Impacts of Pre-Diabetes or Prehypertension on Subsequent Occurrence of Cardiovascular and All-Cause Mortality among Population without Cardiovascular Diseases

Figures & data

Figure 1 Research flowchart.

Table 1 Baseline Characteristics of the Participants

	Overall	No Pre-Diabetes		Pre-Diabetes		P-value
		No PreHTN	PreHTN	No PreHTN	PreHTN
	(n=23,622)	(n=12,272)	(n=5841)	(n=2757)	(n=2752)
Age, y	37.2 ± 15.5	32.2 ± 12.6	39.7 ± 16.2	42.2 ± 15.5	49.4 ± 16.2	<0.001
Gender, %						<0.001
Male	11,233 (47.6%)	4562 (37.2%)	3618 (61.9%)	1327 (48.1%)	1726 (62.7%)
Female	12,389 (52.4%)	7710 (62.8%)	2223 (38.1%)	1430 (51.9%)	1026 (37.3%)
Ethnicity, %						<0.001
Non-white	13,235 (56.0%)	6866 (55.9%)	3005 (51.4%)	1745 (63.3%)	1619 (58.8%)
White	10,387 (44.0%)	5406 (44.1%)	2836 (48.6%)	1012 (36.7%)	1133 (41.2%)
Smoking, %	8998 (38.1%)	4104 (33.4%)	2436 (41.7%)	1167 (42.3%)	1291 (46.9%)	<0.001
Less than high school education, %	4950 (21.0%)	2205 (18.0%)	1210 (20.7%)	724 (26.3%)	811 (29.5%)	<0.001
BMI, kg/m2	27.3 ± 6.04	26.1 ± 5.49	28.0 ± 6.16	28.7 ± 6.26	29.8 ± 6.58	<0.001
SBP, mmHg	115 ± 11.0	108 ± 7.34	125 ± 6.56	110 ± 6.90	127 ± 6.46	<0.001
DBP, mmHg	67.9 ± 10.8	64.5 ± 9.36	73.4 ± 11.3	66.0 ± 8.91	73.4 ± 10.8	<0.001
TC, mg/dl	193 ± 41.4	187 ± 40.5	197 ± 41.6	198 ± 41.0	206 ± 40.0	<0.001
HDL-C, mg/dl	53.4 ± 15.5	55.1 ± 15.3	52.9 ± 16.0	51.0 ± 15.0	49.7 ± 14.7	<0.001
Non-HDL-C, mg/dl	140 ± 41.6	132 ± 39.7	144 ± 42.2	147 ± 41.6	157 ± 40.9	<0.001
Energy intake, kcal	2290 ± 1080	2260 ± 1060	2380 ± 1160	2200 ± 1050	2250 ± 999	<0.001
eGFR, mL/min/1.73m2	98.6 ± 29.7	104 ± 32.2	95.1 ± 27.0	93.8 ± 25.1	88.2 ± 21.9	<0.001
Baseline cancer, %	980 (4.1%)	355 (2.9%)	274 (4.7%)	163 (5.9%)	188 (6.8%)	<0.001
Statin use, %	608 (2.6%)	139 (1.1%)	167 (2.9%)	134 (4.9%)	168 (6.1%)	<0.001
Antiplatelet drugs, %	16 (0.1%)	2 (0.0%)	6 (0.1%)	3 (0.1%)	5 (0.2%)	0.008
Low HDLC, %	6840 (29.0%)	3319 (27.0%)	1560 (26.7%)	995 (36.1%)	966 (35.1%)	<0.001
All-cause mortality, %	1039 (4.4%)	345 (2.8%)	336 (5.8%)	118 (4.3%)	240 (8.7%)	<0.001
Cardiovascular mortality, %	98 (0.4%)	19 (0.2%)	39 (0.7%)	12 (0.4%)	28 (1.0%)	<0.001

Note: Data are mean ± SD or percentage.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; HTN, hypertension.

