Optimal Blood Pressure Thresholds for Minimal Coronary Artery Disease Risk in Type 1 Diabetes

Jingchuan Guo; Maria M. Brooks; Matthew F. Muldoon; Ashely I. Naimi; Trevor J. Orchard; Tina Costacou

doi:10.2337/dc19-0480

Epidemiology/Health Services Research

Optimal Blood Pressure Thresholds for Minimal Coronary Artery Disease Risk in Type 1 Diabetes

Jingchuan Guo¹ ⇑,
Maria M. Brooks¹,
Matthew F. Muldoon²,
Ashely I. Naimi¹,
Trevor J. Orchard¹ and
Tina Costacou¹

¹Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA
²Heart and Vascular Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA

Corresponding author: Jingchuan Guo, jig38{at}pitt.edu

Diabetes Care 2019 Sep; 42(9): 1692-1699. https://doi.org/10.2337/dc19-0480

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Figure 1
Cumulative incidence of CAD by categorized timed-weighted BP over 25 years of follow-up. χ² Test was used for testing the relation between categorized BP and cumulative incidence of CAD. PP, pulse pressure.

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Table 1

Clinical characteristics of the study population at baseline

Variables	Total (N = 605)	Time-weighted BP (mmHg)		Incident CAD
Variables	Total (N = 605)	<120/80 (n = 387)	≥120/80 (n = 218)	No (n = 386)	Yes (n = 219)
Age, years	27.2 (7.7)	25.7 (7.5)	29.8 (7.4)^**	24.8 (7.2)	31.3 (6.8)^**
Age at diabetes onset, years	8.2 (4.1)	8.0 (4.1)	8.5 (4.0)	8.1 (4.2)	8.3 (3.8)
Diabetes duration, year	19.0 (7.4)	17.7 (7.1)	21.3 (7.4)^**	16.7 (6.6)	23.0 (7.1)^**
Female sex, % (n)	49.8 (301)	57.1 (221)	36.7 (80)^**	51.0 (197)	47.5 (104)
SBP, mmHg	112.9 (14.7)	106.3 (8.7)	124.6 (16.1)^**	109.9 (12.3)	118.1 (17.1)^**
DBP, mmHg	72.5 (10.8)	68.1 (7.9)	80.2 (11.1)^**	70.8 (9.8)	75.5 (12.0)^**
PP, mmHg	40.4 (10.3)	38.1 (8.1)	44. 4 (12.4)^**	39.1 (9.6)	42.7 (10.7)^**
MAP, mmHg	85.9 (11.3)	80.9 (7.2)	95.0 (11.6)^**	83.8 (9.8)	89.7 (13.0)^**
Antihypertensive medication use, % (n)	12.9 (78)	5.7 (21)	26.6 (57)^**	7.6 (28)	23.0 (50)^**
Hypertension, % (n)	14.4 (87)	3.6 (14)	33.5 (73)^**	7.8 (30)	26.0 (57)^**
Pulse rate, bpm	78 (10)	76.9 (9.1)	80.5 (10.6)^**	77.4 (9.8)	79.6 (9.7)^*
HbA_1c, % (mmol/mol)	8.8 (73)	8.7 (72)	8.8 (73)	8.8 (73)	8.7 (72)
Ever smoker, % (n)	37.2 (225)	36.2 (140)	39.0 (85)	30.3 (117)	49.3 (108)^**
BMI, kg/m²	23.5 (3.2)	23.2 (3.2)	24.1 (3.2)^**	23.2 (3.2)	24.0 (3.2)^**
High WHR,^† % (n)	4.8 (29)	5.0 (19)	4.6 (10)	5.2 (20)	4.2 (9)
Urinary AER, μg/min	14 (7, 102)	11 (6, 25)	10 (12, 985)^**	11 (7, 42)	39 (9, 470)^**
Raised albuminuria,^‡ % (n)	44.4 (269)	29.7 (115)	70.6 (154)^**	36.5 (141)	58.5 (128)^**
Total cholesterol, mg/dL	189.6 (41.0)	182.7 (36.0)	201.4 (46.2)^**	182.5 (38.9)	202.2 (41.9)^**
LDL cholesterol, mg/dL	114.7 (33.8)	107.9 (28.2)	126.4 (39.1)	108.0 (30.2)	126.7 (36.6)
Non–HDL cholesterol, mg/dL	135.6 (41.0)	128.0 (36.7)	149.6 (46.4)^**	127.6 (38.8)	149.9 (42.9)^**
HDL cholesterol, mg/dL
Men	49.5 (9.8)	50.1 (9.9)	48.7 (9.7)	50.8 (10.0)	47.3 (9.0)^**
Women	58.4 (12.9)	58.4 (12.6)	58.6 (13.7)	58.9 (13.0)	57.5 (12.5)
Triglycerides, mg/dL	82 (60, 121)	77 (57, 106)	92 (66, 141)^**	76 (57, 108)	92 (70, 140)^**

