Participants’ characteristics
We identified 268 patients who met our inclusion criteria (Fig.1). The age range of population was 36 to 76 years, the mean age were 58.15±9.17 years. The study population included 208 men (77.6%) and 60 women (22.4%). Table 1 presents the characteristics of the participants. There were 110 subjects (41%) with a physical activity lifestyle and 158 (59.0%) with an inactivity lifestyle. In the regular physical activity group, the mean age was 55.89±8.68 years, with a mean BMI of 24.50±2.41 and the percentages of males were 78 (70.6%).
Meanwhile, compared with those in the inactivity group, those with a regular physical activity lifestyle had significantly younger age. We observed that patients with regular physical activity lifestyle had significantly lower levels of Scr, uric acid, cholesterol, LDL-C, and m-Alb/Cr. We also observed that the proportion of smoking, drinking and family history of hypertension was similar in the two groups.
Table 1 Baseline characteristics of participants
|
Total (N=268)
|
Physical activity (N=110)
|
Inactivity (N=158)
|
P value
|
Age (years)
|
58.15±9.17
|
55.89±8.68
|
59.77±9.20
|
0.001**
|
Gender (Female n,%)
|
60 (22.4%)
|
32 (29.1%)
|
28 (17.7%)
|
0.037*
|
BMI (kg/m2)
|
25.95±12.21
|
24.50±2.41
|
26.92±15.74
|
0.113
|
SBP (mmHg)
|
126.21±8.62
|
125.00±8.697
|
127.04±8.49
|
0.057
|
DBP (mmHg)
|
78.41±7.91
|
77.68±8.60
|
78.92±7.39
|
0.207
|
Years of T2DM (n,%)
|
|
|
|
0.555
|
<5 years
|
187 (70.03%)
|
80 (72.7%)
|
108 (68.4%)
|
|
5-10 years
|
63 (23.60%)
|
25 (22.7%)
|
38 (24.1%)
|
|
≥10years
|
17 (6.37%)
|
5 (4.6%)
|
12 (7.6%)
|
|
HbA1C (%)
|
7.56±1.55
|
7.66±1.74
|
7.49±1.42
|
0.392
|
FPG (mmol/L)
|
7.47±2.47
|
7.60±2.78
|
7.40±2.24
|
0.509
|
ALT (IU/L)
|
28.32±30.62
|
27.36±21.23
|
29.02±35.91
|
0.666
|
Scr (mmol/L)
|
69.07±24.70
|
65.11±11.41
|
71.68±30.50
|
0.033*
|
Uric acid (mmol/L)
|
342.62±88.04
|
326.00±84.56
|
353.82±89.35
|
0.011*
|
K+ (mmol/L)
|
3.91±0.33
|
3.92±0.30
|
3.91±0.36
|
0.825
|
Na+ (mmol/L)
|
145.70±76.81
|
141.04±2.13
|
140.97±2.37
|
0.798
|
Cl- (mmol/L)
|
104.49±2.53
|
104.80±2.35
|
104.27±2.64
|
0.092
|
Ca2+ (mmol/L)
|
2.34±0.10
|
2.35±0.10
|
2.34±0.10
|
0.830
|
P3+ (mmol/L)
|
1.18±0.17
|
1.19±0.17
|
1.18±0.17
|
0.474
|
Triglycerides (mmol/L)
|
2.25±2.07
|
2.04±1.34
|
2.40±2.45
|
0.157
|
Total Cholesterol (mmol/L)
|
4.20±1.23
|
4.07±1.27
|
4.40±1.14
|
0.031*
|
HDL-C (mmol/L)
|
1.08±0.27
|
1.12±0.30
|
1.05±0.26
|
0.051
|
LDL-C (mmol/L)
|
2.41±0.91
|
2.30±0.91
|
2.56±0.90
|
0.021*
|
m-Alb/Cr
|
7.75±22.42
|
3.99±9.08
|
10.41±26.47
|
0.015*
|
CRP (mg/L)
|
3.66±5.95
|
4.07±8.67
|
3.43±3.57
|
0.591
|
Free T3 (pg/ml)
|
3.33±0.45
|
3.34±0.41
|
3.31±0.46
|
0.652
|
Free T4 (ng/dl)
|
0.89±0.16
|
0.90±0.19
|
0.89±0.13
|
0.531
|
Total T3 (ng/ml)
|
0.88±0.17
|
0.88±0.17
|
0.88±0.17
|
0.971
|
Total T4 (ug/dl)
|
7.89±1.45
|
7.88±1.49
|
7.92±1.34
|
0.859
|
TSHu (IU/ml)
|
1.93±1.12
