hypertension: improving treatment and control
TRANSCRIPT
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Improving Blood Pressure Treatment Improving Blood Pressure Treatment in the Community: Implications of the in the Community: Implications of the JNC7 Recommendations and ALLHAT JNC7 Recommendations and ALLHAT
Results Results
Nathan D. Wong, PhD, FACC Nathan D. Wong, PhD, FACCProfessor and DirectorProfessor and Director
Heart Disease Prevention ProgramHeart Disease Prevention ProgramUniversity of California, IrvineUniversity of California, Irvine
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Peripheral vascular disease
Morbidity
Disability
Renal disease
CADCHFLVHStroke
Hypertension
National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.
Hypertension: A Significant CV and Hypertension: A Significant CV and Renal Disease Risk FactorRenal Disease Risk Factor
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Nearly 1 in 3 adults (31%) in the US has hypertension
Fields LE et al. Hypertension. 2004;44:398-404.
Hypertension: Hypertension: How Big Is the Problem?How Big Is the Problem?
At Least 65 Million Americans Require At Least 65 Million Americans Require Treatment for HypertensionTreatment for Hypertension
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Risk of Cardiovascular Events Risk of Cardiovascular Events by Hypertensive Statusby Hypertensive Status
36-Year Follow-up in Patients Aged 35-64 36-Year Follow-up in Patients Aged 35-64 YearsYears
9.5
3.3 2.45.0
2.0 3.5 2.1
45.4
21.3
12.4
6.29.9
7.3
13.9
6.3
22.7
0
10
20
30
40
50
Men Women Men Women Men Women Men Women
Normotensive
Hypertensive
Coronary Disease Stroke Peripheral Arterial Disease
Cardiac Failure
Bie
nn
ial
Ag
e-A
dju
sted
Rat
e p
er 1
,000
Reprinted with permission from Kannel WB. JAMA. 1996;275:1571-1576.
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SBP-Associated Risks: MRFITSBP-Associated Risks: MRFIT
Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.
SBP versus DBP in Risk of CHD Mortality
Diastolic BP(mm Hg)
Systolic BP(mm Hg)
CHD Death Rate
100+90–99
80–8975–79
70–74<70 <120
120–139
140–159
160+
48.3
20.6
10.311.8
8.88.5
9.2
23.8
16.9
13.912.8
12.611.8
31.0
25.524.6 25.3
25.224.9
37.434.7
43.8
38.1
80.6
<40 40-49 50-59 60-69 70-79 80+Age (y)
17% 16% 16% 20% 20% 11%
Distribution of Hypertension Subtype in the untreated Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by AgeHypertensive Population in NHANES III by Age
ISH (SBP 140 mm Hg and DBP <90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg)IDH (SBP <140 mm Hg and DBP 90 mm Hg)
0
20
40
60
80
100
Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874.
Frequency of hypertension
subtypes in all untreated
hypertensives (%)
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Disease Relative Risk
Kidney failure (ESRD) 2.8Stroke 2.7Heart failure 1.5Peripheral vascular disease 1.8Myocardial infarction* =1.6Coronary artery disease 1.5
ESRD = end-stage renal disease; SBP 165 mm Hg.*Men only.
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part 1):587-594; Klag MJ et al. N Engl J Med. 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger. 1996;158:3779-3783; Neaton JD et al. Arch Intern Med. 1992;152:56-64.