Data presented as percentage (number) are categorical variables; data are otherwise presented as the mean (SD) or median (first quantile, third quantile) and are continuous variables. PP, pulse pressure; WHR, waist-to-hip ratio.
↵*P < 0.05.
↵**P < 0.01 between comparisons of time-weighted BP <120/80 vs. ≥120/80 mmHg, and no CAD vs. CAD.
↵†High WHR was defined as >0.9 in men or >0.85 in women.
↵‡Raised albuminuria was defined as a urinary AER >20 μg/min (30 mg/24 h) in at least two of three validated and timed biennial urine collections.

Table 2

Dose-gradient associations of time-weighted BP and CAD in individuals with childhood-onset type 1 diabetes

	Model 1		Model 2
	HR (95% CI)	P value	HR (95% CI)	P value
SBP, mmHg
<110	0.9 (0.6, 1.3)	0.558	1.1 (0.7, 1.6)	0.801
110 to <120	Reference		Reference
120 to <130	1.7 (1.1, 2.5)	0.013	1.6 (1.1, 2.3)	0.027
130 to <140	2.3 (1.4, 3.7)	<0.001	1.9 (1.2, 3.0)	0.011
≥140	3.3 (2.0, 5.5)	<0.001	2.6 (1.6, 4.5)	<0.001
DBP, mmHg
<60	1.1 (0.6, 1.9)	0.813	0.9 (0.5, 1.7)	0.825
60 to <70	Reference		Reference
70 to <80	1.9 (1.3, 2.8)	<0.001	1.8 (1.2, 2.7)	0.002
80 to <90	5.9 (3.9, 8.9)	<0.001	4.5 (2.9, 6.9)	<0.001
≥90	9.2 (5.2, 16.3)	<0.001	5.6 (3.0, 10.3)	<0.001
MAP, mmHg
<80	0.9 (0.6, 1.3)	0.556	0.9 (0.6, 1.4)	0.718
80 to <90	Reference		Reference
90 to <100	2.9 (2.1, 4.2)	<0.001	2.5 (1.7, 3.5)	<0.001
100 to <110	4.1 (2.6, 6.6)	<0.001	2.9 (1.8, 4.9)	<0.001
≥110	13.9 (7.2, 26.9)	<0.001	8.5 (4.3, 16.8)	<0.001

Model 1 was adjusted for age, sex, diabetes duration, and current use of antihypertensive medications. Model 2 was adjusted for the model 1 variables as well as time-weighted HbA_1c; ever smoking; updated mean BMI, HDL cholesterol, and non–HDL cholesterol; and raised albuminuria.

Table 3

Risk stratification by time-weighted BP and time-weighted HbA_1c for predicting CAD risk in individuals with childhood-onset type 1 diabetes

	Model 1		Model 2
	HR (95% CI)	P value	HR (95% CI)	P value
SBP/DBP
BP ≥120/80 vs. <120/80 mmHg	2.4 (1.8, 3.3)	<0.001	1.9 (1.4, 2.6)	<0.001
BP <120/80 mmHg and HbA_1c <8%	Reference		Reference
BP ≥120/80 mmHg and HbA_1c <8%	2.3 (1.3, 4.3)	0.007	2.0 (1.06, 3.9)	0.033
BP <120/80 mmHg and HbA_1c ≥8%	2.2 (1.4, 3.6)	0.002	1.6 (0.97, 2.8)	0.071
BP ≥120/80 mmHg and HbA_1c ≥8%	5.8 (3.5, 9.7)	<0.001	3.3 (1.9, 6.0)	<0.001
MAP
MAP ≥90 vs. <90 mmHg	3.5 (2.6, 4.7)	<0.001	2.6 (1.6, 3.5)	<0.001
MAP <90 mmHg and HbA_1c <8%	Reference		Reference
MAP ≥90 mmHg and HbA_1c <8%	4.6 (2.5, 8.4)	<0.001	3.4 (1.8, 6.5)	<0.001
MAP <90 mmHg and HbA_1c ≥8%	2.6 (1.6, 4.2)	<0.001	1.9 (1.1, 3.2)	0.016
MAP ≥90 mmHg and HbA_1c ≥8%	8.5 (5.1, 14.1)	<0.001	4.9 (2.7, 8.7)	<0.001

Model 1 was adjusted for age, sex, diabetes duration, and current use of antihypertensive medications. Model 2 was adjusted for the model 1 variables plus ever smoking; updated mean BMI, HDL cholesterol, and non–HDL cholesterol; and raised albuminuria.