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SHEP - 14 YEAR FOLLOW-UP
50
40
CV death (%)
40
30
PLACEBO
20
15 13 13
10
ACTIVE
10
45
0
2020/9/23
* = p< 0.05 vs no diabetes
CONCLUSIONS FROM SHEP +
• Chlorthalidone Rx of hypertension improves longterm outcomes.
Systolic BP and CV Death in MRFIT
CV mortality rate per 10,000 person-years
250 225 200 175 150 125 100
75 50 25
0
Nondiabetic (n=342,815) Diabetic (n=5,163)
• NOD has consequences
– Non-CVD in short term – CVD long term
2020/9/23
CVD Consequences
• Short and Long term • Antihypertensive Drug Related
2020/9/23
ALLHAT Incidence of Coronary heart disease by treatment group according to baseline diabetes
20
15 13 13 10
10
Microv4asc5ular
endpoints
110120 130140150 160170 Mean SBP (mmHg)
0 5 6 7 8 9 10 11 Updated mean HbA1c concentration (%
Adler AI, et al. BMJ. 2000;321:412-419. Stratton IM, et al. BMJ. 2000;321:405-412. . 2020/9/23
2020/9/23
Non-CVD Consequences of NOD
• Impaired BP control • Behavioral and Psychological • Microvascular consequences (?) • Medical care demands • Treatment changes
2020/9/23
Prevalence of diabetes among Chinese adults aged 35–64 years in the 1994 Chinese
National Survey (10) and 2000–2001 InterASIA Study
50
40
40
30
20
50
40
40
30
20
15
13 13
10
10
4
5
0
Aksnes, T. A. et al. Hypertension 2007;50 2020/9/23
ALLHAT
Diabetes Incidence - 4 Years
(follow-up FBS 126 mg/dL for those <126 mg/dL at baseline)
2020/9/23
HOT
Major CV Event Rate In HOT
Non-Diabetic subjects
Diabetic population
No
p = 0.005 51% risk reduction
Image
85.2 83.2 81.1 DBP achieved
< 90 < 85 < 80 < 90 < 85 < 80
130-139
>140
Age-adjusted incidence rates (A) and HRs (B) of NOD according to blood pressure category, stratified by baseline body mass index
. Conen2, 0D2.0e/9t/2a3l. Eur Heart J 2007 28:2937-2943
cause mortality, combined CHD, stroke, HF, all CVD, and ESRD
50
40
40
30
20
15 13 13 10
10
45
0
Wh.elton2,0P2.0K/9. /e2t3al. Arch Intern Med 2005;165:1401-1409.
50
40
40
30
20
15
13 13
10
10
4
5
0
Barzilay2, 0J2. 0I./9e/t2a3l ALLHAT. Arch Intern Med 2006;166:2191-2201.
50 40
40
30
20 10
15
13
13
10
4
5
0
Effect of ACEIs and ARBs on CVD Mortality
10
45
0
Dream. 2N0E2J0M/9/;23355:1551-1562,2006
Ramipril v. Placebo CVD & non-CVD Outcomes
Dream. NEJM;355:1551-1562,2006
2020/9/23
ALLHAT: RR (and 6-year rates per 100 for nondiuretic compared with diuretic for diabetes mellitus (A), impaired fasing glucose level (B), and normoglycemia (C) at baseline, for CHD, all-
* *
* p<.05 compared to chlorthalidone
2020/9/23
JAMA 2002;288:2981-2997
Ramipril v. Placebo in high risk patients with IGT at baseline
50
40
40
30
20
15 13 13 10
Adjusted incidence per 1000 person-years (%)
Adjusted incidence per 1000 person-years (%)
Myocardial infarction
50
40
40
30
Myocardial infarction
Microvascular endpoints
THE ISSUES
• CONSEQUENCES OF NOD
– CVD AND non-CVD
• HOW DO ANTIHYPERTENSIVE DRUGS EFFECT INCIDENCE OF NOD AND CVD ONSEQUENCES?
• HOW SHOULD NOD EFFECT MANAGEMENT FOR CVD PROTECTION?
Gilles20p20i/e9/2,3 et al. Diabetes Care 28:2261-2266, 2005
Age-gender–adjusted in treatment CVD and non-CVD by baseline FBG among
hypertensive patients.
NHANES 18 year Follow-up NOD in US Women by Baseline BP
50
40
40
30
20
15
13
13
10
10
4
5
0
mmHg <120 120-129
2020/9/23 Conen, D. et al. Eur Heart J 2007 28:2937-2943
Annual Incidence of Diabetes in Hypertensive Patients
• SHEP untreated controls = 2.7% • SHEP treated = 3.9%
Lanc2e0t2.02/90/0263, 368;1673-1679, Am J Cardiol. 2005;95:29,Hypertension.2007;50:467, JAMA 2002;288:2981-2997
Source # studies #subjects OR (95% CI)
All
11 109,052 0.96(0.91-1.01)
ACEI ARB
6百度文库
74,626 0.93(0.81-1.06)
5
34,426 0.93 (0.81-1.06)
HTN
7
86,414 0.99 (0.93--
1.06)
15 13 13
10
10
4
5
0
G2u020e/9/t23al Diabetologia. 2003;46:1190.
Percent of deaths
65% of Mortality in people with Diabetes is CVD
50
40
40
30
20
15
13
13
10
10
4
5
0
Geiss LS, et al. In: Diabetes in America. Nat2i0o2n0/a9/l23Institutes of Health;1995.
2020/9/23
Reduction in major CVD among 6,000 DM in HPS associated with 38/89 LDL/CHOL by Statin
2020/9/23
Incidence of MI and Microvascular Endpoints by Mean SBP and HbA1c in UKPDS
<120 120-139140-159160-179180-199 200 Systolic BP (mmHg)
BP= blood pressure CV=cardiovascular MRFIT=Multiple Risk Factor Intervention Trial Sta2m02l0e/9r/2J3, et al. Diabetes Care. 1993;16:434-444.
• The diabetes related to chlorthalidone therapy has better prognosis than diabetes at baseline.
• The benefit of chlorthalidone-based therapy on long-term total and CV mortality is most pronounced in hypertensive patients with diabetes.
MI=myocardial infarction SBP=systolic blood pressure
UNCERTAINTY CONTINUES ACCORD AND ADVANCE
• ACCORD - Mortality greater with HbAlc <6.4 v. 7.0-7.9%
• ADVANCE - No evidence of mortality with HbAlc 6.4 v. 7,5%
mellitus, impaired fasting glucose level, or normoglycemia
Whe.lton,2P0.2K0./9e/t2a3l. Arch Intern Med 2005;165:1401-1409.
HR’s of a 10-mg/dL (0.56-mm) FBG at 2 years for subsequent CVD and Renal Disease
No Image
Al2d0e2r0m/9/a2n3 , Hypertension. 1999;33:1130-1134
Myocardial infarction (fatal and nonfatal) in hypertensive patients according to DM status
Goal Diastolic mmHg
Lan2c0e2t0/19/9293 8;351:1755
CONCLUSIONS
• DM serious whenever it occurs
– More common in hypertensive Rx
– Particularly with diuretics