|
1.80±1.07
|
2.02±1.11
|
0.102
|
PTH (pg/ml)
|
43.20±23.81
|
41.79±8.58
|
44.36±20.54
|
0.218
|
Thyroid nodule (n, %)
|
138 (51.5%)
|
58 (52.7%)
|
80 (50.6%)
|
0.804
|
Smoking (n, %)
|
85 (31.7%)
|
37 (33.6%)
|
48 (30.4%)
|
0.344
|
Drinking (n, %)
|
64 (23.9%)
|
24 (21.8%)
|
40 (25.3%)
|
0.265
|
Depression/anxiety (n, %)
|
7 (2.6%)
|
3 (2.7%)
|
4 (2.5%)
|
>0.05
|
Sleep disorders (n, %)
|
16 (6.0%)
|
7 (6.4%)
|
9 (5.7%)
|
0.800
|
Family history of hypertension (n, %)
|
52 (19.4%)
|
21 (19.1%)
|
31 (19.6%)
|
>0.05
|
Note: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; T2DM, type 2 Diabetes Mellitus; HbA1C, glycosylated hemoglobin A1c; FPG, fast plasma glucose; ALT, alanine aminotransferase; Scr, Serum creatinine; HDL-C, high density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; m-Alb/Cr: the ratio of urinary micro albumin to creatinine; CRP, C-reactive protein; PTH, parathyroid hormone.
Newly-onset hypertension and related CVDs
As is showed in table 2, during 5 years of follow-up, we recorded a total of 145 coronal AS, which included 46 (42.7%) in the regular physical activity group and 98 (62%) in the physical inactivity group, the risk of coronal AS was obviously lower in the regular physical activity group, compared to the inactivity group (p<0.01). The total prevalence of CHD in this retrospective cohort was 39.9%. Compared to those in the inactivity group, patients in the regular physical activity group had a significantly lower incidence of CHD (30% vs 46.8%, p<0.01). In addition, we observed that the incidence of hypertension had significantly difference in the two groups, patients in the regular physical activity group had significantly lower incidence than those in the inactivity group (15.5% vs 35.4%, p<0.01). We also observed that the incidence of carotid/femoral AS was lower in the regular physical activity group than in the inactivity group, though it had no significance (49.5% vs 61.1%, p=0.051). However, there was no significant difference in terms of the incidence of cerebral ischemic focus, percutaneous coronary intervention (PCI), and myocardial bridge.
Table 2 Newly onset hypertension and related CVDs during follow-up period
|
Total (N=268)
|
Physical activity (N=110)
|
Inactivity (N=158)
|
P value
|
Femoral/carotid AS (n, %)
|
150 (56.2%)
|
54 (49.5%)
|
96 (61.1%)
|
0.051
|
Coronary AS (n, %)
|
145 (54.1%)
|
46 (42.7%)
|
98 (62%)
|
0.002**
|
Cerebral ischemic focus (n, %)
|
66 (24.6%)
|
24 (21.8%)
|
42 (26.6%)
|
0.591
|
CHD (n, %)
|
107 (39.9%)
|
33 (30%)
|
74 (46.8%)
|
0.006**
|
Hypertension (n, %)
|
73 (27.2%)
|
17 (15.5%)
|
56 (35.4%)
|
0.000**
|
PCI (n, %)
|
61 (22.8%)
|
19 (18.2%)
|
41 (25.9%)
|
0.142
|
Coronary artery bypass graft (n, %)
|
18 (6.7%)
|
6 (5.5%)
|
12 (7.6%)
|
0.622
|
Note: CVDs, cardiovascular diseases; AS, atherosclerosis; CHD, coronary heart disease; PCI, percutaneous coronary intervention.
