Online supplement
CONTRASTING
MORTALITY
RISKS
AMONG
SUBGROUPS
OF
TREATED
HYPERTENSIVE PATIENTS DEVELOPING NEW-ONSET DIABETES
*Stefanie Lip, *Panniyammakal Jeemon, Linsay McCallum, Anna F Dominiczak, Gordon T
McInnes, Sandosh Padmanabhan
*Equal contributions
Institute of Cardiovascular and Medical Sciences (ICAMS), University of Glasgow, Glasgow,
Scotland, United Kingdom.
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Supplementary Methods
Study setting and study population
In brief, patients are referred to the GBPC if blood pressure is not well-controlled in primary
care or if there is evidence of high risk such as early onset hypertension, family history of
CVD or premature CVD. Structured instruments are used to collect information from all
patients attending the clinic and these data are stored electronically in a single computerised
database, which contains information on 16,011 patients attending the clinic from 1969 until
2011. The West of Scotland research ethics service (WoSRES) of the National Health Service
has approved the study of the GBPC database (11/WS/0083).
Clinical measurements
The GBPC employs specialist hypertension nurses who are experienced and highly trained in
BP and other clinical measurements. At each visit, three BP measurements are performed,
one minute apart, and the mean of the second and third measurements is recorded. Height and
weight of all patients are measured using standardised equipment during each visit in order to
calculate BMI. Blood samples are collected at baseline and at regular intervals for estimation
of routine haematological and biochemical indices in the blood pressure clinic. In addition all
the blood investigation results from other hospital encounters were obtained through
electronic record linkage. All biochemical investigations are performed at the Western
Infirmary clinical laboratory service. Both smoking (any versus none) and alcohol use
(quantity and frequency of consumption) are assessed using a structured format during the
clinic visit. Data on refilled prescriptions are available on a subset of patients through the
Information Services Division (ISD) for NHS Scotland. The Prescribing Information System
holds information on 100% of NHS Scotland prescriptions dispensed within the community
and claims for payment by a pharmacy contractor (i.e. pharmacy, dispensing doctor or
appliance supplier). Prescription data is routinely entered in the database by the treating
physicians and pharmacy-refill prescription records are available from 2004 onwards on all
living subjects.
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Table S1: Baseline characteristics of study population
Total
Women
Variables
(N=15,089)
Men (n=7,114)
(n=7,975)
Age in years, mean (SD)
50.92 (14.68)
49.99 (13.47)
51.75 (15.63)
Body Mass Index in kg/m2, mean (SD)
27.77 (5.84)
27.77 (5.24)
27.77 (6.32)
Smoking, n (%) †
6103 (44.34)
3149 (48.79)
2954 (40.40)
Alcohol use, n (%)‡
7839 (58.91)
4643 (74.40)
3196 (45.22)
SBP in mmHg, mean (SD)
162.71 (28.46)
161.07 (26.46)
164.19 (30.05)
DBP in mmHg, mean (SD)
96.51 (19.74)
97.42 (14.79)
95.72 (23.27)
Prevalent Diabetes, n (%)
654 (4.33)
341 (4.79)
313 (3.92)
Plasma glucose in mmol/l, mean (SD)
5.83 (2.20)
5.97 (2.44)
5.70 (1.94)
CKD (eGFR<60), n (%)
2909 (23.32)
1070 (18.07)
1839 (28.07)
Ischemic heart disease, n (%)
2387 (16.93)
1275 (19.22)
1112 (14.90)
Total cholesterol in mmol/l, mean (SD)
5.92 (1.46)
5.82 (1.56)
6.02 (1.34)
SBP=Systolic blood pressure, DBP=Diastolic blood pressure, SD=Standard deviation, IQR=Inter quartile range, eGFR=estimated glomerular
filtration rate, CKD=Chronic kidney disease. †Data missing in 1,334 individuals, ‡Data missing in 1,794 individuals
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Table S2. Characteristics of study population in individuals who developed new onset diabetes early before 10 years) and late (after 10 years)
during the follow-up period.
Variables
Early NOD (n=705)
Late NOD (n=1157)
P value
Age in years, mean (SD)
54.04 (12.69)
47.18 (10.79)
<0.001
Age at NOD in years, mean (SD)
60.14 (12.70)
65.92 (10.82)
<0.001
Time to NOD in years, median (IQR)
6.02 (4.04-8.17)
17.86 (13.44-23.15)
<0.001
Women, n (%)
334 (47.38)
549 (47.45)
0.98
Body Mass Index in Kg/m2, mean (SD)
32.12 (7.14)
29.42 (5.41)
<0.001
Smoking, n (%)
316 (45.40)
521 (45.19)
0.93
Alcohol use, n (%)
308 (45.70)
732 (64.44)
<0.001
Systolic Blood Pressure in mmHg, mean (SD)
162.61 (26.42)
165.73 (27.36)
0.016
Diastolic Blood Pressure in mmHg, mean (SD)
95.80 (13.58)
99.67 (14.79)
<0.001
Plasma Glucose, mmol/l
7.63 (4.28)
6.24 (2.33)
<0.001
eGFR<60, n (%)
184 (28.40)
156 (14.99)
<0.001
Ischemic heart disease, n (%)
164 (23.43)
213 (18.41)
0.005
Total cholesterol in mmol/l, mean (SD)
5.86 (1.34)
6.29 (1.29)
<0.001
NOD=new onset diabetes, SD=standard deviation, IQR=inter quartile range, eGFR=estimate glomerular filtration rate.