Figure 2 Kaplan-Meier analysis for all-cause and cardiovascular mortality in different groups. (A), all-cause mortality; (B), cardiovascular mortality.

Abbreviations: DM, diabetes mellitus; HTN, hypertension.

Table 2 Multivariate Cox Regression Analysis for Mortality in Different Models

All-Cause Mortality
HRs (95% CI)
	Case/total	Model1	Model2	Model3
		N=23,622	N=23,622	N=19,674
preDM (-) & preHTN (-)	345/12,272	1.00(ref)	1.00(ref)	1.00(ref)
preDM (-) & preHTN (+)	336/5841	1.98(1.71,2.3)	0.96(0.82,1.13)	1.04(0.88,1.24)
preDM(+) & preHTN (-)	118/2757	2.09(1.69,2.57)	0.92(0.74,1.14)	0.96(0.76,1.21)
preDM(+) & preHTN(+)	240/2752	3.97(3.36,4.68)	1.06(0.89,1.27)	1.19(0.98,1.46)
Cardiovascular mortality
HRs (95% CI)
	Case/total	Model1	Model2	Model3
		N=23,622	N=23,622	N=19,674
preDM (-) & preHTN (-)	19/12,272	1.00(ref)	1.00(ref)	1.00(ref)
preDM (-) & preHTN (+)	39/5841	4.17(2.41,7.21)	1.46(0.83,2.56)	1.51(0.83,2.77)
preDM(+) & preHTN (-)	12/2757	3.95(1.91,8.15)	1.21(0.58,2.54)	1.40(0.64,3.06)
preDM(+) & preHTN(+)	28/2752	8.54(4.76,15.32)	1.36(0.73,2.51)	1.70(0.88,3.27)

Notes: Data are HRs and 95% CI; model1, unadjusted; model2, adjusted for age and gender; model3, adjusted for age, gender, smoking, education, race, body mass index, cancer at baseline, total cholesterol, high-density-lipoprotein cholesterol, dietary energy intake, estimated glomerular filtration rate, the use of statin or antiplatelet drugs.

Abbreviations: DM, diabetes mellitus; HTN, hypertension; HR, hazard ratios; CI, confidence interval.

Table 3 Multivariate Cox Regression Analysis for Mortality in Different Models by Subgroups

All-Cause Mortality
HRs (95% CI)
		preDM (-)& preHTN (-)	preDM (-)& preHTN (+)	preDM(+)& preHTN (-)	preDM(+)& preHTN(+)
Subgroup	Cases/total					P-interaction
Age, y						0.128
≥65	413/1543	1.00(ref)	1.09(0.80,1.49)	0.96(0.64,1.44)	1.16(0.84,1.60)
55–64	142/1941	1.00(ref)	1.11(0.7,1.75)	1.09(0.61,1.94)	0.99(0.59,1.65)
≤54	484/20,138	1.00(ref)	1.02(0.8,1.31)	1.01(0.71,1.43)	1.49(1.09,2.05)
Gender						0.227
Male	648/11,233	1.00(ref)	1.02(0.82,1.27)	0.97(0.72,1.31)	1.13(0.89,1.45)
Female	391/12,389	1.00(ref)	1.04(0.78,1.37)	0.88(0.59,1.31)	1.28(0.92,1.80)
Race						<0.001
Non-white	534/13,235	1.00(ref)	1.11(0.87,1.40)	0.79(0.56,1.12)	0.98(0.74,1.32)
White	505/10,387	1.00(ref)	1.05(0.82,1.35)	1.16(0.83,1.61)	1.47(1.12,1.94)
BMI, kg/m^2						0.034
≥25	574/14,074	1.00(ref)	1.14(0.90,1.44)	1.08(0.80,1.47)	1.38(1.07,1.78)
<25	430/9337	1.00(ref)	0.92(0.71,1.20)	0.77(0.52,1.14)	0.91(0.66,1.26)
Smoking						0.760
Yes	593/8998	1.00(ref)	1.12(0.90,1.39)	1.13(0.84,1.51)	1.22(0.95,1.57)
No	388/11,971	1.00(ref)	0.95(0.72,1.25)	0.72(0.48,1.08)	1.21(0.88,1.67)
Low HDL-C						0.246
Yes	298/6840	1.00(ref)	1.02(0.74,1.41)	0.90(0.59,1.37)	1.12(0.79,1.59)
No	738/16,773	1.00(ref)	1.06(0.86,1.29)	0.97(0.73,1.29)	1.22(0.96,1.55)
Non-HDLC						0.627
≥130	664/13,236	1.00(ref)	1.08(0.87,1.34)	0.99(0.74,1.32)	1.30(1.03,1.64)
<130	372/10,377	1.00(ref)	0.95(0.71,1.28)	0.88(0.58,1.31)	0.90(0.61,1.31)

