0
* Estimated deaths by 2020
10
20
30
40
50
60
70
80
A rise in obesity
Higher prevalence of diabetes Increased cardiovascular disease
Tobacco epidemic
WHO. The World Health Report, 1999. Neal B, et al. Eur Heart J 2002; 4(Suppl. F): F2-F6.
Age and gender Family history of CAD or other atherosclerotic disease at early age (<55 years men, <65 years women) Personal history of CAD or other atherosclerotic disease
Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2003; 24: 1601-10.
Remodelling
Atherosclerosis LVH
Ventricular dilatation
Prevalence of Hypertension:
Over The World
1 among 4 person in the range of age 18-50 yo 1 from 2 person who over 50 yo Cheng et al in Taiwan reported the data of 6,2%
In Philippines, from 80 M Filipinos, 17% prevalence among those over 15 years 6.8 million hypertensives
Hypertension in INDONESIA
Based on Survey of Household Health (SKRT 1995) is 8,3 % per 100 population Women > men Based on bordeline hypertension criteria (140/90159/94 mmHg), the prevalence is 4,8-18,8%. Based on WHO report for last 10 years, hospitalized patient due to hypertension in Semarang increased by 10 fold. In North Sumatera demonstrate of 3 - 9,17% from the population
Normal
High normal Grade 1 Hypertension (mild)
120-129 / 80-84
130-139 / 85-89 140-159 / 90-99
120-129 /80-84
130-139 / 85-89 140-159 / 90-99
Prehypertension
Prehypertension Stage 1 Hypertension
160-179 /100-109
> 160 / > 100 > 180 / >110 > 140 < 90
Stage 2 Hypertension
10
8 6 4 2 0 0
No. at risk Optimal Normal High Normal
Normal
Optimal
Time (years)
995 1039 879 973 1012 857
10
12
Meta-Analysis: Lower Systolic BP Results in Slower Rates of Decline in GFR in Patients with/out DM
SBP (mm Hg)
130
0
134
138
142
146
150
154
170
180
GFR (mL/min/y)
-2
Untreated hypertension
-14
Parving HH et al. Br Med J. 1989. Viberti GC et al. JAMA. 1993. Klahr S et al. N Eng J Med. 1994. Hebert L et al. Kidney Int. 1994. Lebovitz H et al. Kidney Int. 1994. Moschio G et al. N Engl J Med. 1996. Bakris GL et al. Kidney Int. 1996. Bakris GL. Hypertension. 1997. GISEN Group. Lancet. 1997.
CVD mortality
RF adjusted cardiovascular 1.66[1.042.64] relative risk
CAD mortality
2.35[1.035.35] ***p<0.001 v uncontrolled group
(LANCET 2000)
35 40 % mean reduction in stroke
20 25 % decrease in MI incidence
> 50 % reduction in CHF
BENEFITS OF BP LOWERING
Stage I Hypertensive Patients with CVD Risk Factors Sustained 12-mmHg decrease in systolic BP for 10 years prevents 1 death for every 11 patients treated
Stage I Hypertensive Patients with CVD or TOD Sustained 12-mmHg decrease in systolic BP for 10 years prevents 1 death for every 9 patients treated
BENEFITS OF BP LOWERING
Adapted from THE JNC7 REPORT 2003
Antihypertensive Therapy
Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2003; 24: 1601-10.
Verapamil (1963)
Furosemide (1964) Propanolol (1965)
1970
Nifedipin (1975)
Diltiazem (1980) 1980 Captopril (1981) Amlodipine (1987) Bisoprolol (1988) Losartan (1995) 1990 Valsartan
Prazosin (1977)
AT-antagonists/ARB
2000 ?
Lifestyle Modification
Lifestyle Modification Aproximate SBP Reduction
___________________________________________________ ___________
Physical activity
Moderation of alcohol consumption
4- 9 mmHg
2- 4 mmHg
Choose between Single agent at low dose 2 drug combination at low dose If goal BP not achieved Previous agent at full dose Switch to different Agent at low dose Previous combination at full dose Add a third drug at low dose
Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg) 2-drug combination for most
Diuretics
Mean arterial pressure Lipid profile Insulin resistance Primary prevention
Unfavourable or
Secondary prevention
Limited
Decrease Increase No effect Evidence for efficacy
Beta-Blockers
Mean arterial pressure Lipid profile Insulin resistance Primary prevention
Unfavourable
(MI)
Secondary prevention
Secondary prevention
Angiotensin-Receptor Blockers
Mean arterial pressure Lipid profile Insulin resistance Primary prevention
Neutral Some evidence
Secondary prevention
Some evidence
Decrease
ACE Inhibitors
Mean arterial pressure Lipid profile Insulin resistance Primary prevention
Neutral
Secondary prevention
MECHANISM OF ACTION :
Angiotensinogen
K in in o g e n K a lik r e in
Angiotensin I ACE
B r a d ik in in
ACE
ACE INHIBITOR
Angiotensin II
P e p tid a In a k tif
Lipid profile
Insulin resistance Primary prevention Secondary prevention
Neutral
Neutral
Some evidence Some evidence
(non-DHPs) (non-DHPs)
Limited
JNC VII - Basis for The Compelling Indications for Individual Drug Classes
High-risk condition with compelling indications Diuretic
HF Post MI High Coronary disease Risk DM Chronic Kidney Disease Recurrent Stroke prevention
Recommended drugs
Beta Blocker
AR ACE I B
Beta-blockers
Alpha-blockers
ACE inhibitors
Guidelines Committee. J Hypertens 2003; 21: 1011-53.
