Transcript The Metabolic Syndrome

ΜΕΤΑΒΟΛΙΚΟ ΣΥΝΔΡΟΜΟ. ΥΠΕΡΤΑΣΗ
ΚΑΙ ΔΥΣΛΙΠΙΔΑΙΜΙΑ
• Δημήτριος Ρίχτερ, MD, FESC, FAHA
• - Διευθυντής Καρδιολογικής Κλινικής Ευρωκλινικής Αθηνών
• Αντιπρόεδρος ΕΚΟΜΕΝ
• - Γενικός Γραμματέας Ελληνικής Εταιρείας Λιπιδιολογίας.
• - Μέλος ΔΣ ΕΛΙΚΑΡ
NCEP ATP III: The Metabolic Syndrome
Recommends a diagnosis when 3 of these risk factors are present
Risk Factor
Defining Level
Abdominal obesity
(Waist circumference)
Men
Women
>102 cm (>40 in)
>88 cm (>35 in)
150 mg/dL (1.7 mmol/L)
TG
HDL-C
Men
Women
<40 mg/dL (1.0 mmol/L)
<50 mg/dL (1.3 mmol/L)
Blood pressure
130/85 mmHg
Fasting glucose
110 mg/dL (6.0 mmol/L)
Adapted from NCEP, Adult Treatment Panel III, 2001. JAMA 2001:285;2486–2497.
PREVALENCE OF METS IN GREECE
• Mets-Greece study (Athyros et al). 4056 adults.
Prevalence 22.8%. Similar men and women. Increasing with age
( 4,7% 18-29y, 44,2% >60y).
62% 3 components, 28% 4, 10% all 5.
74th EAS Congress, Seville, 17-20 April 2004
ATTICA study (Panagiotakos et al). 2282 adults.
Prevalence 19,8%. Men 25,2%, women 14,6%.
Prevalence increased with age.
Am Heart J 2004; 147: 106-12.
The presence of the Metabolic Syndrome is
associated with increased CHD, CVD and
total mortality
Unadjusted Kaplan-Meier hazard curves for men with and without the Metabolic Syndrome
based on factor analysis. Median follow-up was 11.6 (9.1-13.7) years. Relative risks were
determined by age-adjusted Cox proportional hazards regression analysis.
Lakka HM et al, J Am Med Assoc 2002;288:2709-2716
Association of MI* With the Metabolic
Syndrome and Individual Components
©2004 PPS®
Odds Ratio
95% CI
P Value
2.01
1.53-2.64
<0.0001
Abdominal obesity
1.15
0.86-1.54
0.3475
High triglycerides
1.51
1.04-2.20
0.0311
Low HDL-C
1.41
1.03-1.95
0.0353
Hypertension
1.42
0.94-2.15
0.0947
Insulin resistance†
1.25
0.92-1.71
0.1461
Metabolic syndrome
Syndrome components
*Self-reported.
†Fasting plasma glucose 110 mg/dL.
Ninomiya JK et al. Circulation. 2004;109:42-46.
Association of Stroke* With the Metabolic
Syndrome and Individual Components
©2004 PPS®
Odds Ratio
95% CI
P Value
2.16
1.48-3.16
0.0002
Abdominal obesity
0.97
0.58-1.64
0.9154
High triglycerides
1.87
1.22-2.87
0.0052
Low HDL-C
1.18
0.73-1.90
0.5012
Hypertension
1.56
0.94-2.59
0.0827
Insulin resistance†
1.36
0.93-1.98
0.1119
Metabolic syndrome
Syndrome components
*Self-reported.
†Fasting plasma glucose 110 mg/dL.
Ninomiya JK et al. Circulation. 2004;109:42-46.
