Towards optimized BP control in China Jiguang WANG, MD, PhD The Shanghai Institute of Hypertension...
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Towards optimized BP control in China Jiguang WANG, MD, PhD The Shanghai Institute of Hypertension [email protected]
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Transcript of Towards optimized BP control in China Jiguang WANG, MD, PhD The Shanghai Institute of Hypertension...
Towards optimized BP
control in China
Jiguang WANG, MD, PhDThe Shanghai Institute of Hypertension
High prevalence and low control rates
High sodium and low potassium intakes
High night-time BP and low dipping
High stroke and increasing coronary event rates
High profile of CCBs
Prevalence of hypertension in China
Awareness, treatment and control rates of hypertension in China
Prevalence Number of patients
Awareness Treated Controlled
1991 (>15 y)
11.3 ％ 94 million 26.6 ％ 45.5% (12.1 ％ )
23.1% (2.8 ％ )
2002 (18 y ）
18.8 ％ 160 million 30.2 ％ 81.8% (24.7 ％ )
25.0% (6.1 ％ )
2002 (60 y ）
49.1 ％ ~70 million 37.6 ％ 96.3% (36.2 ％ )
24.1% (7.6 ％ )
Chin J Hypertens 1995;3(suppl):14 -18; Li Liming, et al. ChinJ E pidemiol 2005;26:,478-484.
高血压控制率：中国 vs 美国
Li Liming, et al. ChinJ E pidemiol 2005;26:,478-484. Chobanian AV. N Engl J Med 2009;361:878-87.
High prevalence and low control rates
High sodium and low potassium intakes
High night-time BP and low dipping
High stroke and increasing coronary event rates
High profile of CCBs
Urinary and PRA measurements in northern Chinese Urinary and PRA measurements in northern Chinese
Parents Offspring Fathers Mothers Sons
Daughters (n=110) (n=116) (n=130) (n=123)
Urinary volume (L/day) 1.70 1.63 1.46 1.37
Urinary creatinine (mmol/day) 8.7 6.4 8.6 6.9
Urinary Na+ (mmol/day) 247 218 231 207
Urinary K+ (mmol/day) 39 39 37 37
Urinary Na+/K+ ratio 6.63 6.07 6.56 5.96
PRA (ng/L/sec) 0.36 0.45 0.72 0.71 Wang JG, et al. J Hypertens 2004; 22: 937-944.
Men Women (n=204) (n=223)
24-h Urinary excretion
Volume, L 1.14 ± 0.54 0.98 ± 0.44*
Creatinine, mmol 7.50 ± 2.89 6.32 ± 2.16*
Na+, mmol 147.9 ± 75.6 158.7 ± 71.5
K+, mmol 24.7 ± 11.8 26.8 ± 12.9
Na+/K+ ratio 6.37 ± 2.55 6.43 ± 2.56 * Plasma renin activity, ng/ml/h 1.44 (1.24-1.68) 1.13 (0.95-1.34)*
*P<0.05
Urinary and PRA measurements in southern Chinese
Li Y, et al. Kidney Int 2006; 69: 1153-1158.
Owner
As expected, men had higher urinary volume, creatinine and plasma renin activity. I would like to draw your attention to sodium patassium ratio, about two times higher than in western populations, mainly because of the very low potassium intake.
INTERMAP: Urinary Na+/K+ excretion
Zhou BF et al. J Hum Hypertens 2003;17:623–630.
Japan China UK USA
Men
Urinary Na+ (mmol/day) 211 245 161 183
Urinary K+ (mmol/day) 49.2 38.6 74.7 64.4
Urinary Na+/K+ (mmol/mmol) 4.5 6.8 2.3 3.1
Women
Urinary Na+ (mmol/day) 186 210 127 142
Urinary K+ (mmol/day) 48.5 37.9 61.0 50.8
Urinary Na+/K+ (mmol/mmol) 4.1 6.0 2.2 3.1
HYVET: Serum concentrations of cholesterol, sodium and potassium
Liu LS et al. Chin Med J 2008; 121:1509-1512.
Men Women
Characteristic (mmol/L)China
Other countries
China Other countries
Total cholesterol 4.69±1.0 5.45±1.1 5.02±1.1 5.60±1.1
HDL cholesterol 1.37±0.36 1.29±0.39 1.43±0.36 1.33±0.43
Sodium 140±4.1 142±4.1 140±4.1 142±4.3
Potassium 4.25±0.47 4.42±0.40 4.26±0.49 4.38±0.40
SHEP: New-onset diabetes mellitus
Shafi T et al. Hypertension 2008;52:1022-9.