Univariate and multivariate logistic regressions for new-onset hypertension in pre-hypertension patients with T2DM
Unadjusted and adjusted ORs for new-onset hypertension of the whole cohort are shown in Table3. The univariate and multivariate analysis showed that BMI (univariate: OR 1.126, 95% CI: 0.504 to 1.842, P<0.05; multivariate: OR 1.138, 95% CI: 1.019 to 1.272, p<0.05), HbA1C (univariate: OR=1.129, 95% CI: 1.016–1.253,P<0.05; multivariate: OR 1.206, 95% CI: 1.006 to 1.446, p<0.05), and physical exercise (univariate: OR 0.333, 95% CI: 0.181 to 0.613, P<0.01; multivariate: OR 0.337, 95% CI: 0.168 to 0.677, p<0.01), were independently associated with new-onset hypertension in T2DM patients.
Table 3 Univariate and multivariate ORs for new-onset hypertension in pre-hypertension T2DM participants
Variables
|
Univariate
|
Multivariate
|
OR (95%CI)
|
P-Value
|
OR (95%CI)
|
P-Value
|
Age
|
1.029 (0.998-1.060)
|
0.067
|
1.032 (0.990-1.076)
|
0.136
|
Gender (Female)
|
0.963 (0.504-1.842)
|
0.910
|
1.739 (0.729-4.146)
|
0.212
|
BMI
|
1.126 (1.023-1.240)
|
0.015 *
|
1.138 (1.019-1.272)
|
0.022 *
|
FPG
|
1.121 (0.945-1.331)
|
0.190
|
0.971 (0.724-1.302)
|
0.845
|
Scr
|
1.008 (0.997-1.018)
|
0.159
|
1.012 (0.999-1.024)
|
0.070
|
Triglycerides
|
1.033 (0.913-1.169)
|
0.604
|
0.940 (0.806-1.097)
|
0.434
|
Total cholesterol
|
1.108 (0.891-1.378)
|
0.358
|
1.242 (0.939-1.643)
|
0.128
|
HbA1C
|
1.129 (1.016-1.253)
|
0.024 *
|
1.206 (1.006-1.446)
|
0.043 *
|
Years of diabetes
|
1.052 (0.972-1.138)
|
0.206
|
1.051 (0.952-1.159)
|
0.325
|
Drinking
|
1.571 (0.858-2.879)
|
0.143
|
1.551 (0.731-3.291)
|
0.253
|
Smoking
|
1.172 (0.662-2.074)
|
0.586
|
1.171 (0.569-2.407)
|
0.668
|
Regular physical activity
|
0.333 (0.181-0.613)
|
<0.001**
|
0.337 (0.168-0.677)
|
0.002**
|
Note:T2DM, type 2 Diabetes Mellitus; BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.
Univariate and multivariate logistic regressions for new-onset hypertension in the subgroup analysis by BMI
To further identify the impact of baseline overweight on the risk of new-onset hypertension in pre-hypertension patients with T2DM, univariate and multivariate logistic regressions analysis was performed (Table 4). We defined overweight as BMI ≥25 kg/m2 and used this to subdivide the T2DM patients into an overweight group (n=142) and a non-overweight group (n=126). In the overweight group, univariate logistic regression analysis found that the risk of new-onset hypertension was significantly associated with age (OR 1.041; 95% CI 1.001 to 1.083; p<0.05) and regular physical exercise (OR 0.219; 95% CI 0.085 to 0.567; p<0.01). And we found that regular physical exercise (OR 0.187; 95% CI 0.063 to 0.558; p<0.01) remained as the protective factor for new-onset hypertension in the multivariate logistic regressions analysis. In the non- overweight group, there was no significantly association between regular physical exercise and new-onset hypertension in T2DM patients.