Major causes of death in USA
1990 and 2000
1990
2000
100
Percentage
80
60
40
20
19
18,1
14
16,6
0
Smoking
Diet and sedentarity
Mokdad AH et al. JAMA 2004
Risk of AMI associated with risk factors
in the overall population
Risk factor
% Cont % Cases OR (99% IC) adj OR (99% IC) adj
for all
age, sex, smoking
ApoB/ApoA-1 (5 v 1)
20.0
33.5
3.87 (3.39, 4.42) 3.25 (2.81, 3.76)
Smoking
26.8
45.2
2.95 (2.72, 3.20) 2.87 (2.58, 3.19)
Diabetes
7.5
18.4
3.08 (2.77, 3.42) 2.37 (2.07, 2.71)
Hypertension
21.9
39.0
2.48 (2.30, 2.68) 1.91 (1.74, 2.10)
Abd Obesity (3 v 1)
33.3
46.3
2.22 (2.03, 2.42) 1.62 (1.45, 1.80)
-
-
2.51 (2.15, 2.93) 2.67 (2.21, 3.22)
Veg et fruits DIE
42.4
35.8
0.70 (0.64, 0.77) 0.70 (0.62, 0.79)
Exercise
19.3
14.3
0.72 (0.65, 0.79) 0.86 (0.76, 0.97)
Alcohol intake
24.5
24.0
0.79 (0.73, 0.86) 0.91 (0.82, 1.02)
Psychosocial
Yusuf S et al, Lancet 2004
Declining HDL-C in the Population
Women


>12,000 respondents to a
biennial population survey
in the Pawtucket Heart
Health Program
Between 1981 and 1993,
0.08 mmol/L (3.1 mg/dL)
decline
Adjusted for other risk
factor changes
HDL-C (mmol/L)

1.5
Men
1.3
Nonsmokers
1.4
Nonsmokers
1.2
1.3
1.1
1.2
1.0
1.1
Smokers
0.0
1.5
0.0
Alcohol
Smokers
1.3
1.4
Alcohol
1.2
1.3
1.1
1.2
1.1
1.0
No Alcohol
0.0
0.0
BMI <22.9
1.5
1.4
No Alcohol
BMI <24.5
1.3
1.2
1.3
1.1
1.2
1.0
1.1
0.0
0.0
BMI 27.6
'81-82
'85-86
'83-84
Reprinted from Ann Epidemiol, Vol. 8, Derby CA et al., 84-91, copyright 1998, with
permission from Elsevier.
'89-90
'87-89
'92-93
BMI 27.9
'81-82
'85-86
'83-84
'89-90
'87-89
'92-93
Treatment of obesity
Modest weight loss can be effective
 ~250-500 kcal/day restriction
 energy expenditure as tolerated
Monitor blood pressure with anorectic drugs
Treat CHD, LVH and RVH risk factors
aggressively
lipids, blood pressure, diabetes, hypertension
obstructive sleep apnea and respiratory
problems
Poirier et al, Circulation 2006
Finnish Diabetes Prevention Study: Treating
the IGT* Patient With Lifestyle Changes

Study Design
– 522 middle-aged, overweight† subjects
– 172 men, 350 women with IGT
– BMI 31 kg/m2
– mean age: 55 years
– mean duration: 3.2 years
– intervention group: individualized counseling
• reducing weight, total intake of fat and saturated fat
• increasing intake of fiber, physical activity
*Plasma glucose concentration of 140 to 200 mg/dL.
†BMI 25 kg/m2.
IGT=impaired glucose tolerance; BMI=body mass index.
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
Finnish Diabetes Prevention Study:
Reduction in Risk for Diabetes*
23%
25
(n=257)
20
Diabetes
(%)
15
11%
10
(n=265)
5
0
*P<0.001; 4-year results
Intervention
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
Control
Bariatric surgery and mortality
• Prospective study
• SOS study
• N=4047 patients
• 10.9 yrs follow-up
• Information: 99.9%
Sjostrom L et al, NEJM 2007
SOS: Mortality reduction with weight-loss surgery
14
12
Deaths:
Control: 129 (6.3%)
Surgery: 101 (5.0%)
Control
10
Cumulative
mortality
(%)
Unadjusted HR 0.76
(0.59-0.99), P = 0.04
8
6
Adjusted HR 0.71*
(0.54-0.92), P = 0.01
Surgery
4
2
0
0
2
*Adjusted for age, sex, risk factors
4
6
8
10
Years
12
14
16
Sjöström L et al. N Engl J Med. 2007;357:741-52.
SOS: Causes of death
Surgery
(n)
Controls
(n)
Cardiovascular condition
43
53
Cardiac
Myocardial infarction
Heart failure
Sudden death
13
2
20
25
5
14
Stroke
6
6
Other
2
3
Noncardiovascular condition
58
76
Cancer/meningioma
29/0
47/1
Infection
12
3
Thromboembolic disease
5
7
Other
12
18
Total mortality
101
129
Sjöström L et al. N Engl J Med. 2007;357:741-52.