Elevated SBP Alone Is Associated With Elevated SBP Alone Is Associated With Increased Risk of Cardiovascular and Renal Increased Risk of Cardiovascular and Renal
DiseaseDisease
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Prevalence, Awareness, Treatment, and Control Prevalence, Awareness, Treatment, and Control of Hypertension in US Adults 2003-2004 of Hypertension in US Adults 2003-2004 (Ong et al., Hypertension 2007; 49: 69-75)(Ong et al., Hypertension 2007; 49: 69-75)
30.7
52.1
33.328.2
58
35.2
28.5
53.7
35.439.1
55
28.9 27.8
48.3
26.5
0
10
20
30
40
50
60
Per
cen
t (%
)
Men Women White Black Hispanic
Prevalence Treatment Control
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Prevalence (%) of HTN in US Adults, by Disease Status Prevalence (%) of HTN in US Adults, by Disease Status (Wong et al, Arch Intern Med 2007, in press)(Wong et al, Arch Intern Med 2007, in press)
23.1
51.861.5
76.881.8
69.5 71.4 73.7 73
0
20
40
60
80
100
Pre
vale
nce
of
HT
N (
%)
No-Disease Dyslipidemia Mets DM CKD Stroke CHF PAD CAD
**P<0.01 when compared to No-Disease Group
**** **
****
****
Mean age (y): 53.5 59.3 54.8 60.5 76.1 65.9 68.2 69.3 67.2
**
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Treatment (%) of HTN in US Adults, by Disease Status Treatment (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press)(Wong et al., Arch Intern Med 2007, in press)
66.5 68 70.9
84
65.9
8983.4
73.4
89.3
0
20
40
60
80
100
Tre
atm
ent
of
HT
N (
%)
No-Disease Dyslipidemia Mets DM CKD Stroke CHF PAD CAD
*P<0.05, **P<0.01 when compared to No-Disease group
Treatment is in persons with HTN
****
** **
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Control (all treated) (%) of HTN in US Adults, by Disease Control (all treated) (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press)Status (Wong et al., Arch Intern Med 2007, in press)
64.6
49.3
63.7 61.2
42.2 34.9
48.846.7 50.3
0
20
40
60
80
100
Co
ntr
ol
of
HT
N (
%)
No-Disease Dyslipidemia Mets DM CKD Stroke CHF PAD CAD
**P<0.05**P<0.01 when compared to No-Disease Group
Control is in persons with HTN defined as BP < 140/90
If DM and CKD is based on BP<130/80 control is **35.3% and **23.2%, respectively.
If MetS is based on BP<130/85 control is **46.7%
*
** ****
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SBP mm Hg (Distance to Goal)
DBP mm Hg (Distance to Goal)
No Disease 154 (14) 93 (3)
Dyslipidemia 154 (19) 90* (7)
MetS 154 (16) 94 (5)
DM 149* (14) 87** (6)
CKD 155 (18) 87** (7**)
Stroke 155 (22*) 87** (6)
CHF 154 (22**) 89** (6)
PAD 157 (23**) 89* (7)
CAD 155 (21*) 90 (6)
Minimum BP distance from goal of < 140/90 in parenthesis, even with DM & CKD*p<0.05 **p<0.01 compared to no disease
Mean BP and Distance to Goal Among HTN Pts Not at Goal (Wong et al., Arch Intern Med 2007, in press)
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Blood Pressure ClassificationBlood Pressure Classification
Normal <120 and <80Prehypertension 120–139 or 80–89
Stage 1 HTN 140–159 or 90–99
Stage 2 HTN >160 or >100
BP Classification SBP mmHg DBP mmHg
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4-Year Progression To Hypertension: 4-Year Progression To Hypertension: The Framingham Heart StudyThe Framingham Heart Study
5
18
37
0
10
20
30
40
50
Optimal Normal High-Normal
Pat
ien
ts (
%)
(<120/80 mm Hg)
(130/85 mm Hg) (130-139/85-89 mm
Hg)Vasan, et al. Lancet 2001;358:1682-86
Participants age 36 and older
HOT Study: Significant Benefit FromHOT Study: Significant Benefit FromIntensive Treatment in the Diabetic SubgroupIntensive Treatment in the Diabetic Subgroup
Hansson L et al. Lancet. 1998;351:1755-1762.
