1. What Is the Optimal Systolic Blood Pressure Goal in Hypertension Therapy?
William C. Cushman, MD
Chief, Preventive Medicine Section,
Memphis VA Medical Center
Professor, Preventive Medicine, Medicine, and Physiology
University of Tennessee Health Science Center

2. JNC 7: BP Classification
11/29/2017 6:33 PM
JNC 7: BP Classification
BP Level (mm Hg)*
Category
Systolic
Diastolic
< 120
and < 80
Normal or
Pre-hypertension or
Stage 1 Hypertension
≥ 160
or ≥ 100
Stage 2 Hypertension
JNC 7 is a detailed document produced by a committee that applied broad expertise in developing a valuable guideline for all clinicians who treat patients with high BP.
In contrast to the classic concept that normal BP is < 140/90 mm Hg, normal BP in adults is defined as < 120/80 mm Hg, above which the risk of CV events increases.
Pre-hypertension, or high-normal BP, is 120/80 mm Hg to 139/89 mm Hg, and risk in patients in this group can be lowered by lifestyle modification comprising weight reduction, reduced sodium intake, regular physical activity, and avoidance of excessive alcohol consumption.
This new guideline presents a number of updated concepts that improve our understanding of hypertension as a CV risk factor and current approaches to treatment. Thus, clinical trials have demonstrated that antihypertensive therapy can reduce the incidence of stroke by 35%-40%, MI by 20%-25%, and heart failure by more than 50%.
JNC 7 emphasizes that a clinician's judgment is foremost in managing hypertensive patients. The guidelines present the scientific basis of antihypertensive therapy and the physician's application of this evidence to individual patients represents the art of medicine. Adherence to these principles can diminish the continuing "knowledge-practice gap" in the management of CV risk factors and contribute to the ultimate goal of stemming the tide of CVD.
Reference
Chobanian AV et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:
*Use higher value for classification.
Chobanian AV et al. JAMA. 2003;289:
L:\CL Presentations MCS\Hpertension\HypertensionAroundtheWorld.ppt

3. Prevalence of Blood Pressure Categories in US Adults ≥20 Years of Age
(NHANES )
BP Category
Prevalence
Normal
39%
Prehypertension
31%
Hypertension
29%
Greenlund, Croft, Mensah (CDC). Arch Intern Med. 2004;164:2113f

4. Goal BP for Hypertensive Patients (mm Hg)
JNC VA-DoD
Most patients <140/ <140/90
Diabetes <130/ <140/80
CKD <130/ <140/90_
CVD (AHA): <130/80

5. Clinical Epidemiology of Hypertension in the U.S. 1988-2008
~75 million Americans have HTN
JAMA 2010;303:2043–2050

6. HTN Control Rates in VA < or ≤ 140/90 mm Hg* FY08 & 09 Target 75%
2004 < or = 140/90 = 70% n = 4,580
2003 < or = 140/90 = 68% n = 26,358
2002 < 140/90 = 55% n = 26,747
2001 < 140/90 = 51% n = 47,102
2000 < 140/90 = 46% n = 34,076
*<140/90 mm Hg in
data from:
VA OQP
5% drop (68% to 63%) in 2003 when < 140/90 calculated
6% drop (73% to 67%) in 2004 when < 140/90 calculated 6

7. High Blood Pressure and CHD Risk
Lancet 2002; 360: 1903–13

8. High Blood Pressure and Stroke Risk
Lancet 2002; 360: 1903–13

9. Why is it important not to intensify medications to reduce BP below the level proven in trials?
Treating to lower BP levels may be harmful (J-curve?) 9

10. Incidence of the primary outcome (first occurrence of death, nonfatal MI, or nonfatal stroke) by SBP and DBP strata in INVEST Trial
Messerli, F. H. et. al. Ann Intern Med 2006;144:

11. Why is it important not to intensify medications to reduce BP below the level proven in trials?
Treating to lower BP levels may be harmful (J-curve?)
If neither beneficial nor harmful
Adding unneeded drugs wastes patients’ and payers’ resources and time:
More visits, drugs, monitoring, treating AEs
More drugs may contribute to reduced adherence to other evidence-based drug treatments (e.g., statins and aspirin) 11

12. Systolic BP in Trials Testing SBP Goals: SHEP, Syst-Eur, Syst-China, HYVET
Entry SBP
Goal SBP <148* < < <150
Baseline
Achieved : drug
Achieved: placebo
* Integrated SBP goal, personal communication, Barry Davis
SBP = systolic blood pressure

13. What should the SBP treatment goal be in patients with hypertension?
Clinical trial evidence is very consistent for SBP goal <150 mm Hg.
Indirect evidence, mostly from trials with DBP goals, suggest SBP goal <140 mm Hg may be reasonable.
Public health: SBP goal <140 mm Hg has been recommended by many guidelines for several decades.