2007 Guidelines
for the Management of
Arterial Hypertension
European Society of Hypertension
European Society of Cardiology
Journal of Hypertension 2007;25:1105-1187
Initiation of antihypertensive treatment
High normal
SBP 130-139 or
DBP 85-89
Grade 1 HT
SBP 140-159 or
DBP 90-99
Grade 2 HT
SBP 160-179 or
DBP 100-109
Grade 3 HT
SBP ≥180 or
DBP ≥110
No BP
intervention
Lifestyle changes
for several
months then drug
treatment if BP
uncontrolled
Lifestyle changes
for several weeks
then drug
treatment if BP
uncontrolled
Lifestyle
changes +
immediate
drug
treatment
Lifestyle changes
Lifestyle changes
Lifestyle changes
for several weeks
then drug
treatment if BP
uncontrolled
Lifestyle changes
for several weeks
then drug
treatment if BP
uncontrolled
Lifestyle
changes +
immediate
drug
treatment
3 or more risk
factors, MS,
OD or diabetes
Lifestyle changes
Lifestyle changes
and consider
drug treatment
Lifestyle changes
+ drug treatment
Diabetes
Lifestyle changes
Lifestyle changes
+ drug treatment
Lifestyle
changes +
immediate
drug
treatment
Lifestyle changes
+ immediate drug
treatment
Lifestyle
changes +
immediate
drug
treatment
Other risk
factors, OD or
disease
No other risk
factors
1-2 risk factors
Established CV
or renal
disease
Normal
SBP 120-129 or
DBP 80-84
No BP
intervention
Lifestyle changes
+ immediate drug
treatment
Lifestyle changes
+ immediate
drug treatment
Lifestyle changes
+ drug treatment
Lifestyle changes
+ immediate drug
treatment
The Metabolic Syndrome
• Subjects with the metabolic syndrome also have a higher
prevalence of microalbuminuria, left ventricular hypertrophy
and arterial stiffness than those without the metabolic
syndrome. Their cardiovascular risk is high and the chance of
developing diabetes markedly increased
• In patients with a metabolic syndrome diagnostic procedures
should include a more in-depth assessment of subclinical
organ damage. Measuring ambulatory and home BP is also
desirable
The Metabolic Syndrome
• In all individuals with metabolic syndrome individuals intense
lifestyle measures should be adopted. When there is
hypertension drug treatment should start with a drug unlikely
to facilitate onset to diabetes. Therefore, a blocker of the
renin-angiotensin system should be used followed, if needed,
by the addition of a calcium antagonist or a low-dose thiazide
diuretic. It appears desirable to bring BP to the normal range
• Lack of evidence from specific clinical trials prevents firm
recommendations on use of antihypertensive drugs in all
metabolic syndrome subjects with a high normal BP. There is
some evidence that blocking the renin-angiotensin system may
also delay incident hypertension
Hypertension Guidelines:
ESH/ESC 2013
Definitions and classification of office
blood pressure levels (mmHg)
Category
Systolic
Diastolic
Optimal
< 120
And
< 80
Normal
120-129
And/or
80-84
High normal
130-139
And/or
85-89
Grade 1
hypertension
140-159
And/or
90-99
Grade 2
hypertension
160-179
And/or
100-109
Grade 3
hypertension
> = 180
And/or
> = 110
Isolated systolic
hypertension
>= 140
and
< 90
BP Goals
• all be treated to <140/90 mm Hg
• Except : diabetes (<85 mm Hg diastolic)
• In patients near 80 years age, the systolic bloodpressure target should be 140 to 150 mm Hg, but
physicians can go lower than 140 mm Hg if the
patient is fit and healthy-mentally & physically
Life style changes
Salt
• A reduction to 5 g per day can decrease systolic blood pressure
about 1 to 2 mm Hg in normotensive individuals and 4 to 5
mm Hg in hypertensive patients, he said.
Wt loss
• Losing about 5 kg can reduce systolic blood pressure by as
much as 4 mm Hg, aerobic endurance training
• can reduce systolic blood pressure 7 mm Hg
When to start drug Rx
Consider BP level and correlate with overall risk:
• cardiovascular risk factors
• overt cardiovascular disease
• asymptomatic organ damage
• diabetes
• chronic kidney disease.