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Table S3: Cox model for predictors of new onset diabetes
Variables
HR (95% CI)
P Value
Age in years
1.02 (1.01-1.03)
<0.001
Women
0.68 (0.60-0.76)
<0.001
Alcohol Use
0.77 (0.67-0.90)
<0.001
Smoking
1.20 (1.04-1.37)
0.02
Cholesterol (per SD increase)
0.97 (0.91-1.01)
0.16
(per SD increase)
1.30 (1.25-1.34)
<0.001
Systolic Blood Pressure (per SD increase)
1.12 (1.02-1.22)
0.005
CKD (eGFR<60)
0.87 (0.73-1.02)
0.13
Ischemic heart disease
1.15 (1.02-1.31)
0.03
Glucose (per SD increase)
1.44 (1.38-1.50)
<0.001
Body Mass Index
SD=Standard deviation, HR=Hazard ratio, CI=Confidence interval, CKD=Chronic Kidney
Disease.
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Table S4. Drug use and incidence of diabetes
Drugs
NOD (n=61)
NonDM (n=2,013)
P value
ACE Inhibitors (ACEI), n (%)
47 (77.05)
1,342 (66.65)
0.089
Duration ACE, Median (IQR)
1,310 (488-1919)
1,158 (185-2,162)
0.835
Angiotensin receptor blockers (ARB), n (%)
24 (39.34)
890 (44.23)
0.446
Duration ARB, Median (IQR)
944 (686-1767)
1,585 (641-2436)
0.188
Beta Blockers (BB), n (%)
28 (45.90)
1,112 (55.24)
0.149
Duration BB, Median (IQR)
1,248 (715-2177)
1,401 (275-2801)
0.612
Calcium channel blockers, n (%)
48 (78.69)
1,370 (68.09)
Duration CCB, Median (IQR)
1,034 (457-1858)
1,462 (549-2344)
0.034
Thiazide like diuretic (TZ), n (%)
35 (57.38)
1,159 (57.60)
0.969
Duration Thiazide, Median (IQR)
943 (396-1707)
1,507 (548-2586)
0.038
Alpha blockers, n (%)
11 (18.03)
476 (23.66)
0.304
Duration Alpha B, Median (IQR)
1,827 (123-2466)
762 (62-1766)
0.278
Spironolactone, n (%)
5 (8.20)
237 (11.77)
0.391
Duration Spironolactone, Median (IQR)
1,219 (1096-1462)
578 (122-1521)
0.089
Beta blocker + Thiazide
46 (75.41)
1,562 (77.63)
0.08
0.68
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Number of anti-hypertensive drugs, median (IQR)
3 (2-4)
3 (2-5)
0.947
NOD=New-onset diabetes, NonDM=non diabetic, IQR=inter quartile range, BB=beta blockers, TZ=thiazide like diuretic, ARB=angiotensin receptor
blockers, ACEI=angiotensin converting enzyme inhibitors.
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Table S5. Predictors of early onset diabetes
Predictors of Early NOD
HR (95% CI)
P value
Age in years, per 5 year increase
1.18 (1.14-1.23)
<0.001
Women
0.74 (0.61-0.90)
0.002
Alcohol Use
0.79 (0.66-0.96)
0.017
Smoking
1.08 (0.90-1.29)
0.396
Cholesterol (per SD increase)
0.82 (0.74-0.91)
<0.001
Body Mass Index (per SD increase)
1.41 (1.35-1.46)
<0.001
Systolic Blood Pressure (per SD increase)
1.06 (0.96-1.17)
0.263
eGFR<60
1.43 (1.16-1.77)
0.001
Ischaemic heart disease
1.40 (1.15-1.71)
<0.001
Glucose (per SD increase)
1.19 (1.16-1.21)
<0.001
NOD=new onset diabetes, SD=standard deviation, eGFR=estimated glomerular filtration
rate, HR=hazard ratio, CI=confidence interval.
8
Table S6. Cox model for diabetes with mortality risk estimated from onset of diabetes
Non-CVM
Variables
ACM (N=2380)
CVM (N=1168)
(N=1212)
Early NOD
1.20 (1.03-1.41)*
1.25 (1.01-1.57)*
1.15 (0.92-1.45)
Late NOD
0.54 (0.47-0.63)*
0.47 (38-0.58)*
0.62 (0.50-0.75)*
Prevalent DM
1.74 (1.41-2.14)*
1.99 (1.49-2.66)*
1.53 (1.13-2.06)*
Early NOD (allowing a minimum of 11 years of follow-up) †
1.24 (1.05-1.46)*
1.30 (1.03-1.62)*
1.18 (0.93-1.49)
Late NOD (allowing a minimum of 11 years of follow-up) †
0.53 (0.46-0.62)*
0.48 (0.38-0.59)*
0.60 (0.49-0.74)*
Prevalent DM (allowing a minimum of 11 years of follow-up) † 1.83 (1.46-2.29)*
2.18 (1.61-2.93)*
1.51 (1.07-2.12)*
NOD=New onset diabetes, Prevalent DM=Prevalent diabetes, ACM=All-cause mortality, CVM=Cardiovascular disease mortality, Non-CVM=Noncardiovascular disease mortality. †ACM=2258, CVM=1125, Non-CVM=1133. *p<0.05
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10
15
20
25
30
35
40
Figure S1: Distribution of body mass index stratified by diabetes status
noNOD
NonDM
earlyNOD
lateNOD
DM
10
0
2
4
6
8
10
12
14
16
Figure S2: Distribution of random blood glucose stratified by diabetes status
noNOD
Non
DM
earlyNOD
lateNOD
DM
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