0
5
10
15
20
25
90 85 80
Major cardiovascul
ar events/1,000 patient-
years
p=0.005 for trend
mm Hg
Target Diastolic Blood Pressure
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Benefits of Lowering BPBenefits of Lowering BP
Average Percent Reduction
Stroke incidence 35–40%
Myocardial infarction 20–25%
Heart failure 50% TROPHY Study ACC 2006: Even lowering BP in those with pre-HTN appears to reduce incidence of new HTN by up to 60%
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Preventable CHD Events from Control of Preventable CHD Events from Control of Hypertension in US AdultsHypertension in US Adults
(Wong et al., Am Heart J 2003; 145: 888-95)(Wong et al., Am Heart J 2003; 145: 888-95)
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37
31
56
21
11
39
21
0
10
20
30
40
50
60
PA
R%
/ N
NT
Men PAR% Women PAR% Men NNT Women NNT
Treatment to <140/90 mmHg Treatment to <120/80 mmHg
PAR% = population attributable risk (proportion of CHD events preventable), NNT = number needed to treat to prevent 1 CHD event ; <0.01 comparing men and women for PAR%
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Randomized DesignRandomized Designof ALLHATof ALLHAT
High-risk hypertensive patients
Consent / Randomize
(42,418)
Amlodipine
Chlorthalidone
Doxazosin
Lisinopril
Eligible for lipid-lowering
Not eligible for lipid-lowering
Consent / Randomize (10,355)
Pravastatin Usual care
Follow for CHD and other outcomes until death or end of study (up to 8 yr).
ALLHAT
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Baseline CharacteristicsBaseline Characteristicsand Follow-upand Follow-up
Baseline Follow-upN 42,418 Known alive 82%
Mean SBP/DBP 146 / 84 Confirmed dead 15%
Mean age, y 67 Lost / refused 3%
Black, % 36 Person-years(% obs/exp)
99%
Women, % 47
Current smoking % 22
History of CHD, % 26
Type 2 diabetes, % 36
On antihypertensive treatment, % 92
ALLHAT
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Doxazosin Arm Doxazosin Arm Terminated EarlyTerminated Early
• Futility of finding a significant difference for primary CHD outcome
• Statistically significant 20 percent higher rate of major secondary endpoint, combined CVD outcomes (80% higher rate of heart failure)
ALLHAT
Hypertension. 2003;42:239-246.
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BP Results by Treatment GroupBP Results by Treatment Group
Compared to chlorthalidone:
SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg).
Compared to chlorthalidone:
DBP significantly lower in the amlodipine group (~1 mm Hg), similar in the lisinopril group.
ALLHAT
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Years to CHD Event0 1 2 3 4 5 6 7
Cumulative CHD Event Rate
0
.04
.08
.12
.16
.2
Number at Risk: Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209 Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195
Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group
RR (95% CI) p value
A/C 0.98 (0.90-1.07) 0.65
L/C 0.99 (0.91-1.08) 0.81
ALLHAT
ChlorthalidoneAmlodipineLisinopril
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Subgroup ComparisonsSubgroup Comparisons
Results were consistent across age, race, gender, and baseline diabetes subgroups, except:
– Stroke
• Black L/C RR (95% CI) = 1.40 (1.17 – 1.68)
• Non-Black L/C RR (95% CI) = 1.00 (0.85 – 1.17)
– Combined CVD
• Black L/C RR (95% CI) = 1.19 (1.09 – 1.30)
• Non-Black L/C RR (95% CI) = 1.06 (1.00 – 1.13)
ALLHAT
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Nonfatal MI + CHD Death – Subgroup Comparisons – RR (95% CI)