Asymptomatic Target Organ Damage
(TOD)
√ Pulse pressure ( in the elderly) >= 60 mmHg
Electrocardiograhic LVH( Sokolow-Lyon index > 3.5 mV; RaVL > 1.` mV;
Cornell voltage duration product> 244 mV* ms), or
Echocardiographic LVH [ LVM index: men > 115 g/m2; women > 95 g/m2
(BSA)]a
Carotid wall thickening (IMT > 0.9 mm) or plaque
Carotid- femoral PWV > 10 m/s
√ Ankle- brachial index < 0.9
CKD with Egfr 30-60 ml/min/1.73 m2 (BSA)
Microalbuminuria (30-300 mg/24 h), or albumin- creatinine ratio(30-300 mg/g;
3.4-34 mg/mmol) (preferentially on morning spot urine)
Combination Rx
• For patients at high risk for cardiovascular events or those with
a markedly high baseline blood pressure
• In those at low or moderate risk for cardiovascular events or
with mildly elevated blood pressure, a single starting agent is
preferred.
• For a high-risk individual, you can't play around with one drug
after another, trying to control blood pressure
Drugs to be preferred in specific conditions
Compelling and possible contra-indications
to the use of antihypertensive drugs
Patients with CHD event (%)
Effects of lipid-lowering therapy on
CHD events in statin trials
Secondary
Prevention
4S-P
25
Primary
Prevention
20
4S-S
Simvastatin
LIPID-P
15
CARE-P
HPS-P
LIPID-S
10
CARE-S
5
Pravastatin
Lovastatin
WOSCOPS-P
Atorvastatin
WOSCOPS-S
HPS-S
ASCOT-P*
ASCOT-S*
S=statin treated
P=placebo treated
AFCAPS-P
AFCAPS-S
*Extrapolated to 5 years
0
90
110
130
150
170
LDL-C (mg/dL)
Modified from Kastelein JJP. Atherosclerosis. 1999;143(Suppl 1): S17-S21.
190
210
Metabolic Syndrome Subgroup
TNT Study Design: Post-Hoc Analysis of
Patients With Metabolic Syndrome
Metabolic syndrome was based on the updated NCEP ATP III definition,1
and was defined as 3 of the following prior to open-label run-in:
 Waist circumference: Men 40 inches (102 cm); Women 35 inches (88 cm)*
Triglycerides 150 mg/dL (1.7 mmol/L)
 HDL-C: Men <40 mg/dL (<1.0 mmol/L); Women <50 mg/dL (<1.3 mmol/L)
 Blood pressure 130/85 mm Hg
 Fasting glucose 100 mg/dL (5.6 mmol/L)
Screening
and wash-out
Double-blind period
n=5584
Open-label
run-in
Baseline
Atorvastatin
10 mg
1-8 weeks
8 weeks
*BMI 28 substituted for waist circumference
n=2820
Atorvastatin 10 mg
LDL-C target: 100 mg/dL (2.6 mmol/L)
n=2764
Atorvastatin 80 mg
LDL-C target: 75 mg/dL (1.9 mmol/L)
Median follow-up = 4.9 years
1Grundy
SM et al. Circulation. 2005;112:2735-2752.
Metabolic Syndrome Subgroup
Time to First Major Cardiovascular Event
in Patients with Metabolic Syndrome (MetS)
Cumulative incidence of major
cardiovascular events*
20
18
All metabolic syndrome
Atorvastatin 10 mg (n=2820)
Atorvastatin 80 mg (n=2764)
16
HR = 0.71 (95% CI: 0.61, 0.84) P<.0001
14
Metabolic syndrome, no diabetes
Atorvastatin 10 mg (n=2191)
Atorvastatin 80 mg (n=2162)
12
HR = 0.70 (95% CI: 0.57, 0.84) P=.0002
10
8
6
4
2
0
0
1
2
*Coronary heart disease death, nonfatal non–procedurerelated myocardial infarction, resuscitated cardiac arrest,
fatal or nonfatal stroke
3
4
5
6
Time (years)
Deedwania P et al. Lancet. 2006;368:919-928.
Metabolic Syndrome Subgroup
First Major Cardiovascular Event in Patients
With Metabolic Syndrome: Summary
End point
No. of patients (%)
Atorvastatin 10 mg
(n=2820)
Atorvastatin 80 mg
(n=2764)
367 (13.0)
262 (9.5)
CHD death
66 (2.3)
46 (1.7)
Nonfatal non–PR MI
201 (7.1)
139 (5.0)
Resuscitated cardiac arrest
6 (0.2)
10 (0.4)
Fatal/Nonfatal stroke
94 (3.3)
67 (2.4)
Major cardiovascular event*
*HR = 0.71 (95% CI: 0.61, 0.84)
P<.0001
Data on file, Pfizer Inc, New York, NY.
