Blood pressure control measures and cardiovascular outcomes: a prospective hypertensive cohort

Figures & data

Table 1. Baseline and follow-up clinical and BP data according to TTR and systolic BP coefficient of variation groups.

Variable	Total population (n = 1408)	TTR groups				p-value*	Systolic BP CV quartiles				p-value^†
		≤25% (n = 426)	25–39% (n = 309)	40–67% (n = 390)	>67% (n = 283)		≤25% (n = 356)	25–50% (n = 198)	50–75% (n = 390)	>75% (n = 464)
Baseline
Age, years	60 ± 11	63 ± 11	60 ± 10	60 ± 10	58 ± 12	<0.01	59 ± 11	59 ± 10	60 ± 10	62 ± 10	0.01
Male sex, n (%)	672 (48)	209 (49)	140 (45)	177 (45)	146 (52)	0.31	189 (54)	167 (47)	170 (48)	146 (41)	0.02
BMI, Kg/m^2	29 ± 4	29 ± 5	28 ± 5	29 ± 4	28 ± 4	0.56	28 ± 4	29 ± 5	28 ± 4	29 ± 5	0.06
Smoking, n (%)	314 (22)	86 (20)	74 (24)	96 (25)	58 (20)	0.34	76 (22)	81 (23)	83 (23)	74 (20)	0.84
Diabetes, n (%)	257 (18)	102 (24)	58 (19)	59 (15)	38 (13)	0.001	57 (16)	64 (18)	60 (20)	76 (21)	0.29
Dyslipidemia, n (%)	769 (55)	223 (52)	171 (55)	219 (56)	156 (55)	0.71	177 (50)	181 (51)	178 (50)	183 (52)	0.94
Hypertension duration, years	8.6 ± 7.7	10.3 ± 8.7	8.1 ± 6.9	7.8 ± 7.6	7.6 ± 6.6	<0.001	8.7 ± 7.4	8.5 ± 7.3	8.4 ± 7.9	8.6 ± 8.1	0.96
On anti-hypertensive treatment, n (%)	969 (69)	317 (74)	205 (66)	259 (66)	188 (66)	0.03	250 (71)	246 (70)	241 (68)	232 (66)	0.63
Anti-hypertensive agents, n	2.3 ± 1.0	2.6 ± 1.0	2.3 ± 1.0	2.1 ± 0.9	2.1 ± 0.9	<0.001	2.2 ± 1.0	2.2 ± 0.9	2.3 ± 1.0	2.5 ± 1.0	<0.001
RAS blockers, n (%)	1201 (85)	375 (88)	267 (86)	322 (83)	237 (84)	0.15	289 (82)	307 (87)	304 (86)	301 (86)	0.18
CCBs, n (%)	792 (56)	263 (62)	178 (58)	205 (53)	146 (52)	0.02	198 (56)	188 (53)	197 (56)	209 (59)	0.37
Diuretics, n (%)	679 (48)	248 (58)	146 (47)	173 (44)	112 (39)	<0.001	154 (43)	156 (44)	179 (50)	190 (54)	0.014
Beta-blockers, n (%)	490 (35)	172 (40)	108 (35)	115 (29)	95 (34)	0.01	115 (33)	115 (33)	121 (34)	139 (39)	0.16
Anti-aldosterone, n (%)	24 (1.7)	13 (3)	4 (1.3)	6 (1.5)	1 (0.3)	0.045	4 (1)	1 (0.3)	7 (1.9)	12 (3.4)	0.01
Other antihypertensive agents, n (%)	55 (3.9)	18 (4)	17 (5.5)	14 (3.6)	6 (2.1)	0.19	12 (3.4)	14 (3.9)	11 (3.1)	18 (5)	0.52
eGFR, mL/min/m^2	77 ± 18	74 ± 18	79 ± 19	79 ± 18	78 ± 18	0.026	91 ± 31	91 ± 31	86 ± 28	85 ± 28	0.01
Office SBP, mmHg	142 ± 18	152 ± 19	145 ± 17	139 ± 16	131 ± 11	<0.01	137 ± 13	138 ± 15	143 ± 16	150 ± 22	<0.001
Office DBP, mmHg	87 ± 10	90 ± 12	89 ± 12	86 ± 11	84 ± 10	<0.01	86 ± 10	86 ± 11	87 ± 11	88 ± 13	0.006
Office HR, bpm	73 ± 11	74 ± 11	73 ± 10	74 ± 10	72 ± 9	0.46	73 ± 10	72 ± 10	74 ± 10	72 ± 11	0.23
Follow-Up
Visits, n	4.9 ± 2.6	4.7 ± 2.4	4.9 ± 2.6	4.9 ± 2.7	5.1 ± 2.6	0.19	4.3 ± 0.9	4.4 ± 0.8	4.5 ± 0.8	4.2 ± 0.9	0.001
In-treatment systolic BP	137 ± 12	146.5 ± 14	137.6 ± 10	132.5 ± 7.7	129.2 ± 4.6	<0.001	136 ± 12	136 ± 12	138 ± 11	139 ± 13	0.002
TTR, %	45 ± 29	10 ± 10	38 ± 3	60 ± 5	86 ± 10	<0.001	54 ± 38	50 ± 29	42 ± 22	35 ± 21	<0.001
BP coefficient of variation, %	9.1 ± 4.9	9.7 ± 5.6	10 ± 4.2	9.4 ± 4.8	6.1 ± 2.7	<0.001	4.2 ± 1.2	7.0 ± 1.0	9.7 ± 1.7	15.2 ± 5.2	<0.001
Ongoing drug number	2.7 ± 1.1	3.0 ± 1.2	2.7 ± 1.1	2.5 ± 1.1	2.4 ± 1.1	<0.001	2.5 ± 1.1	2.7 ± 1.1	2.6 ± 1.0	2.8 ± 1.2	0.002
RAS blockers, n (%)	1223 (87)	364 (85)	274 (88)	336 (86)	249 (88)	0.54	306 (87)	314 (89)	302 (86)	301 (86)	0.56
CCBs, n (%)	739 (53)	261 (61)	166 (53)	187 (48)	125 (44)	<0.001	172 (49)	185 (53)	190 (54)	192 (55)	0.39
Diuretics, n (%)	842 (60)	288 (68)	192 (62)	221 (57)	141 (50)	<0.001	187 (53)	207 (59)	217 (62)	231 (66)	0.03
Beta-blockers, n (%)	599 (43)	204 (48)	127 (41)	153 (39)	115 (41)	0.06	143 (41)	142 (40)	146 (42)	169 (48)	0.89
Anti-aldosterone, n (%)	89 (6.3)	39 (9)	21 (7)	20 (5)	9 (3)	0.009	18 (5.1)	19 (5.4)	24 (6.8)	28 (7.9)	0.36
Other antihypertensive agents, n (%)	73 (5.2)	45 (11)	14 (5)	11 (3)	3 (1)	0.01	13 (3.7)	18 (5.1)	8 (2.2)	34 (9.6)	0.001
Statins, n (%)	676 (48)	189 (44)	152 (49)	196 (50)	139 (49)	0.34	153 (43)	171 (49)	184 (52)	166 (47)	0.13