ATLAS
ATLAS: Conclusion
A non-significant 8% risk reduction in primary endpoint of all-cause mortality with high dose lisinopril A highly statistically significant 12% risk reduction in secondary endpoint of all-cause mortality & all-cause hospitalization with high dose lisinopril. An 8-10% risk reduction in all other secondary endpoints
Both high and low doses of lisinopril were well tolerated; adverse events were not unexpected and were within label
Additional costs associated with high dose lisinopril were offset by the reduction costs associated with hospitalizations
ATLAS has established the therapeutic strategy for physicians to increase the dose of lisinopril in heart failure
GISSI-3
Gruppo Italiano per lo Studio della Sopravvienza nellInafarto Miocardico 3 Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction GISSI-3 Study Group Lancet 1994; 343: 1115-1122
GISSI-3: Results
TOLERABILITY All therapies were well tolerated although persistent hypotension and renal dysfunction were significantly more common with lisinopril However, neither were associated with an increase in mortality or in severe renal failure
OTHER RESULTS The 11% reduction in the risk of death at 6 weeks translates into a saving of 8 lives per 1,000 patients treated This is clinically meaningful since it is achieved in patients already receiving other treatment know to improve survival following an MI (thrombolytics, aspirin and beta-blockers) Lisinopril therefore provides an additional life-saving benefit over an above that already achieved with standard coronary care unit treatments
GISSI-3 Study Group. Lancet 1994; 343: 1115-1122
EUCLID
EUrodiab Controlled trial of Lisinopril in Insulin dependent Diabetes
Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependant diabetes and normoalbuminurea or microalbuminurea EUCLID Study Group
EUCLID
EUrodiab Controlled trial of Lisinopril in Insulin dependent Diabetes
Morbidity and mortality are high in IDDM (Type 1 diabetes) due to renal and cardiovascular complications. These are related to urinary albumin content ACE inhibitors benefit patients with raised albumin excretion but their effect on normo-albuminuria is unknown EUCLID investigated whether once-daily lisinopril reduced the progression of renal disease in patients with Type 1 diabetes
EUCLID Study Group. Lancet 1997; 349: 1787-1792
EUCLID: Conclusions
In Type 1 diabetes patients without hypertension Lisinopril slows the progression of renal disease in normoalbuminuric and microalbuminuric patients
Greatest benefits were seen in microalbuminuric patients
EUCLID
EUrodiab Controlled trial of Lisinopril in Insulin dependent Diabetes Effect of lisinopril on progression of retinopathy in normotensive people with Type 1 diabetes
EUCLID
Retinopathy data
Retinopathy, a diabetic complication which shares the risk factors of nephropathy Diabetic retinopathy is the leading cause of blindness in people aged 30-69 years
Retinopathy Assessment
Retinopathy was assessed from two 45-50 degree fundus photographs from each eye, using the EURODIAB-Hammersmith grading system
Retinopathy was classified into 5 groups (none to proliferative) according to the worst eye Retinal photographs were taken at baseline and 24 months, and were graded by a single observer, who was blinded concerning treatment status
Chaturvedi N, Sjolie A-K, Stephenson JM et al. Lancet 1998; 351: 28-31
In Type 1 diabetes patients without hypertension lisinopril slows the progression of retinopathy independent of the degree of renal disease
Achieving Success in
Management of Hypertension
Poor compliance Under aggressiveness of physician in HT treatment Wrong medication ; not proper combination ; medication interfering risk with BP control White coat HT Pseudo HT Secondary HT
(Noncompliance is characterized by patients who Meredith PA: Clinical Relevance of Pharmacokinetics in Cardiovascular Therapy Symposium, February 25, 1994. take 40-80% of doses and by drug holidays)
Antihypertensive effects Safety Patient acceptance Cost Number of doses per day Need for laboratory follow-up Mechanism of action Potential interaction with other drugs Additional salutary effects
Epstein M, Oster JR. In: Hypertension. A Practical Approach. 1984:112-118