Amlodipine Better Chlorthalidone Better
0.50 1 2
Non-Diabetic 0.97 (0.86, 1.09)
Diabetic 0.99 (0.87, 1.13)
Non-Black 0.97 (0.87, 1.08)
Black 1.01 (0.86, 1.18)
Women 0.99 (0.85, 1.15)
Men 0.98 (0.87, 1.09)
Age>=65 0.97 (0.88, 1.08)
Age <65 0.99 (0.85, 1.16)
Total 0.98 (0.90, 1.07)
Lisinopril Better Chlorthalidone Better
0.50 1 2
Non-Diabetic 0.99 (0.88, 1.11)
Diabetic 1.00 (0.87, 1.14)
Non-Black 0.94 (0.85, 1.05)
Black 1.10 (0.94, 1.28)
Women 1.06 (0.92, 1.23)
Men 0.94 (0.85, 1.05)
Age >= 65 1.01 (0.91, 1.12)
Age < 65 0.95 (0.81, 1.12)
Total 0.99 (0.91, 1.08)
ALLHAT
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Prospective Studies Collaboration, Lancet 2002;360:1903-13Prospective Studies Collaboration, Lancet 2002;360:1903-13
Predicted Cause-specific MortalityPredicted Cause-specific Mortalityfor 2 mm Hg lower SBPfor 2 mm Hg lower SBP
CHDCHD -4 to -7%-4 to -7%StrokeStroke -4 to -10%-4 to -10%Heart failureHeart failure -5 to -7%-5 to -7%
Higher numbers for younger Higher numbers for younger hypertensiveshypertensives
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Amlodipine / Chlorthalidone Lisinopril / Chlorthalidone
CHD 0.98 (0.91, 1.08) 0.99 (0.91, 1.08)
Death 0.96 (0.89, 1.02) 1.00 (0.94, 1.08)
CCHD 1.00 (0.94, 1.07) 1.05 (0.98, 1.11)
Stroke 0.93 (0.82, 1.06) 1.15 (1.02, 1.30)
CCVD 1.04 (0.99, 1.09) 1.10 (1.05, 1.16)
HF 1.38 (1.25, 1.52) 1.19 (1.07, 1.31)
Amlodipine Chlorthalidone Better Better
0.50 1 2Lisinopril Chlorthalidone Better Better
0.50 1 2
Summary of OutcomesRelative Risks and 95% CIALLHAT
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Fasting Glucose ResultsFasting Glucose Results
Chlorthalidone Amlodipine Lisinopril
Serum fasting glucose – mmol/L, mean (sd)
Among baseline nondiabetics with baseline <126 mg/dL – mean (SD)
Baseline 93.1 (11.7) 93.0 (11.4) 93.3 (11.8)
4 Years 104.4 (28.5) 103.1 (27.7) 100.5 (19.5)*
Diabetes Incidence (follow-up fasting glucose 126 mg/dL)
4 Years 11.6% 9.8%* 8.1%*
* p<.05 compared to chlorthalidone
ALLHAT
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• Outcome results were similar in diabetic and nondiabetic participants
• For both diabetic and nondiabetic participants, there were significant advantages for the diuretic arm
ALLHAT ALLHAT Results by Baseline ALLHAT Results by Baseline Diabetic StatusDiabetic Status
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Effect of 2-Year Changes in Fasting Glucose on ALLHAT Effect of 2-Year Changes in Fasting Glucose on ALLHAT EndpointsEndpoints
(Cox Regressions Beginning at 2 Years)(Cox Regressions Beginning at 2 Years)
Per 10-Unit of Increase in Fasting Glucose (Baseline to 2 Years)
Endpoint Hazard Ratio 95% CI P
CHD 1.022 0.979 – 1.066 0.327
CCHD 1.004 0.968 – 1.042 0.824
Stroke 0.986 0.909 – 1.069 0.727
CCVD 1.003 0.971 – 1.036 0.836
Heart failure 1.000 0.939 – 1.066 0.988
ESRD 1.035 0.921 – 1.164 0.561
Total mortality 0.990 0.948 – 1.035 0.664
ALLHATALLHAT
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Diuretics, Potassium,Diuretics, Potassium,and Glucoseand Glucose
• Based on 40+ years’ evidence, potassium depletion is a major factor relating thiazide treatment and abnormal glucose.
• Both reduced insulin release and decreased insulin sensitivity have been demonstrated.
• More attention than is often given to preventing or reversing hypokalemia is warranted, especially in patients at risk of diabetes.
Reference: Wilcox CS. Seminars in Nephrology, 1999;19:557-68.