BMI: body mass index; BP: blood pressure; CCBs: calcium channel blockers; CV: coefficient of variation; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; HR: heart rate; RAS: renin-angiotensin system; SBP: systolic blood pressure; TTR: time in therapeutic range.

* p-value for the comparison between TTR groups; ^†p-value for the comparison between systolic BP CV groups.

Table 2. Cox regression models for major cardiovascular events setting as predictor variables time to therapeutic range or blood pressure coefficient of variation before and after adjustment for confounders.

Models	Predictor	Univariate model		Multivariate model*
		HR (95% CI)	p-value	HR (95% CI)	p-value
A1	TTR, %	0.98 (0.96–0.99)	<0.001	0.98 (0.96–0.99)	0.001
A2	BP-CV, %	1.06 (1.04–1.08)	<0.001	1.08 (1.05–1.10)	<0.001
A3	TTR, z-score	0.58 (0.48–0.71)	<0.001	0.67 (0.53–0.85)	0.001
A4	BP-CV, z-score	1.35 (1.23–1.48)	<0.001	1.43 (1.27–1.62)	<0.001
B	TTR, z-score	0.62 (0.50–0.75)	<0.001	0.70 (0.55–0.89)	0.004
	BP-CV, z-score	1.18 (0.99–1.40)	0.053	1.24 (1.02–1.52)	0.030
	TTR*BP-CV, z-scores	0.89 (0.78–1.02)	0.103	0.86 (0.74–1.01)	0.053
C	Follow-up systolic BP, mmHg	1.03 (1.01–1.04)	<0.001	1.03 (1.02–1.05)	<0.001
	Follow-up systolic BP, z-score	1.40 (1.17–1.68)	<0.001	1.32 (1.09–1.59)	0.004

A1–A4: Separate models for time in therapeutic range or the blood pressure coefficient of variation before and after standardisation to z-scores; B: common model using together time to therapeutic range: blood pressure coefficient of variation and their interaction term using standardised measures; C: separate models for average achieved systolic blood pressure during follow-up; BP-CV: blood pressure coefficient of variation; CI: confidence interval; HR: hazard ratio; TTR: time to therapeutic range.

* Adjustment was made for the following variables: age, sex, body mass index, smoking status, baseline diabetes mellitus, baseline dyslipidemia, duration of hypertension, baseline systolic blood pressure, baseline diastolic blood pressure, baseline heart rate, plasma glucose, estimated glomerular filtration rate, low-density lipoprotein cholesterol, number of follow-up visits, and antihypertensive treatment at baseline.

Figure 1. Prediction of the composite outcomes in Cox regression models of BP control measures stratified quartiles after adjustment for confounders. (A), quartiles of TTR; (B), quartiles of BP-CV; (C), combined quartiles of both measures.