Table 4 Univariate and multivariate ORs for new-onset hypertension in the Subgroup by BMI
Variables
|
Univariate
|
Multivariate
|
OR (95%CI)
|
P-Value
|
OR (95%CI)
|
P-Value
|
BMI<25 (N=126)
|
Age
|
1.021 (0.972-1.073)
|
0.403
|
1.026 (0.956-1.100)
|
0.482
|
Gender (Female)
|
1.268 (0.509-3.156)
|
0.610
|
4.043 (0.923-17.716)
|
0. 064
|
FPG
|
1.092 (0.938-1.270)
|
0.256
|
1.173 (0.867-1.586)
|
0.302
|
Scr
|
1.004 (0.992-1.016)
|
0.490
|
1.014 (1.000-1.029)
|
0.046 *
|
Triglycerides
|
1.104 (0.927-1.315)
|
0.267
|
0.992 (0.774-1.270)
|
0.947
|
Total cholesterol
|
1.457 (1.054-2.015)
|
0.023 *
|
1.611 (1.012-2.565)
|
0.045 *
|
HbA1C
|
1.014 (0.778-1.320)
|
0.920
|
0.764 (0.468-1.249)
|
0.283
|
Years of diabetes
|
0.199 (0.967-1.249)
|
0.150
|
1.100 (0.940-1.289)
|
0.235
|
Drinking
|
3.036 (1.140-8.086)
|
0.026 *
|
2.695 (0.702-10.347)
|
0.149
|
Smoking
|
2.035 (0.834-4.963)
|
0.118
|
4.149 (1.106-15.561)
|
0.035 *
|
Regular physical activity
|
0.573 (0.242-1.359)
|
0.206
|
0.627 (0.217-1.812)
|
0.389
|
BMI≥25 (N=142)
|
Age
|
1.041 (1.001-1.083)
|
0.044 *
|
1.039 (0.984-1.096)
|
0.170
|
Gender (Female)
|
0.897 (0.341-2.361)
|
0.826
|
1.980 (0.514-7.625)
|
0.231
|
FPG
|
1.158 (0.995-1.348)
|
0.059
|
1.298 (0.997-1.691)
|
0.053
|
Scr
|
1.016 (0.996-1.037)
|
0.113
|
1.023 (0.996-1.051)
|
0.101
|
Triglycerides
|
0.954 (0.789-1.154)
|
0.629
|
0.924 (0.739-1.155)
|
0.487
|
Total cholesterol
|
0.864 (0.632-1.178)
|
0.356
|
1.051 (0.713-1.549)
|
0.802
|
HbA1C
|
1.207 (0.958-1.521)
|
0.110
|
1.076 (0.722-1.605)
|
0.718
|
Years of diabetes
|
1.028 (0.930-1.135)
|
0.594
|
0.987 (0.865-1.126)
|
0.847
|
Drinking
|
0.957 (0.439-2.083)
|
0.911
|
1.374 (0.511-3.692)
|
0.529
|
Smoking
|
0.763 (0.359-1.619)
|
0.480
|
0.726 (0.274-1.926)
|
0.520
|
Regular physical activity
|
0.219 (0.085-0.567)
|
0.002**
|
0.187 (0.063-0.558)
|
0.003**
|
Note: BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.
