Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs

Hypertension is a global public health problem. According to the eighth Joint National Committee, hypertension is defined as a systolic blood pressure (BP) equal to or above 140 mmHg and/or diastolic BP equal to or above 90 mmHg1. The European Society of Cardiology (ESC)/European Society of Hypertension (ESH) 2018 guidelines have defined hypertension as a systolic BP (SBP) ≥140 mmHg and/or a diastolic BP ≥90 mmHg2. There are significant health and economic gains attached to early detection, adequate treatment and good control of hypertension. According to a study done in 2017, 34.1 million (95% uncertainty interval 33.3-35.0) deaths and 1.21 billion (1.14-1.28) disability-adjusted life years (DALY) were attributable to the global burden of disease risk factors. When ranked by risk-attributable DALYs, high SBP was the leading risk factor, accounting for 10·4 million (9.39-11.5) deaths and 218 million (198-237) DALYs3.

In specific population, central BP (CBP) which reflects ascending aortic BP may be more predictive of outcomes as compared to brachial BP4–6. CBP is supposed to indicate the pressure exerted on the heart and brain. The ESC/ESH 2003 guidelines for the management of arterial hypertension acknowledged that CBP might be different from peripheral BP. Several studies indicate that central aortic BP could better reflect the load on the heart and central vasculature and organs7,8.

CBP may be estimated noninvasively by the combination of peripheral BP measurement by conventional sphygmomanometer with pulse wave form analysis monitor9.. Central aortic pulse pressure (CPP) showed better correlation with carotid atherosclerosis and the incidence of cardiovascular events as compared to peripheral PP10–13. The present study was conducted to study the CBP and peripheral BP in hypertensive patients with or without treatment and to study the effect of antihypertensive treatment on CBP and peripheral BP.

Material & Methods

This cross-sectional observational study was conducted on consecutive patients, visiting the outpatient department and patients admitted to the department of Medicine, King George’s Medical University, Lucknow, India, from September 2017 to August 2018. A total of 134 adults aged >30 yr with either SBP ≥140 and/or diastolic BP ≥90 mmHg on at least two occasions by office BP measurement or patients having a history of hypertension with or without treatment were included in this study after taking written informed consent. The study was approved by the Institutional Ethics Committee. Details about antihypertensive treatment taken (drugs) were noted. By history, all hypertensive patients, who were on antihypertensive treatment, were taking their drugs regularly. A total of 134 normotensive healthy individuals (patient’s attendants) were included as controls.

Brachial BP of the patients was measured first by sphygmomanometer and then central aortic BP was measured by Mobil-O-Graph 24 h pulse wave analysis (PWA) Monitor (Euro Medix,Germany). Four parameters were noted which were PBP, central aortic BP, augmentation index (AI) and pulse wave velocity (PWV) to evaluate the stiffness of arterial wall.

Statistical analysis: Data were analyzed with SPSS software version 16 (IBM Corp., Chicago, IL, USA). Measurement data were presented as the mean ± standard deviation of the mean, and t test and Chi-square tests were used to analyze the data.

Results

A total of 268 individuals (134 hypertensive and 134 normotensive healthy individuals) were included in the study. Of the 134 patients with hypertension, 59 (44.03%) were female. In the control group, 64 (47.76%) were female. The mean age of hypertensive patients enrolled in the study (52.37±11.80 yr) was higher (P=0.54) as compared to that of controls (48.10±10.70 yr). The difference in the gender of individuals enrolled as cases and controls was not significant.

Of the 134 hypertensive patients, 44 (32.84%) had no previous history of hypertension (newly diagnosed) and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of the 90 hypertensive patients who were on treatment, 37 (41.11%) patients had uncontrolled peripheral BP and 53 (58.89%) had normal BP. In the patient group, 81 (60.45%) had high BP, while 53 (39.55%) had normal BP (Table I). Mean systolic BP (154.68±13.59 mm Hg) and mean diastolic BP (99.57±11.63) of newly diagnosed patients were higher as compared to mean systolic and diastolic BP of hypertensive patients who were on treatment whether controlled on treatment or not.

Of the 134 hypertensive patients, 89 (66.42%) patients had uncontrolled CBP. All 44 (32.84%) newly diagnosed patients had high CBP. In 90 patients who were on antihypertensive treatment, 45 (50%) had uncontrolled and 45 (50%) had controlled CBP. In controls, 118 (88.06%) patients had controlled and 16 (11.94%) patients had high CBP (Table I).

Mean CSBP (140.9±12.8 mmHg) and mean central diastolic BP (102.9±11.0 mmHg) of newly diagnosed patients was higher as compared to mean CSBP (125.2±18.56 mmHg) and mean central diastolic BP (90.04±12.91) of hypertensive patients who were on treatment. This difference was found to be significant (P<0.001). Mean CSBP (139.7±18.25 mmHg) and mean central diastolic BP (99.76±11.99) of hypertensive patients who were on treatment but had uncontrolled peripheral BP was significantly (P<0.001) higher as compared to mean CSBP (115.09±10.20 mmHg) and mean central diastolic BP (83.26±8.48) of hypertensive patients who were on treatment and had controlled peripheral BP.

Mean PWV, mean AI, mean peripheral pulse pressure (PP), mean central PP and mean MAP of patients are given in Table II. Mean MAP (125.07±10.71) of newly diagnosed patients was significantly (P<0.001) higher than mean MAP (110.53±14.91) of hypertensive patients who were on treatment.

Mean PWV and mean AI of hypertensive patients who had uncontrolled CBP were comparable to hypertensive patients who had controlled CBP (Table III). The difference of mean PP, mean central PP and mean MAP was found to be significant (P<0.001).

Of the 90 hypertensive patients taking treatment, 37 (41.11%) patients were on single-drug therapy, 48 (53.33%) patients were on dual-drug therapy and five (5.56%) patients were on triple-drug therapy. Of the 37 patients who were taking single medicine, 11 (29.73%) patients were on angiotensin receptor blockers (ARB), 22 (59.46%) were on calcium channel blockers (CCBs), one (2.70%) was on alpha-2 agonists and three (8.11%) patients were on beta-blockers (Table IV). Of these 37 patients, 17 had controlled CBP and 21 had controlled peripheral BP. CBP was controlled in majority of patients who were taking CCBs and alpha-2 agonists (Table IV).

Discussion

In our study, patients having SBP ≥140 mmHg or a diastolic BP ≥ 90 mmHg were defined as hypertensives. CPP has been shown to be associated with carotid atherosclerosis and the incidence of cardiovascular events than peripheral PP10–13.

In this study, it was found that of the 90 hypertensive patients who were on treatment, 37 (41.11%) had uncontrolled and 53 (58.89%) had normal peripheral BP.

All newly diagnosed patients had high peripheral BP and high central aortic BP. Mean CSBP and mean central diastolic BP of newly diagnosed patients were higher as compared to hypertensive patients on treatment. Mean CSBP and mean central diastolic BP of hypertensive patients who were on treatment but had uncontrolled peripheral BP was higher as compared to hypertensive patients who were on treatment and had controlled office BP. In control population, all individuals had normal peripheral BP, but 16 (11.94%) had high CBP. Further studies with a larger sample size are needed to answer these questions, such as whether these individuals will develop high peripheral BP in future and whether these individuals, with normal peripheral BP require treatment for control of high CBP.

Mean PWV, mean PP, mean central PP, mean MAP and mean AI of hypertensive patients who had uncontrolled CBP were higher as compared to hypertensive patients who had controlled CBP. These measurements correlate better with atherosclerosis and arterial stiffness.

The Strong Heart Study showed that vascular hypertrophy and extent of atherosclerosis was more strongly related to peripheral pulse pressure (PP) rather than systolic pressure. It also demonstrated that subclinical manifestations of CVD was more strongly related to central pulse pressure (CPP) in comparison to peripheral PP. Future risk of cardiovascular events were more if CPP ≥50 mmHg in hypertensive patients14. A study done in the Argentina population15 showed that PWV was the gold standard method for arterial stiffness quantification. PWV progressively increases 6-8 per cent with each decade of life. A significant increase of PWV over 50 yr was demonstrated in this study15.

The Framingham Heart Study16 showed that total and high-density lipoprotein cholesterol concentrations, smoking, presence of diabetes mellitus, higher aortic PWV was associated with a 48 per cent increase in cardiovascular disease risk. Higher aortic stiffness assessed by PWV was associated with increased risk for a first cardiovascular event.

Majority of patients who were taking CCBs had controlled peripheral and central aortic BP. All three patients who were on beta-blockers had uncontrolled central aortic BP while ARBs were not so effective in controlling central aortic BP. This observation may be because of small number of patients in our study and uneven distribution of patients on various drugs. It was not possible to comment on the effects of various antihypertensive drugs on central aortic BP in this study, as the distribution of patients on various drugs was uneven and the sample size was small. Studies have found that CCBs are effective in controlling central aortic BP and beta-blockers are less effective for control on central aortic BP4,6,17,18.

The Conduit Artery Function Evaluation study, a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial, examined the impact of two different BP-lowering regimens (atenolol/thiazide-based vs. amlodipine/perindopril-based therapy) on derived central aortic pressures and haemodynamics19. This study showed that BP-lowering drugs can have substantially different effects on central aortic pressures and haemodynamic despite a similar impact on brachial BP. CPP may be a determinant of clinical outcomes.

The antihypertensives and blood pressure of central artery study in Japan (ABC-J) demonstrated that vasodilator antihypertensive lowered CBP independently of PBP levels without evident class-specific differences, whereas non-vasodilators antihypertensive drugs may raise CBP4. An open prospective cohort study that was carried out in the Asian hypertensive population showed that central aortic systolic pressure (CASP) was a stronger predictor of cardiovascular events than brachial BP. This study demonstrated a good correlation between CASP and brachial SBP reductions after 12 wk of treatment with valsartan18.

The main limitations of our study were that it was a tertiary hospital-based study, subjected to referral bias. As our study was cross-sectional type, future cardiovascular events could not be predicted and the sample size was small. Also, the duration of hypertension, doses and duration of antihypertensive drugs taken by patients was not taken into account, which might affect the results of this study.

In conclusion, our study showed that patients with a history of hypertension and on treatment had normal peripheral BP but high CBP. Patients who were taking CCB had better control of CBP. Further studies with a large sample size and follow up are needed to establish the role of routine measurement of CBP and effects of antihypertensive treatment on CBP.