Cardiovascular mortality
HRs (95% CI)
		preDM (-)& preHTN (-)	preDM (-)& preHTN (+)	preDM(+)& preHTN (-)	preDM(+)& preHTN(+)
Subgroup	Cases/total					P-interaction
Age, y						0.359
≥65	58/1543	1.00(ref)	0.95(0.4,2.26)	1.03(0.35,3.00)	1.52(0.66,3.51)
55–64	13/1941	1.00(ref)	4.11(0.49,34.54)	3.41(0.3,38.9)	1.96(0.19,19.92)
≤54	27/20,138	1.00(ref)	2.09(0.81,5.41)	1.70(0.43,6.69)	1.50(0.37,6.17)
Gender						0.320
Male	65/11,233	1.00(ref)	1.51(0.73,3.13)	1.03(0.37,2.83)	1.57(0.72,3.42)
Female	33/12,389	1.00(ref)	1.37(0.46,4.14)	2.30(0.66,8.03)	2.04(0.61,6.91)
Race						0.029
Non-white	42/13,235	1.00(ref)	1.86(0.80,4.34)	1.09(0.32,3.66)	1.18(0.42,3.31)
White	56/10,387	1.00(ref)	1.42(0.60,3.39)	1.75(0.61,4.99)	2.27(0.94,5.49)
BMI, kg/m2						0.448
≥25	53/14,074	1.00(ref)	1.57(0.67,3.70)	1.87(0.68,5.12)	2.03(0.84,4.93)
<25	40/9337	1.00(ref)	1.36(0.58,3.23)	0.78(0.20,2.98)	1.11(0.40,3.09)
Smoking						0.780
Yes	59/8998	1.00(ref)	1.85(0.84,4.09)	1.34(0.47,3.86)	1.87(0.80,4.39)
No	39/11,971	1.00(ref)	1.14(0.43,2.97)	1.53(0.47,4.96)	1.54(0.53,4.44)
Low HDL-C						0.976
Yes	21/6840	1.00(ref)	1.23(0.38,4.01)	/	1.00(0.29,3.43)
No	77/16,773	1.00(ref)	1.71(0.84,3.46)	2.23(0.95,5.23)	2.07(0.95,4.49)
Non-HDLC						0.250
≥130	66/13,236	1.00(ref)	1.79(0.78,4.15)	2.43(0.92,6.42)	2.92(1.26,6.77)
<130	32/10,377	1.00(ref)	1.18(0.48,2.90)	0.45(0.09,2.22)	0.36(0.09,1.50)

Notes: Data are HRs and 95% CI; Adjusted for age, gender, smoking, education, race, body mass index, cancer at baseline, total cholesterol, high-density-lipoprotein cholesterol, energy intake, estimated glomerular filtration rate, the use of statin, antiplatelet drugs.

Abbreviations: DM, diabetes mellitus; HTN, hypertension; HR, hazard ratios; CI, confidence interval; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol.