the recent introduction of drug-eluting stents in interventional ... · web viewthe recent...
TRANSCRIPT
Online Appendix
Online Table 1. Baseline Characteristics of All KNHANES Participants and Those Included in
Study Population vs. Those Excluded.a
Variable
All KNHANES
Participants
(N=41,321)
Included Study
Participants
(N=13,346)
Excluded
Participants
(N=27,975)
Age
Median (IQR), y 49 (36-63) 63 (53-72) 41 (32-53)
< 60 years 28,525 (69.0) 5,233 (39.2) 23,292 (83.3)
≥ 60 years 12,796 (31.0) 8,113 (60.8) 4,683 (16.7)
Male sex 17,908 (43.3) 6,081 (45.6) 11,827 (42.3)
Systolic blood pressure, mm Hg 117 (106-130) 135 (129-144) 110 (102-118)
Diastolic blood pressure, mm Hg 75 (69-82) 82 (74-90) 72 (68-79)
Heart rate, beats/min 56 (54-58) 56 (53-58) 56 (54-58)
Diabetes mellitusb 3,911/36,594 (10.7) 2,615 (19.6) 1,296/23,248 (5.6)
Fasting glucose level, mg/dl 93 (87-101) 98 (91-110) 91 (86-97)
Chronic kidney diseasec 1,537/37,912 (4.1) 1,136 (8.5) 401/24,566 (1.6)
Glomerular filtration rate,
mL/min/1.73 m287 (76-98) 81 (71-91) 90 (80-101)
Current smoking 7,824/37,886 (20.7) 2,271 (17.0) 5,553/24,540 (22.6)
Hyperlipidemiad 4,668/36,346 (12.8) 2,611 (19.6) 2,057/23,000 (8.9)
Total cholesterol, mg/dl 185 (163-210) 191 (168-216) 183 (161-207)
Obesity
BMI ≥ 25, no. (%)e 12,175/39,058 (31.2) 5,732 (42.9) 6,443/25,712 (25.1)
BMI ≥ 30, no. (%) 1,509/39,058 (3.9) 792 (5.9) 717/25,712 (2.8)
Prevalent cardiovascular diseasef 1,653/38,560 (4.3) 1,198 (9.0) 455/25,214 (1.8)
Receiving antihypertensive agents 7,389/38,560 (19.2) 7,373 (55.2) 16/25,214 (0.1)
Framingham risk score
<10% 27,365/36,330 (75.3) 7,272 (54.5) 20,093/22,984 (87.4)
10-20% 6,385/36,330(17.6) 3,977 (29.8) 2,408/22,984 (10.5)
>20% 2,580/36,330 (7.1) 2,097 (15.7) 483/22,984 (2.1)
Abbreviations: BMI, body mass index; KNHANES, Korea National Health and Nutrition
Examination Surveys.a Data are expressed as median (interquartile range) or number (%).b Diabetes mellitus was defined as a fasting glucose level higher than 126 mg per deciliter or
current use of antidiabetic drugs or by physician’s diagnosis. c Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 mL/min/1.73
m2
d Hyperlipidemia was defined as a total cholesterol level of 240 mg/dl or more or receiving statin
therapy.e The BMI is the weight in kilograms divided by the square of the height in meters.f Cardiovascular disease includes coronary heart disease, angina, and stroke.
2
Online Table 2. Comparison of Characteristics and Risk Factor Profiles of the KNAHNES Sample with Hypertension and Those
Who Meet or Not Meet BP Goals According to the SPRINT Criteria and the 2014 BP Guideline.a
Variable
All Adults with
Hypertension
(N=13,346) Status of BP Controlb P Value
Below SPRINT BP
Goal
(N=1,677)
Above SPRINT BP
Goal, but below 2014
Guideline BP Goal
(N=7,914)
Above 2014
Guideline BP Goal
(N=3,755)
Age
Median (IQR), y 63 (53-72) 65 (57-73) 63 (53-72) 62 (52-72) <0.001
< 60 years 5,233 (39.2) 539 (32.1) 2,960 (37.4) 1,734 (46.2) <0.001
≥ 60 years 8,113 (60.8) 1,138 (67.9) 4,954 (62.6) 2,021 (53.8) <0.001
Male sex 6,081 (45.6) 728 (43.4) 3,667 (46.3) 1,686 (44.9) 0.06
Systolic blood pressure, mm Hg 135 (129-144) 113 (108-116) 133 (130-138) 151 (144-160) <0.001
Diastolic blood pressure, mm Hg 82 (74-90) 71 (66-77) 81 (75-89) 90 (80-97) <0.001
Heart rate, beats/min 56 (53-58) 56 (52-58) 56 (53-58) 56 (54-64) 0.02
Diabetes mellitusc 2,615 (19.6) 449 (26.8) 1,230 (15.5) 936 (24.9) <0.001
Fasting glucose level, mg/dl 98 (91-110) 99 (91-114) 97 (91-108) 100 (92-113) <0.001
Chronic kidney diseased 1,136 (8.5) 221 (13.2) 490 (6.2) 425 (11.3) <0.001
Glomerular filtration rate,
mL/min/1.73 m2
81 (71-91) 77 (68-87) 82 (71-92) 81 (70-92) <0.001
Current smoking 2,271 (17.0) 289 (17.2) 1,322 (16.7) 660 (17.6) 0.49
Hyperlipidemiae 2,611 (19.6) 402 (24.0) 1,486 (18.8) 723 (19.3) <0.001
Total cholesterol, mg/dl 191 (168-216) 183 (159-206) 191 (16-216) 195 (171-220) <0.001
Obesity
BMI ≥ 25, no. (%)f 5,732 (42.9) 764 (45.6) 3,312 (41.8) 1,656 (44.1) 0.005
BMI ≥ 30, no. (%) 792 (5.9) 101 (6.0) 455 (5.7) 236 (6.3) 0.51
Prevalent cardiovascular diseaseg 1,198 (9.0) 239 (14.3) 647 (8.2) 312 (8.3) <0.001
Receiving antihypertensive agents 7,373 (55.2) 1,669 (99.5) 4,071 (51.4) 1,633 (43.5) <0.001
Framingham risk score <0.001
<10% 7,272 (54.5) 1,163 (69.4) 4,334 (54.8) 1,775 (47.3)
10-20% 3,977 (29.8) 412 (24.6) 2,397 (30.3) 1,168 (31.1)
>20% 2,097 (15.7) 102 (6.1) 1,183 (14.9) 812 (21.6)
Abbreviations: BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; KNHANES, Korea National Health and
Nutrition Examination Surveys.
4
a Data are expressed as median (interquartile range) or number (%).b BP target used in the SPRINT criteria was defined as systolic BP <120 mm Hg (1) and those used in the 2014 hypertension
guidelines were defined as BP <140/90 mm Hg in ages 18-59 years without CKD or diabetes, BP <150/90 mm Hg in ages ≥60 years
without CKD or diabetes, BP <140/90 mm Hg in CKD, and BP <140/90 mm Hg in diabetes (2).c Diabetes mellitus was defined as a fasting glucose level higher than 126 mg per deciliter or current use of antidiabetic drugs or by
physician’s diagnosis. d Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2
e Hyperlipidemia was defined as a total cholesterol level of 240 mg/dl or more or receiving statin therapy.f The BMI is the weight in kilograms divided by the square of the height in meters.g Cardiovascular disease includes coronary heart disease, angina, and stroke.
5
Online Table 3. Standardized Event Rates and Hazard Ratios for Adverse Cardiovascular Events According to Status of BP Control
Based On the SPRINT and JNC 7 Guideline Among Adults with Hypertension in the NHIS Health Examinee Cohort.
All Adults with
Hypertension
(N=67,965) Status of BP Control Levelsa
P for
Trend
Variable
Below SPRINT BP
Goal
(N=5,639)
Above SPRINT BP
Goal, but below JNC 7
BP Goal
(N=37,494)
Above JNC 7
BP Goal
(N=24,832)
Major cardiovascular eventsb
No. of events 1,158 99 484 575
Rate (95% CI)c 2.60 (2.45-2.75) 2.53 (2.08-3.08) 2.29 (2.10-2.51) 3.08 (2.84-3.34)
Hazard ratio
Age- and sex-adjusted Referent 1.00 (0.80-1.24) 1.34 (1.08-1.66) <0.001
Multivariable adjustedd Referent 1.14 (0.92-1.43) 1.36 (1.09-1.69) <0.001
Death from cardiovascular causes
No. of events 298 25 120 153
Rate (95% CI) 0.67 (0.60-0.75) 0.58 (0.39-0.86) 0.57 (0.47-0.68) 0.82 (0.70-0.96)
Hazard ratio
Age- and sex-adjusted Referent 1.02 (0.66-1.57) 1.34 (0.88-2.05) 0.03
Multivariable adjusted Referent 1.28 (0.82-1.99) 1.47 (0.96-2.26) <0.001
Myocardial infarction
No. of events 513 42 202 269
Rate (95% CI) 1.15 (1.06-1.26) 1.19 (0.88-1.62) 0.95 (0.82-1.09) 1.43 (1.27-1.61)
Hazard ratio
Age- and sex-adjusted Referent 0.93 (0.67-1.30) 1.43 (1.04-1.99) <0.001
Multivariable adjusted Referent 1.13 (0.81-1.59) 1.46 (1.05-2.03) 0.003
Stroke
No. of events 664 58 287 319
Rate (95% CI) 1.49 (1.38-1.61) 1.36 (1.05-1.76) 1.37 (1.22-1.54) 1.71 (1.53-1.91)
Hazard ratio
Age- and sex-adjusted Referent 1.05 (0.79-1.39) 1.29 (0.98-1.71) 0.008
Multivariable adjusted Referent 1.16 (0.86-1.54) 1.31 (0.99-1.75) 0.03
All-cause mortality
No. of events 1,982 245 791 946
Rate (95% CI) 4.45 (4.25-4.65) 5.79 (5.11-6.57) 3.94 (3.67-4.22) 4.77 (4.48-5.09)
7
Hazard ratio
Age- and sex-adjusted Referent 0.68 (0.59-0.78) 0.83 (0.72-0.95) 0.95
Multivariable adjusted Referent 0.78 (0.67-0.90) 0.84 (0.73-0.97) 0.30
Abbreviations: BMI, body mass index; BP, blood pressure; CI confidence interval; CKD, chronic kidney disease; JNC, Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; KNHANES, Korea National Health and
Nutrition Examination Surveys; NHIS, National Health Insurance Service; SPRINT, Systolic Blood Pressure Intervention Trial. a BP target used in the SPRINT criteria was defined as systolic BP <120 mm Hg (1) and those used in the JNC 7 hypertension
guidelines were defined as BP <140/90 mm Hg in any ages (18-59 years and ≥60 years) without CKD or diabetes, BP <130/80 mm
Hg in CKD, and BP <130/80 mm Hg in diabetes (3).b Major cardiovascular events included nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Each
component of myocardial infarction and strokes included fatal and nonfatal events.c The event rates were standardized for age and sex. The rates are per 1000 person-years. d For the multivariable-adjusted hazard ratios, data were adjusted for age at baseline, sex, presence or absence of diabetes, presence or
absence of chronic kidney disease, smoking status, presence or absence of hyperlipidemia, body-mass index, use or nonuse of
antihypertensive treatment, use or nonuse of aspirin, use or nonuse of statin therapy, and Charlson comorbidity index.
8
Online Table 4. Standardized Event Rates and Hazard Ratios for Adverse Cardiovascular Events According to Status of BP Control
Based On the SPRINT and 2014 Hypertension Guideline Among Adults with Hypertension in the NHIS Health Examinee Cohort By
the Time-Updated Cox Models, Adjusting Systolic Blood Pressure as a Time-Varying Covariate.
All Adults with
Hypertension
(N=61,222) Status of BP Control Levelsa P for Trend
Variable
Below SPRINT BP
Goal
(N=5,046)
Above SPRINT BP
Goal, but below 2014
Guideline BP Goal
(N=40,118)
Above 2014
Guideline BP Goal
(N=16,058)
Major cardiovascular eventsb
No. of events 890 74 507 309
Rate (95% CI)c 2.07 (1.71-2.43) 2.01 (0.77-3.24) 1.85 (1.43-2.27) 2.68 (1.88-3.48)
Hazard ratio
Age- and sex-adjusted Referent 1.05 (0.82-1.34) 1.53 (1.19-1.97) <0.001
Multivariable adjustedd Referent 1.14 (0.89-1.46) 1.56 (1.20-2.03) <0.001
Death from cardiovascular causes
No. of events 155 12 89 54
Rate (95% CI) 0.36 (0.21-0.51) 0.29 (-0.18-0.77) 0.33 (0.15-0.51) 0.46 (0.13-0.79)
Hazard ratio
Age- and sex-adjusted Referent 1.12 (0.62-2.06) 1.64 (0.88-3.07) 0.03
Multivariable adjusted Referent 1.32 (0.71-2.44) 1.83 (0.96-3.49) 0.03
Myocardial infarction
No. of events 417 31 242 144
Rate (95% CI) 0.97 (0.72-1.22) 0.95 (0.10-1.80) 0.88 (0.59-1.17) 1.22 (0.68-1.76)
Hazard ratio
Age- and sex-adjusted Referent 1.47 (0.79-1.67) 1.62 (1.10-2.39) <0.001
Multivariable adjusted Referent 1.14 (0.89-1.46) 1.59 (1.20-2.03) 0.001
Stroke
No. of events 486 44 271 171
Rate (95% CI) 1.13 (0.86-1.40) 1.09 (0.18-1.99) 0.99 (0.68-1.30) 1.52 (0.91-2.12)
Hazard ratio
Age- and sex-adjusted Referent 0.98 (0.71-1.34) 1.48 (1.06-2.06) <0.001
Multivariable adjusted Referent 1.34 (0.92-1.97) 1.76 (1.17-2.63) 0.001
All-cause mortality
No. of events 1054 126 611 317
10
Rate (95% CI) 2.45 (2.06-2.84) 3.07 (1.55-4.60) 2.23 (1.77-2.69) 2.77 (1.95-3.58)
Hazard ratio
Age- and sex-adjusted Referent 0.72 (0.59-0.87) 0.90 (0.73-1.10) 0.55
Multivariable adjusted Referent 0.85 (0.70-1.04) 1.06 (0.85-1.31) 0.11
Abbreviations: BMI, body mass index; BP, blood pressure; CI confidence interval; CKD, chronic kidney disease; JNC, Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; KNHANES, Korea National Health and
Nutrition Examination Surveys; NHIS, National Health Insurance Service; SPRINT, Systolic Blood Pressure Intervention Trial. a BP target used in the SPRINT criteria was defined as systolic BP <120 mm Hg (1) and those used in the 2014 hypertension guideline
were defined as BP <140/90 mm Hg in ages 18-59 years without CKD or diabetes, BP <150/90 mm Hg in ages ≥60 years without
CKD or diabetes, BP <140/90 mm Hg in CKD, and BP <140/90 mm Hg in diabetes (2).b Major cardiovascular events included nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Each
component of myocardial infarction and strokes included fatal and nonfatal events.c The event rates were standardized for age and sex. The rates are per 1000 person-years. d For the multivariable-adjusted hazard ratios, data were adjusted for age at baseline, sex, presence or absence of diabetes, presence or
absence of chronic kidney disease, smoking status, presence or absence of hyperlipidemia, body-mass index, use or nonuse of
antihypertensive treatment, use or nonuse of aspirin, use or nonuse of statin therapy, Charlson comorbidity index, and systolic BP as
time-varying covariate.