Univariate and multivariate logistic regressions for new-onset hypertension in the subgroup analysis by HbA1C
HbA1C level is utilized clinically as an indicator of the adequacy of glycemic control over several months prior to testing. To explore the impact of baseline HbA1C on the risk of new-onset hypertension in the T2DM patients, we performed subgroup analysis according to HbA1C level. The American Diabetes Association has recommended that an HbA1C breakpoint of 7% would realize the greatest cardiovascular benefit [22]. As is showed in Table 5, our results revealed that in the glucose well controlled group (HbA1C<7%), regular physical exercise (OR=0.309, 95% CI: 0.114-0.834, p<0.05) was associated with the incidence of new-onset hypertension in T2DM patients. After adjusting for confounding factors, regular physical exercise (OR=0.385, 95% CI: 0.118-1.261, p=0.115) was no longer the related factor. In the glucose poorly controlled group (HbA1C³7%), both univariate and multivariate analysis suggested that regular physical exercise (univariate: OR 0.349; 95% CI 0.160 to 0.760; p<0.01; multivariate: OR 0.349; 95% CI 0.138 to 0.880; p<0.05) was the independent associated factor of the incidence of new-onset hypertension in T2DM patients.
Table 5 Univariate and multivariate ORs for new-onset hypertension in the subgroup by HbA1C level
Variables
|
Univariate
|
Multivariate
|
OR (95%CI)
|
P-Value
|
OR (95%CI)
|
P-Value
|
HbA1C level<7 (N=111)
|
|
|
|
|
Age
|
1.070 (1.019-1.124)
|
0.007 **
|
1.087 (1.008-1.172)
|
0.029 *
|
Gender (Female)
|
0.936 (0.349-2.512)
|
0.896
|
0.959 (0.241-3.818)
|
0.953
|
BMI
|
1.036 (0.890-1.206)
|
0.646
|
1.112 (0.907-1.362)
|
0.308
|
Glucose
|
0.999 (0.703-1.418)
|
0.994
|
0.941 (0.603-1.469)
|
0.789
|
Scr
|
1.006 (0.994-1.019)
|
0.302
|
1.006 (0.993-1.020)
|
0.354
|
Triglyceride
|
1.049 (0.766-1.436)
|
0.765
|
1.023 (0.684-1.530)
|
0.911
|
Cholesterol
|
1.178 (0.805-1.724)
|
0.398
|
1.816 (1.048-3.148)
|
0.034 *
|
Years of diabetes
|
1.163 (1.036-1.304)
|
0.010 *
|
1.094 (0.951-1.260)
|
0.210
|
Drinking
|
1.227 (0.486-3.098)
|
0.665
|
1.081 (0.319-3.659)
|
0.901
|
Smoking
|
1.255 (0.511-3.084)
|
0.620
|
1.422 (0.423-4.779)
|
0.569
|
Regular physical activity
|
0.309 (0.114-0.834)
|
0.020 *
|
0.385 (0.118-1.261)
|
0.115
|
HbA1C level³7 (N=157)
|
|
|
|
|
Age
|
1.000 (0.962-1.040)
|
>0.05
|
1.016(0.963-1.072)
|
0.566
|
Gender (Female)
|
0.982 (0.415-2.320)
|
0.967
|
2.656 (0.793-8.900)
|
0.113
|
BMI
|
1.1195 (1.053-1.357)
|
0.006 **
|
1.193 (1.033-1.033)
|
0.017 *
|
Glucose
|
1.218 (1.064-1.393)
|
0.004 **
|
1.304 (1.096-1.550)
|
0.003 **
|
Scr
|
1.010 (0.991-1.030)
|
0.296
|
1.024 (0.998-1.051)
|
0.067
|
Triglyceride
|
1.035 (0.902-1.186)
|
0.625
|
0.946 (0.793-1.129)
|
0.540
|
Cholesterol
|
1.080 (0.825-1.414)
|
0.575
|
1.096 (0.763-1.574)
|
0.620
|
Years of diabetes
|
0.942 (0.832-1.067)
|
0.350
|
0.949 (0.819-1.101)
|
0.492
|
Drinking
|
1.895 (0.849-4.228)
|
0.118
|
2.503 (0.887-7.070)
|
0.083
|
Smoking
|
1.126 (0.536-2.362)
|
0.754
|
0.815 (0.303-2.188)
|
0.684
|
Regular physical activity
|
0.349 (0.160-0.760)
|
0.008 **
|
0.349 (0.138-0.880)
|
0.026 *
|
Note: BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.