF: Impact of 24-Hour ABP on Risk for CV Outcomes and All-cause Mortality Study, Year Outcome Hazard Ratio (95% CI) Cardiac events or mortality Staessen et al, 1999 Cardiac end points, fatal and nonfatal 1.11 (0.93, 1.31) Dolan et al, 2005 Cardiac mortality (fatal HF, MI, or sudden death) 1.16 (1.07, 1.25) CV events or mortality CV mortality 1.19 (1.13, 1.27) Gasowski et al, 2008 1.42 (1.14, 1.77) Ohkubo et al, 2005 1.27 (1.04, 1.55) 1.11 (0.88, 1.40) Clement et al, 2003 MI or stroke, fatal and nonfatal 1.30 (1.10, 1.55) Hemida et al, 2011 Major CV events (CV death, MI, or stroke) 1.33 (1.17, 1.52) Stroke Stroke, fatal 1.28 (1.15, 1.43) Mesquita-Gastos et al, 2010 Stroke, fatal or nonfatal 1.37 (1.20, 1.56) 1.40 (1.21, 1.62) 1.36 (1.04, 1.79) All-cause mortality 1.02 (0.86, 1.20) 1.13 (1.08, 1.19) 1.09 (0.92, 1.29) ABPM, ambulatory blood pressure; CV, cardiovascular; H.R., hazard ratio; CI, confidence interval; HF, heart failure; MI, myocardial infarction Adapted from: Siu AL, et al. Ann Intern Med. 2016;163:778-786.

What is the result of using ABPM to exclude patients with white coat hypertension? Based on numerous studies cited by the USPSTF about one-third of patients with office hypertension would not be confirmed by ABPM and presumably would not be treated Then what? Should patients have ABPM every year if their office BPs remain high?

What is hypertension? Hypertension can be defined as that level of blood pressure at which, based on robust clinical trial evidence, blood pressure-lowering therapy can be expected to protect patients from major cardiovascular and stroke outcomes NO SUCH DATA EXISTS FOR ABPM: Has the USPSTF confused epidemiology with clinical practice?

Reasons for Concern All major clinical outcomes trial in hypertension have used office based BPs to guide patient recruitment and therapy We can assume that about one-third of patients in those trials had white coat hypertension but presumably still contributed to the observed CV benefits The SPRINT trial and recent meta-analyses showed powerful CV outcome benefits at BP levels that would have been in the same ABPM range as white coat hypertension Over half the patients in HYVET had white coat hypertension and according to the investigators shared fully in the trial’s reduced mortality rates

No. of events per 100 patients HYVET: 21% Reduced Mortality With Active Treatment in Patients Aged 80 or more Active (SBP: 143 mm Hg) versus placebo (SBP: 158 mm Hg) in patients aged 80 or older Placebo group Active treatment group No. of events per 100 patients 30 20 10 4 3 1 2 Follow-up (yr) 202 231 1912 1933 379 420 1492 1565 814 877 No. at risk Placebo group Active-treatment group Beckett NS et al. N Engl J Med. 2008;358:1887–1998.

Time to Stroke Event According to Patient ABP Sub-Type 8 Ambulatory hypertension W h i t e - c o a t h y p e r t e n s i o n 7 6 Normotensive group 5 Cumulative hazard of stroke, % 4 3 2 p = . 1 3 1 T i m e t o s t r o k e , y e a r Verdecchia P et al. Hypertension 2005;45:203-8 1 2 3 4 5 6 7 8 9 1 1 1 1 2 1 3 1 4 1 5 1 6

Conclusion ABPM has a strong relationship to cardiovascular events, perhaps even stronger than office BPs BUT, the recommendation by the USPSTF that the office diagnosis of hypertension should be confirmed by ABPM must be regarded with great caution………until we have clear evidence that labeling patients as “white coat” so as to justify withholding their treatment does not expose them to unacceptable risks of CV events