11
Online Table 5. Standardized Event Rates and Hazard Ratios for Adverse Cardiovascular Events According to Status of BP Control
Based On the SPRINT and 2014 Hypertension Guideline Among Adults with Hypertension in the NHIS Health Examinee Cohort
Adopting Alternative Hypertension Definition.a
All Adults with
Hypertension
(N=42,781) Status of BP Control Levelsb P for Trend
Variable
Below SPRINT BP
Goal
(N=4,287)
Above SPRINT BP
Goal, but below 2014
Guideline BP Goal
(N=20,384)
Above 2014
Guideline BP Goal
(N=18,110)
Major cardiovascular eventsc
No. of events 920 89 426 405
Rate (95% CI)d 3.15 (2.95-3.35) 3.05 (2.48-3.76) 2.77 (2.52-3.05) 3.66 (3.32-4.03)
Hazard ratio
Age- and sex-adjusted Referent 0.95 (0.76-1.20) 1.34 (1.07-1.69) <0.001
Multivariable adjustede Referent 0.98 (0.78-1.23) 1.28 (1.02-1.61) <0.001
Death from cardiovascular causes
No. of events 258 25 126 107
Rate (95% CI) 0.88 (0.78-1.00) 0.86 (0.58-1.27) 0.82 (0.69-0.98) 0.97 (0.80-1.17)
Hazard ratio
Age- and sex-adjusted Referent 1.13 (0.74-1.74) 1.24 (0.80-1.92) 0.30
Multivariable adjusted Referent 1.21 (0.77-1.88) 1.37 (0.87-2.16) 0.16
Myocardial infarction
No. of events 402 36 184 182
Rate (95% CI) 1.37 (1.25-1.52) 1.31 (0.94-1.81) 1.21 (1.05-1.40) 1.61 (1.40-1.87)
Hazard ratio
Age- and sex-adjusted Referent 1.01 (0.71-1.45) 1.46 (1.02-2.08) 0.001
Multivariable adjusted Referent 1.05 (0.74-1.51) 1.35 (0.94-1.94) 0.02
Stroke
No. of events 535 54 249 232
Rate (95% CI) 1.83 (1.68-1.99) 1.78 (1.36-2.33) 1.60 (1.42-1.81) 2.14 (1.88-2.43)
Hazard ratio
Age- and sex-adjusted Referent 0.92 (0.69-1.24) 1.29 (0.96-1.74) 0.002
Multivariable adjusted Referent 0.94 (0.70-1.26) 1.26 (0.94-1.70) 0.009
All-cause mortality
No. of events 1,579 201 780 598
13
Rate (95% CI) 5.40 (5.14-5.67) 6.79 (5.92-7.80) 4.93 (4.60-5.29) 5.73 (5.29-6.21)
Hazard ratio
Age- and sex-adjusted Referent 0.72 (0.62-0.84) 0.85 (0.73-1.00) 0.99
Multivariable adjusted Referent 0.78 (0.66-0.91) 0.86 (0.73-1.01) 0.52
Abbreviations: BMI, body mass index; BP, blood pressure; CI confidence interval; CKD, chronic kidney disease; KNHANES, Korea
National Health and Nutrition Examination Surveys; NHIS, National Health Insurance Service; SPRINT, Systolic Blood Pressure
Intervention Trial.a In this analysis, hypertension was alternatively defined as physician-diagnosed, patient-reported BP treatment, or a systolic BP ≥140
mm Hg or a diastolic BP ≥90 mm Hg.b BP target used in the SPRINT criteria was defined as systolic BP <120 mm Hg (1) and those used in the 2014 hypertension guideline
were defined as BP <140/90 mm Hg in ages 18-59 years without CKD or diabetes, BP <150/90 mm Hg in ages ≥60 years without
CKD or diabetes, BP <140/90 mm Hg in CKD, and BP <140/90 mm Hg in diabetes (2).c Major cardiovascular events included nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Each
component of myocardial infarction and strokes included fatal and nonfatal events.d The event rates were standardized for age and sex. The rates are per 1000 person-years. e For the multivariable-adjusted hazard ratios, data were adjusted for age at baseline, sex, presence or absence of diabetes, presence or
absence of chronic kidney disease, smoking status, presence or absence of hyperlipidemia, body-mass index, use or nonuse of
antihypertensive treatment, use or nonuse of aspirin, use or nonuse of statin therapy, and Charlson comorbidity index.