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Large Hypertension Trials Comparing Two or More Large Hypertension Trials Comparing Two or More Regimens: CVD or CV MortalityRegimens: CVD or CV Mortality
TrialTrial n n BP BPΔΔ OutcomesOutcomes
CAPPPCAPPP 10,985 +3/+1 10,985 +3/+1 captopril captopril not superior to not superior to D/BBD/BB
NORDILNORDIL 10,881 +3/0 10,881 +3/0 diltiazemdiltiazem not superior to not superior to D/BBD/BB
CONVINCECONVINCE 16,602 0/+1 16,602 0/+1 verapamil verapamil not superior to not superior to D/BBD/BB
STOP-2STOP-2 6,628 0/-1 6,628 0/-1 isradipine/felodipine &isradipine/felodipine &
0/00/0 ACEIsACEIs not superior to not superior to D/BBD/BB
INSIGHTINSIGHT 6,592 0/0 6,592 0/0 nifed GITSnifed GITS not superior to not superior to diureticdiuretic
LIFELIFE 9,193 9,193 +1/0 +1/0 losartanlosartan superior to superior to atenololatenolol
ANBP-2ANBP-2 6,083 +1/0 6,083 +1/0 ACEIsACEIs not superior to not superior to diureticsdiuretics
ALLHATALLHAT 42,418 -3/-1 42,418 -3/-1 chlorthalidonechlorthalidone superior to superior to doxazosindoxazosin, ,
-1/+1,-2/ 0 -1/+1,-2/ 0 amlodipineamlodipine (HF only), (HF only), lisinoprillisinopril
INVESTINVEST 22,576 0/ 0 22,576 0/ 0 verapamilverapamil ( (++trandolapril) equivalenttrandolapril) equivalent
to to atenololatenolol ( (++HCTZ)HCTZ)
VALUEVALUE 15,313 15,313 +2/+2 +2/+2 valsartanvalsartan not superior to not superior to amlodipineamlodipine
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35
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Large, controlled trials have shown similar Large, controlled trials have shown similar mortality or morbidity reductions with:mortality or morbidity reductions with:
Bendrofluazide (MRC)Bendrofluazide (MRC)
Chlorthalidone (SHEP, HDFP)Chlorthalidone (SHEP, HDFP)
Hydrochlorothiazide (VA, Oslo, Australian)Hydrochlorothiazide (VA, Oslo, Australian)
Indapamide (PATS, PROGRESS)Indapamide (PATS, PROGRESS)
HCTZ/amiloride (MRC-O, STOP-H)HCTZ/amiloride (MRC-O, STOP-H)
HCTZ/triamterene (EWPHE)HCTZ/triamterene (EWPHE)
ConclusionConclusionIndependent trial findings support the view Independent trial findings support the view
that all thiazide diuretics are beneficialthat all thiazide diuretics are beneficial
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angiotensin-converting enzyme inhibitors (ACEI); angiotensin receptor blocker (ARB);angiotensin-converting enzyme inhibitors (ACEI); angiotensin receptor blocker (ARB); myocardial infarction (MI); myocardial infarction (MI); cardiovascular (CV); heart failure (HF); left ventricular hypertrophy (LVH). cardiovascular (CV); heart failure (HF); left ventricular hypertrophy (LVH).
Yusuf S et al. Yusuf S et al. N Engl J MedN Engl J Med. 2000;342:145-153; The CONSENSUS Trial Study Group. . 2000;342:145-153; The CONSENSUS Trial Study Group. N Engl J MedN Engl J Med. 1987;316:1429-1435; . 1987;316:1429-1435; The SOLVD Investigators. The SOLVD Investigators. N Engl J Med. N Engl J Med. 1991;325:293-302; 1991;325:293-302; Granger CB et al. Granger CB et al. LancetLancet. 2003;362:772-776; . 2003;362:772-776; Dahlof B et al.Dahlof B et al. Lancet.Lancet. 2002;359:995-1003; 2002;359:995-1003; Cohn JN et al. Cohn JN et al. N Eng J Med.N Eng J Med. 2001;345:1667-1675. 2001;345:1667-1675.