45% per 0.5 mmol/L in K+
High prevalence and low control rates
High sodium and low potassium intakes
High night-time BP and low dipping
High stroke and increasing coronary event rates
High profile of CCBs
Ambulatory SBP/DBP in normotensive subjects across populationsAmbulatory SBP/DBP in normotensive subjects across populations
BPS EPOGH AIB PAMELA Ohasama Taiwan Jingning
Mercury 118 117 115 115 121 119 116
/74 /75 /73 /72 /70 /74 /74
Daytime 121 122 122 120 121 118 119
/75 /75 /77 /77 /72 /75 /78
Night-time 104 105 104 105 106 114 105 /60 /61 /59 /63 /61 /71 /66
Li Y et al. Blood Press Monit 2005; 125.
15
10
5
0
20
Nocturnal BP fall across populationsNocturnal BP fall across populations
Nocturnal BP fall
(mm Hg)
BPS EPOGH AIB PAMELA Ohasama Taiwan Jingning
Li Y et al. Blood Press Monit 2005; 125.
SBPDBP17
15
17
14
18 18
1514
15
11
4 4
14
12
Isolated nocturnal hypertension
150
140
130
120
110
100
90
80
70
60
50
8 12 1610 14 18 20 24 422 2 6 8
135
120
85
70
BP (mm Hg)
Li Y, et al. Hypertension 2007;50:333-339.
Owner
Numerous pathophysiological studies showed that adrenomedullin is a multifunctional vasoactive substance.It is a vasodilator. It may also promote natriuresis and modulate salt appetite, thirst and sympathetic activity. In humans, low levels of plasma adrenomedullin were associated with hypertension and target organ damage.In rodent models, adrenomedullin gene knockout may lead to high blood pressure, whereas adrenomedullin infusion or gene transfer had blood pressure lowing effect.Therefore we hypothesize that adrenomedullin might be a candidate gene for human hypertension.
The international database*
IDH (%) INH (%)
Chinese (n = 677) 4.9 # 10.9 #
South Africans (n = 201) 6.0 # 10.5 #
Japanese (n = 1038) 6.6 # 10.2 #
Eastern Europeans (n = 854) 9.1 7.9
Western Europeans (n = 3268) 13.9 6.0
# Compared to Western Europeans, P < 0.05* Staessen JA et al. J Hypertens 1994; 12: S1-S12.
Li Y, et al. Hypertension 2007;50:333-339.
Owner
In the next 3 slides, I will show you the characteristics of the participants. In 204 men and 223 women, age averaged 44 years. two third of men consumed alcohol and cigarrettes. About 20% of women drank alcohol but none smoked. The prevalence of hypertension was about 25% and only about 10% took antihypertensive drugs.
baPWV by ABP category
20
18
16
14
12
baPWV (m/s)
NT
14.6 16.1 16.2 17.4
IDH INH DNH
P<0.05 vs NT*
* Adjusted for sex, age, body height and pulse rate.Li Y, et al. Hypertension 2007;50:333-339.
IDACO: 单纯夜间高血压的预后
Fan HQ, et al. J Hypertens 2010; Epub.
Owner
In the next 3 slides, I will show you the characteristics of the participants. In 204 men and 223 women, age averaged 44 years. two third of men consumed alcohol and cigarrettes. About 20% of women drank alcohol but none smoked. The prevalence of hypertension was about 25% and only about 10% took antihypertensive drugs.
High prevalence and low control rates
High sodium and low potassium intakes
High night-time BP and low dipping
High stroke and increasing coronary event rates
High profile of CCBs
Incidence of Stroke in the Asian Pacific Region (2002)
127.6
105.9
97.3
72.6
68.4
65.5
57.0
56.3
43.2
42.4
41.0
39.9
31.0
0 20 40 60 80 100 120 140
China
Japan
South Korea
Vietnam
Myanmar
Laos
Indonesia
USA
Cambodia
Malaysia
Singapore
Thailand
Philippines
Incidence per 100,000
Atlas of Heart Disease and Stroke. MacKay J & Mensah G. 2004. Geneva. WHO Figures (not adjusted for age).