Metabolic Syndrome Subgroup
Secondary Event Rates in Patients With
Metabolic Syndrome (MetS) and Overall
Event rate (MetS)
10 mg
80 mg
Any CV event
MetS 30.9%
37.6%
Event rate (overall) 10 mg
80 mg
33.5%
28.1%
8.3%
6.7%
26.5%
21.6%
5.0%
3.9%
3.3%
2.4%
5.6%
5.5%
5.6%
5.7%
Any CV event
Major coronary
MetS 7.3%
9.9%
Major coronary event
Any coronary
MetS 23.3%
29.8%
Any coronary event
Cerebrovascular
MetS 4.5%
6.0%
Cerebrovascular event
CHF with hosp.
MetS 3.1%
4.2%
CHF with hospitalization
PAD
MetS 6.3%
6.5%
PAD
All-cause mortality
MetS 6.2%
6.3%
All-cause mortality
0.4
0.6
0.8
1.0
1.2
1.4
Atorvastatin 80 mgHazard
betterratio (95% CI) Atorvastatin 10 mg better
Deedwania P et al. Lancet. 2006;368:919-928.
Treating HDL:
Nonpharmacologic Methods
7
 Exercise overrated
P=0.015
 HDL only with intense,
frequent exercise
 Alcohol
 Raises TG
 Affects CETP activity
 Modest HDL changes
 Smoking cessation
Changes in HDL-C
Concentration (mg/dL)
 HDL only when TG high
Frequent, intense
exercise
4
Infrequent
exercise
1
0
 Weight loss
Control
Moderate
Intense
-2
Couillard C et al. Arterioscler Thromb Vasc Biol 2001;21:1226-1232. | Kraus WE et
al. N Engl J Med 2002;347:1483-1492. Copyright 2002 Massachusetts Medical
Society. All rights reserved.
Slide Source
LipidsOnline
www.lipidsonline.org
HDL-C Response to Exercise
Lipids and Exercise
Duration of exercise effect on lipids
 TG increase delays for several hours after exercise and this effect
can persist for 24-48 hours or several days when exercise is
prolonged and intense.
 Usually HDL begins to rise after >10 weeks of exercise
 Single exercise sessions reduce postprandial hyperlipidemia but
have no other effect on lipids.
 After exercise cessation lipids return on original values
 The longer the exercise program lasted the longer the favorable
lipid profile remains after exercise cessation.
Smoking Cessation Increases HDL-C Level
• In study by Moffatt, smokers had HDL-C levels 15–20%
lower than nonsmokers (P < 0.05).1
– PROCAM showed less of an effect of smoking on
HDL-C (7% lower than nonsmokers).2
• HDL-C levels returned to normal within 30–60 days after
smoking cessation.1
• In eight women who smoked > 1 packs per
day for 5 years, HDL-C levels increased from
51 to 64 mg/dL after quitting for 60 days.1
1. Moffatt RJ. Atherosclerosis 1988;74:85–89
2. Cullen P et al. Eur Heart J 1998;19:1632–1641
Weight and HDL-C
• Inverse correlation between body weight and
HDL-C is consistently observed in both men and
women.
• For every 3 kg of weight loss, HDL-C levels
increase 1 mg/dL.
Dattilo AM, Kris-Etherton PM. Am J Clin Nutr 1992;56:320–328
Caloric Restriction Acutely
Lowers HDL-C Level
• Trials of very-low-calorie diets show that HDL-C levels
decrease by 2–12 mg/dL during acute caloric restriction.
• After 12 wks, HDL-C returned to pretreatment range, and
this trend was still apparent after 1 year.
• Therefore, benefits of weight-loss programs should not be
assessed during acute caloric restriction.
Rössner S et al. Atherosclerosis 1987;64:125–130
Alcohol Increases HDL-C Level
• Alcohol increases HDL-C level in a dose-dependent manner.
• Half bottle of wine per day (39 g alcohol) for 6 weeks significantly
increased mean HDL-C level by 7 mg/dL in
12 healthy subjects.1
– Wine intake did not significantly affect Total-C,
Total-TG, or LDL-C.1
• One beer per day (13.5 g alcohol) for 6 weeks significantly increased
mean HDL-C level by 2 mg/dL in 20 healthy subjects.2
– Beer intake did not significantly affect LDL-C,
VLDL-C, TG, or apolipoproteins.