14
Online Figure 1. Participant Inclusion and Exclusion Criteria for the KNHANES Study and the NHIS Health Examinee Cohort
Study.
Online Figure 2. Estimated Percentages of Adults with Hypertension Who Would Meet or Not Meet Blood-Pressure Targets Under
the 2014 Guideline and the SPRINT Criteria, According to Major Subgroups.
Online Figure 3. Ten-Year Predicted Risk of Cardiovascular Events According to Status of
Blood-Pressure Control Under the 2014 Hypertension Guideline and the SPRINT Criteria, as
Measured by the Korean CHD risk score (4).
The mean estimate of the 10-year risk of cardiovascular events on the basis of the Korean CHD
risk score was lowest in adults who met the SPRINT goals (1.46; 95% confidence interval [CI],
1.38 to 1.54), intermediate in those who met the 2014 guideline goals, but not the SPRINT goals
(1.67; 95% CI, 1.63 to 1.71), and highest in those who did not meet the 2014 guideline goals
(2.36; 95% CI, 2.26 to 2.46) (P<0.001).
Online Figure 4. Estimated Percentages of Adults with Hypertension Who Would Meet or Not
Meet Blood-Pressure Targets Under the JNC 7 Guideline and the SPRINT Criteria.
Percentages were weighted on the basis of the KNHANES results. Hypertension was defined as
physician-diagnosed, patient-reported BP treatment, or systolic BP of 130 mm Hg or higher. The
BP target used in the SPRINT criteria was defined as systolic BP <120 mm Hg and those used in
the JNC 7 hypertension guideline were defined as BP <140/90 mm Hg in any ages (18-59 years
and ≥60 years) without CKD or diabetes, BP <130/80 mm Hg in CKD, and BP <130/80 mm Hg
in diabetes.
Online Figure 5. Ten-Year Predicted Risk of Cardiovascular Events According to Status of
Blood-Pressure Control Under the JNC 7 Guideline and the SPRINT Criteria, as Measured by
the Framingham Risk Score.
The mean estimate of the 10-year risk of cardiovascular events on the basis of the Framingham
risk score was lowest in adults who met the SPRINT goals (6.43; 95% confidence interval [CI],
6.10 to 6.76), intermediate in those who met the JNC 7 guideline goals, but not the SPRINT
goals (7.54; 95% CI, 7.30 to 7.78), and highest in those who did not meet the JNC 7 guideline
goals (10.80; 95% CI, 10.55 to 11.05) (P<0.001).
Online Figure 6. Hazard Ratios for Major Cardiovascular Events and Each Component According to Status of Blood-Pressure
Control the JNC 7 Guideline and the SPRINT Criteria.
Major cardiovascular events included nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Each
component of myocardial infarction or stroke included fatal and nonfatal events. Increasing levels of BP control status were classified
according to the SPRINT and the JNC 7 criteria; below SPRINT BP goals vs. above SPRINT goals, but below JNC 7 BP goals vs.
above JNC 7 BP goals. All estimates were adjusted for age, sex, presence or absence of diabetes, presence or absence of CKD,
smoking status, presence or absence of hyperlipidemia, body-mass index, use or nonuse of antihypertensive treatment, use or nonuse
of aspirin, use or nonuse of statin therapy, and Charlson comorbidity index. The bars represent 95% confidence intervals.
Abbreviations: BP, blood pressure; CKD, chronic kidney disease; JNC, Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure; KNHANES, Korea National Health and Nutrition Examination Surveys; SPRINT,
Systolic Blood Pressure Intervention Trial.
21
REFERENCES
1. The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-
Pressure Control. N Engl J Med 2015;373:2103-16.
2. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management
of high blood pressure in adults: report from the panel members appointed to the Eighth
Joint National Committee (JNC 8). JAMA 2014;311:507-20.
3. Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure:
the JNC 7 report. JAMA 2003;289:2560-72.
4. Jee SH, Jang Y, Oh DJ et al. A coronary heart disease prediction model: the Korean
Heart Study. BMJ Open 2014;4:e005025.