0
30
60
90
120
150
1985 1990 1995 2000 2005 2010 ( 年 )
脑卒中
冠心病
标化死亡率(1/10 万 )
冠心病 : 中国人群死亡重要原因
高血压导致心血管病的相对危险高达 3-4 倍在总的 CV 事件中， 23.7% 的急性冠心病事件归因于高血压
《中国心血管病报告 2005 》
CCBs vs. diuretics/-blockers: Fatal and nonfatal stroke CCBs vs. diuretics/-blockers: Fatal and nonfatal stroke
Old drugs CCBsTrials Number of events / patientsHetero-
geneity Odds ratios (95% CIs)
Difference (SD)
0CCBs better
1 2 3Old drugs better
MIDAS/NICS/VHAS
STOP2/CCBs
NORDIL
INSIGHT
ALLHAT/Amlodipine
ELSA
CCBs without CONVINCE p = 0.68
CONVINCE
All CCBs p = 0.39
15/1358
237/2213
196/5471
74/3164
675/15255
14/1157
1211/28618
118/8297
1329/36915
19/1353
207/2196
159/5410
67/3157
377/9048
9/1177
838/22341
133/8179
971/30520
–10.2% (4.8) 2p = 0.02
–7.6% (4.4) 2p = 0.07
Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.
High prevalence and low control rates
High sodium and low potassium intakes
High night-time BP and low dipping
High stroke and increasing coronary event rates
High profile of CCBs
Chinese hypertension guidelines
Diuretics
-blockers
Calcium channel blockers
Angiotensin converting enzyme inhibitors
Angiotensin receptor blockers
Syst-ChinaSyst-China
SystSystolic Hypertension in olic Hypertension in ChinaChina Trial Trial
J Hypertens 1998; 16:1823-1829.Arch Intern Med 2000; 160:211-220.
– 80 – 40 0 + 40%
Syst-China: Fatal and non-fatal endpointsSyst-China: Fatal and non-fatal endpoints
Liu LS et al. J Hypertens 1998;16:1823-1829.
Placebo
(n=1141
)Total mortality
CV mortality
Stroke mortality
All CV events
Fatal and non-fatal stroke
Active treatment
(n=1253)
Placebo better
82
44
20
94
59
61
33
10
74
45
Active treatment better
-39
-39
-58
-37
-38
82
44
20
94
59
61
33
10
74
45
FEVERFEVER
FFelodipine elodipine EveEvent nt RReduction Trialeduction Trial
J Hypertens 2005;23:2157-2172.
FEVER ： Fatal and nonfatal stroke (primary endpoint)
Liu LS et al. J Hypertens 2005;23:2157-2172.
00
22
44
66
88
1010
00 66 1212 1818 2424 3030 3636 4242 4848 5454 6060
↓↓27%27%
P=0.001P=0.001
HCTZHCTZ
Felodipine+HCTZFelodipine+HCTZ
Follow-upFollow-up （（ monthsmonths ））
Cumulative Cumulative
incidence incidence
(%)(%)
Chinese Hypertension Intervention Efficacy (CHIEF) ： General design
Hypertensive patients at high CV risk
(n=12,000)
Amlodipine 2.5 mg/d+telmisartan 40 mg/d
Amlodipine 2.5 mg/d+amiloride 1.25/ HCTZ 12.5 mg/d
Primary endpoint: CV death, stroke and MI
2y 4y3y1y0y
In Chinese, the number of hypertensive patients is huge, and the
control rate is low because of low awareness and insufficient
treatment.
The dietary Na+ is high, and the dietary K+ intake is low, making the
management of hypertension slightly different.
The night-time BP is high, and the nocturnal dipping is insufficient.
Isolated nocturnal hypertension is prevalent and confers CV risk.
Stroke, not MI, is the main CV complication of hypertension.
CCBs had been tested in trials in Chinese, and at present are the
mostly prescribed drug for hypertension, to prevent stroke with less
metabolic side effect than thiazides.
Summary
What is the optimized therapy for the Chinese population ?
Highly efficacious to control BP in a huge patient population.
Can be thiazides, but only in combination with an inhibitor of the renin system to prevent hypokalaemia.
Long acting to control BP at night and in the morning.
High safety and tolerability profile to safely control BP to a lowest tolerable level for long time or even the lifetime.
Thank you very much ！