1. Thornton J et al. Lancet 1983;ii:819–822
2. McConnell MV et al. Am J Cardiol 1997;80:1226–1228
HDL-C Response to Pharmacological Intervention
ACCORD Study Design
• Overall ACCORD Glycemia Trial: 10,251 participants
• Lipid Trial: 5,518 in Lipid Trial
• 2765 randomized to fenofibrate
• 2753 randomized to placebo
• Primary Outcome: First occurrence of a major cardiovascular event
(nonfatal MI, nonfatal stroke, cardiovascular death)
• 87% power to detect a 20% reduction in event rate, assuming
placebo rate of 2.4%/yr and 5.6 yrs follow-up in participants
without events.
ACCORD Lipid Trial Eligibility
• Stable Type 2 Diabetes >3 months
• HbA1c 7.5% to 11%
• High risk of CVD events = clinical or subclinical disease or
2+ risk factors
• Age (limited to <80 years after Vanguard)
•
•
≥ 40 yrs with history of clinical CVD (secondary prevention)
≥ 55 yrs otherwise
• Lipids
•
•
•
60 < LDL-C < 180 mg/dl
HDL-C < 55 mg/dl for women/Blacks; < 50 mg/dl otherwise
Triglycerides < 750 mg/dl if on no therapy; < 400 mg/dl otherwise
• No contraindication to either fenofibrate or simvastatin
Characteristic
Mean or %
Characteristic
Mean or %
Age (yrs)
62
Total Cholesterol (mg/dl)
175
Women %
31
LDL-C (mg/dl)
101
HDL-C (mg/dl)
38
162
Race / Ethnicity
White %
68
Triglyceride (mg/dl)*
Black %
15
Blood pressure (mm Hg)
134/74
Hispanic %
7
Serum creatinine (mg/dl)
0.9
Secondary prevent %
37
Current smoking %
15
DM duration (yrs)*
9
On a statin %
60
A1c (%) *
8.3
On another LLA %
8
BMI (kg/m2)
32
On Insulin %
33
*
Median values
Mean LDL-C
200
120
190
110
180
100
Feno
170
Placebo
mg/dl
mg/dl
Mean Total Cholesterol
160
80
150
70
140
0
N = 5483
1
5180
2
3
4
5
6
7
4988
4783
5250
3377
1668
491
Feno
90
Placebo
60
Years PostRandomization
0
1
N = 5483
5180
3
4
5
6
4988
4783
5250
3377
1668
7
Years PostRandomization
491
Median Triglycerides
42
170
41
160
150
40
Feno
Placebo
39
mg/dl
mg/dl
Mean HDL-C
2
Feno
140
Placebo
130
38
120
37
0
N = 5483
1
5180
2
3
4
5
6
4988
4783
5250
3377
1668
7
491
Years PostRandomization
110
0
N = 5432
1
2
3
4
5180
4988
4783
5250
5
3377
6
7
1668
491
Years PostRandomization
Primary Outcome
Fenofibrate
(N=2765)
Rate
N of
(%/yr)
Events
Primary Outcome:
Major Fatal or Nonfatal
Cardiovascular Event
291
2.24
Placebo
(N=2753)
Rate
N of
(%/yr)
Events
310
2.41
HR (95% CI)
P Value
0.92
0.32
(0.79 - 1.08)
Prespecified Secondary Outcomes
Fenofibrate
(N=2765)
N of
Rate
Events
(%/yr)
Placebo
(N=2753)
N of
Rate
Events
(%/yr)
HR (95% CI)
P Value
Outcome
Primary + Revasc +
hospitalized CHF
641
5.35
667
5.64
0.94 (0.85-1.05)
0.30
Major Coronary Event
332
2.58
353
2.79
0.92 (0.79-1.07)
0.26
Nonfatal MI
173
1.32
186
1.44
0.91 (0.74 - 1.12)
0.39
Total Stroke
51
0.38
48
0.36
1.05 (0.71 - 1.56)
0.80
Nonfatal Stroke
47
0.35
40
0.30
1.17 (0.76 - 1.78)
0.48
Total Mortality
203
1.47
221
1.61
0.91 (0.75 - 1.10)
0.33
Cardiovascular Death
99
0.72
114
0.83
0.86 (0.66 - 1.12)
0.26
Fatal/Nonfatal CHF
120
0.90
143
1.09
0.82 (0.65 - 1.05)
0.10