Identifying and treating high blood pressure in men under 55 years with grade 1 hypertension: the TREAT CASP study and RCT
Authors: Williams Bryan , McFarlane Ewan , Jedrzejewski Dawid , Lacy Peter S 
Published: December 2019

Background
There is uncertainty regarding whether or not younger (i.e. aged < 55 years), low-risk patients with grade 1 hypertension (i.e. a clinic blood pressure of 140–159/90–99 mmHg) should be treated with blood pressure-lowering medication. This is a heterogeneous group of patients because of variation in systolic/pulse pressure amplification from the central aorta to the brachial artery. It is hypothesised that within grade 1 hypertension, patients can be divided into those with high central aortic systolic pressure and those with low central aortic systolic pressure.

Objectives
The aims of this study were to (1) evaluate whether or not non-invasive central aortic systolic pressure measurement can better identify younger patients with grade 1 hypertension, who are more likely to have an increased left ventricular mass index; and (2) determine whether or not blood pressure lowering regresses early cardiac structural change in patients with high central aortic systolic pressure.

Setting
A university hospital with satellite primary care recruitment sites.

Participants
A total of 726 men (aged 18 to < 55 years) were screened to identify 162 men with grade 1 hypertension and low or high central aortic systolic pressure. Blood pressure status was classified according to seated clinic blood pressure, central aortic systolic pressure and 24-hour ambulatory blood pressure.

Design
(1) Evaluating the strength of the correlation between central aortic systolic pressure, clinic blood pressure and 24-hour ambulatory blood pressure with left ventricular mass index in 162 patients; (2) a 12-month randomised controlled trial in patients with grade 1 hypertension and high central aortic systolic pressure (i.e. a central aortic systolic pressure of ≥ 125 mmHg) (n = 105), using a prospective, open, blinded, end-point design; and (3) a 12-month observational study in 57 patients with grade 1 hypertension and low central aortic systolic pressure (i.e. a central aortic systolic pressure of < 125 mmHg).

Interventions
Randomised controlled trial – patients with high central aortic systolic pressure randomised to blood pressure lowering medication (50–100 mg of losartan ± 5–10 mg of amlodipine once daily) versus usual care (no treatment) for 12 months.

Main outcomes
Randomised controlled trial primary end point – change in left ventricular mass index as measured by cardiac magnetic resonance imaging, comparing treatment with no treatment.

Results
(1) At baseline, left ventricular mass index was higher in men with high central aortic systolic pressure than in those with low central aortic systolic pressure (mean ± standard deviation 67.9 ± 8.8 g/m2 vs. 64.0 ± 8.5 g/m2; difference 4.0 g/m2, 95% confidence interval 1.1 to 6.9 g/m2; p < 0.01). Central aortic systolic pressure was not superior to clinic blood pressure as a determinant of left ventricular mass index. Univariate analysis, regression coefficients and slopes for left ventricular mass index were similar for clinic systolic blood pressure, ambulatory systolic blood pressure and central aortic systolic pressure. (2) In the randomised controlled trial, blood pressure-lowering treatment reduced central aortic systolic pressure (–21.1 mmHg, 95% confidence interval – 24.4 to –17.9 mmHg; p < 0.001) and clinic systolic blood pressure (–20.0  mmHg, 95% confidence interval – 23.3 to –16.6 mmHg; p < 0.001) versus no treatment. Treatment was well tolerated and associated with a greater change (i.e. from baseline to study closeout) in left ventricular mass index versus no treatment [–3.3 g/m2 (95% confidence interval –4.5 to –2.2 g/m2) vs. –0.9 g/m2 (95% confidence interval –1.7 to –0.2 g/m2); p < 0.01], with a medium-to-large effect size (Cohen’s d statistic –0.74). (3) Patients with low central aortic systolic pressure had no significant change in left ventricular mass index after 12 months (mean change –0.5 g/m2, 95% confidence interval –1.2 to 0.2 g/m2; p = 0.18).

Conclusions
Men with grade 1 hypertension and high central aortic systolic pressure tended to have higher clinic blood pressure and more hypertension-mediated cardiac structural change than those with low central aortic systolic pressure. Central aortic systolic pressure was not superior to clinic blood pressure or ambulatory blood pressure at stratifying risk of increased left ventricular mass index. Blood pressure-lowering treatment led to a regression of left ventricular mass index in men with grade 1 hypertension and high central aortic systolic pressure compared with no treatment.

Limitations
The study was limited to a moderate sample of men and there was a low prevalence of very high amplification.

Future work
Evaluating effects of blood pressure lowering on cardiac function.

Trial registration
Current Controlled Trials ISRCTN09502665.

Funding
This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership and will be published in full in Efficacy and Mechanism Evaluation; Vol. 6, No. 13. See the NIHR Journals Library website for further project information.