HOPECONSENSUSPlacebo (n=4652)Ramipril (n=4645)
Placebo (n=126)Enalapril (n=127)
LIFEAtenolol (n=4588)Losartan (n=4605)
CHARM-Added
MI, stroke, or CV death in high-risk patients
Total mortalityin severe HF
Death, MI, or stroke in patients aged 55–80 years with hypertension and LVH
Rel
ati
ve
Ris
k R
ed
uct
ion
, %
CV death or HF hospitalizationin patients with chronic HF
Placebo (n=1272)Candesartan (n=1276)
ACEIs
SOLVDPlacebo (n=1284)Enalapril (n=1285)
Mortality in chronic HF
Val-HeftValsartan (n=2511)Placebo (n=2499)
All cause mortality and morbidity in patients with HF
ACEIs and ARBs Reduce ACEIs and ARBs Reduce Cardiovascular Morbidity and Cardiovascular Morbidity and
MortalityMortality
ARBs
–40
–30
–20
–10
0
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Implications for Your Practice Implications for Your Practice and Your Patientsand Your Patients
• The blood pressure goal for most patients with hypertension is <140/90 mm Hg.
• Initial drug therapy for most should be either thiazide-type diuretic alone or combined with other drug classes.
• Most patients with uncontrolled Stage 1 or Stage 2 hypertension should experience better blood pressure control and better long term CVD risk when the medication regimen includes a thiazide-type diuretic.
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Algorithm for Treatment of HypertensionAlgorithm for Treatment of Hypertension
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension(SBP 140–159 or DBP 90–99
mmHg) Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling Indications
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
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AHA Scientific Statement Recommendations: AHA Scientific Statement Recommendations: General CVD Prevention, High CAD Risk, Stable and General CVD Prevention, High CAD Risk, Stable and
Unstable Angina, NSTEMI, STEMI, LVDUnstable Angina, NSTEMI, STEMI, LVD (Circulation 2007; 115: 2761-2788) (Circulation 2007; 115: 2761-2788)
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AHA 2007 Statement Recommendations AHA 2007 Statement Recommendations
• A target BP of <130/80 mmHg is reasonable for individuals with any of the following (Class IIa, level of evidence B):– Diabetes mellitus– Chronic renal disease– Coronary artery disease (CAD)– CAD risk equivalents– Carotid artery disease– Peripheral artery disease– Abdominal aortic aneurysms– High risk pts defined as >=10% 10-year risk
from FRS
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Compelling Indications for Compelling Indications for Individual Drug ClassesIndividual Drug Classes
Compelling Indication Initial Therapy Option
Heart failure THIAZ, BB, ACEI, ARB, ALDO ANT
Post myocardial infarction
BB, ACEI, ALDO ANT
High CAD Risk THIAZ, BB, ACEI, CCB
Diabetes THIAZ, BB, ACEI, ARB, CCB
Chronic kidney disease ACEI, ARB
Recurrent stroke prevention
THIAZ, ACEI
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Rahuel J et al. Rahuel J et al. J Struct Biol.J Struct Biol. 1991;107:227-236. 1991;107:227-236.
• Angiotensinogen
Aliskiren binds to a pocket Aliskiren binds to a pocket in the renin molecule,in the renin molecule,blocking angiotensinogenblocking angiotensinogenfrom being cleaved by renin from being cleaved by renin
Renin Inhibition With Renin Inhibition With AliskirenAliskiren
Binding of Angiotensinogen Binding of Angiotensinogen PreventedPrevented
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VasoconstrictionVasoconstriction RemodellingRemodelling
VesselsVessels
KidneyKidney
HeartHeart
(Pro)Renin Receptor(Pro)Renin ReceptorActions:Actions:• Binding of (Pro)ReninBinding of (Pro)Renin• Increased renin Increased renin
catalytic activitycatalytic activity• Activates VSMC ERK1/2Activates VSMC ERK1/2
Aliskiren Suppresses the Aliskiren Suppresses the Entire System—Targets the Entire System—Targets the
Point of ActivationPoint of Activation
ReninRenin
Ang IIAng II
AngiotensinogenAngiotensinogen
ARBsARBs
ATAT11 receptor receptor
AldosteroneAldosterone
Ang III + IVAng III + IV
ACEACEACEIsACEIs
Non-ACENon-ACEpathwayspathways
Ang IAng I
Target cellTarget cell
AliskirenAliskiren
(Pro)Renin(Pro)Reninreceptorreceptor
renin-angiotensin-aldosterone system (RAAS); vascular smooth muscle cells (VSMC); extracellular singal-regulated renin-angiotensin-aldosterone system (RAAS); vascular smooth muscle cells (VSMC); extracellular singal-regulated kinases (ERK 1/2); angiotensin (Ang); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme inhibitor kinases (ERK 1/2); angiotensin (Ang); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme inhibitor (ACEI); angiotensin receptor blockers (ARB); type 1 angiotensin II receptor (AT(ACEI); angiotensin receptor blockers (ARB); type 1 angiotensin II receptor (AT 11) .) .
AliskirenAliskiren
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Lifestyle Modifications Lifestyle Modifications
• Most patients will experience better control if they modify diet and exercise.
• Physician advice sometimes works and should always be given along with a follow-up visit appointment to monitor both blood pressure and lifestyle change efforts.
• Most of us do not do lifestyle counseling beyond simple advice and admonishment – the time factor is a problem.
• Nevertheless, lifestyle modification is at the top of the JNC7 algorithm.
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Lifestyle ModificationLifestyle Modification
ModificationApproximate SBP reduction (range)
Weight reduction 5-20 mmHg / 10 kg weight loss
Adopt DASH eating plan 8-14 mmHg
Dietary sodium reduction 2-8 mmHg
Physical activity 4-9 mmHg
Moderation of alcohol consumption
2-4 mmHg
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The Japanese Diet and LifestyleThe Japanese Diet and Lifestyle
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Keys to Physician Influence Keys to Physician Influence in Lifestyle Modificationin Lifestyle Modification
• Advice giving and follow-up monitoring are a minimum (many pts are not adequately titrated to goal BP)
• Some evidence that brief behavioral counseling aimed at matching messages to patient readiness to change and eliciting the patient’s own motivation to change can move the patient along a continuum of change
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Physician Influence in Lifestyle Physician Influence in Lifestyle Modification- What to DoModification- What to Do
PICMPICM
• Permission: Ask the patient for permission to talk about lifestyle change and get preference for beginning with diet or exercise
• Interest: Ask the patient about readiness to change – How interested are you on a scale of 1-10. Ask why they are not a lower number – to elicit a motivational statement from the patient.
• Confidence: Ask how sure they are that they can do the behavior – again ask why not a lower number
• Match a message to interest and confidence
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Summary: For better long-term CVD Summary: For better long-term CVD risk for your patientsrisk for your patients
• Focus on blood pressure control for both SBP and DBP (<140/90 mm Hg - <130/80 for patients with diabetes or chronic renal disease)
• Follow the JNC7 treatment guidelines: Use a thiazide-type diuretic as first line treatment and in combination for uncontrolled HTN
• Do your part to disseminate these evidence-based guidelines
• Make a renewed effort to encourage lifestyle change
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Tools to Enhance BP ControlTools to Enhance BP Control
For use with patients: • Physician-patient hypertension treatment planning pad for
exam rooms• Poster for exam rooms • The DASH Eating Plan (also on CD & NHLBI.ORG)• Brief behavioral counseling steps and patient monitoring
tools
For your reference:• Pocket card (palm format downloadable from ALLHAT.ORG)• ALLHAT results paper; Setting the Record Straight paper• Newsletter• JNC7 reference card (also on CD & NHLBI.ORG)
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Web siteWeb sitewww.nhlbi.nih.gov/www.nhlbi.nih.gov/
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DASH Fact SheetDASH Fact Sheet
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Your Guide to Lowering Your Guide to Lowering Blood PressureBlood Pressure
56
Reference CardReference Card
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Thank you for your attention!
For more information
contact the UCI Heart Disease
Prevention Program at:
www.heart.uci.edu
949-824-5561