14. What should the Systolic BP treatment goal be in patients with diabetes mellitus?

15. Elevated SBP in Type 2 Diabetes Increases Cardiovascular Risk
Elevated SBP increases risk of CV death almost twofold in diabetic vs nondiabetic patients
Cardiovascular Mortality Rate per 10,000 Patient-Years
SBP (mm Hg)
Nondiabetic patients
Diabetic patients
250
200
150
100 50
<120
120–139
140–159
160–179
180–199
³200
MRFIT
Points of Emphasis / Key Messages
The risk of cardiovascular death is substantially increased in patients with type 2 diabetes and comorbid elevated SBP. For an SBP of 120 to 139 mm Hg, concurrent diabetes is equivalent to adding 40 mm Hg to the systolic pressure.
In addition, MRFIT demonstrated that SBP (as well as elevated serum cholesterol levels and cigarette smoking) is a significant predictor of mortality in men with and without diabetes.
The Multiple Risk Factor Intervention Trial (MRFIT) enrolled 361,662 men 35 to 37 years of age. A total of 5625 were receiving treatment for diabetes; the remaining 356,037 did not have diabetes.
The study did not classify diabetes as insulin-dependent or non-insulin-dependent (NIDDM), but because of the participants’ age, more than 90% were assumed to have NIDDM. 
Men whose SBP was ³180 mm Hg had nearly twice the risk of CV mortality if they had diabetes. If SBP was 140 to 179 mm Hg, the risk was more than twice that of men with diabetes. 
Reference
Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr
cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.
Diabetes Care. 1993;16:
Stamler J et al. Diabetes Care. 1993;16:

17. ACCORD Double 2 x 2 Factorial Design
Lipid
BP (Systolic)
Placebo Fibrate
Intensive
<120 mm Hg
Standard
<140 mm Hg
Intensive
Glycemic
Control
1383
1374
1178
1193
5128
Standard
Glycemic
Control
1370
1391
1184
1178
5123
2753
2765
2362
2371
10,251
5518
4733*

18. ACCORD BP Trial Design
Primary BP question: does a therapeutic strategy targeting systolic blood pressure (SBP) <120 mm Hg reduce CVD events compared to a strategy targeting SBP <140 mm Hg in patients with type 2 diabetes at high risk for CVD events?
4733 participants with type 2 diabetes were randomly assigned to intensive (SBP <120 mm Hg) or standard (SBP <140 mm Hg) therapy.
Mean follow-up: 4.7 years.
94% power for 20% reduction in primary event rate, assuming standard group rate of 4%/yr and 5.6 yrs follow-up.

19. Primary and Secondary Outcomes for ACCORD BP Trial
Primary outcome -- composite of:
Nonfatal MI, nonfatal stroke, CVD death
Secondary outcomes:
Expanded macrovascular outcome: 1º + any revascularization and hospitalization for HF
major CAD events
nonfatal MI
combined fatal and nonfatal stroke
nonfatal stroke
total mortality
CV mortality HF 19

20. ACCORD BP Trial Eligibility
Stable Type 2 Diabetes >3 months
HbA1c 7.5% to 11% (or <9% if on more meds)
High CVD risk = 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
Systolic blood pressure
130 to 160 mm Hg (if on 0-3 meds)
161 to 170 mm Hg (if on 0-2 meds)
171 to 180 mm Hg (if on 0-1 meds)
Urine protein <1.0 gm/24 hours or equivalent
Serum Creatinine ≤1.5 mg/dl

21. ACCORD BP Protocol
Many drugs/combinations provided to achieve goal BP according to randomized assignment
Intensive Intervention:
2-drug therapy initiated: thiazide-type diuretic + ACEI, ARB, or b- blocker
Drugs added and/or titrated at each visit to achieve SBP <120 mm Hg
At periodic “milepost” visits: addition of another drug “required” if not at goal
Standard Intervention:
Intensify therapy if SBP ≥160 mm 1 visit or ≥140 mm 2 consecutive visits
Down-titration if SBP <130 mm 1 visit or <135 mm 2 consecutive visits

22. Baseline Characteristics
Mean or %
Age (yrs) 62
Blood Pressure (mm Hg)
139/76
Women % 48
On Antihypertensive % 87
2° prevention % 34
Creatinine (mg/dL)
0.9
Race / Ethnicity
eGFR (mL/min/1.73m2) 92
White % 61
DM Duration (yrs)* 10
Black % 24
A1C (%)
8.3
Hispanic % 7
BMI (kg/m2) 32
* Median value 22

23. Systolic Pressures (mean + 95% CI)
Mean # Meds
Intensive:
Standard:
Average after 1st year: Standard vs Intensive, Delta = 14.2 23

24. Medications Prescribed (12 Month Visit)

25. Adverse Events Intensive N (%) Standard P Serious AE 77 (3.3) 30 (1.3)
<0.0001
Hypotension
17 (0.7)
1 (0.04)
Syncope
12 (0.5)
5 (0.2)
0.10
Bradycardia or Arrhythmia
3 (0.1)
0.02
Hyperkalemia
9 (0.4)
0.01
Renal Failure
0.12
eGFR ever <30 mL/min/1.73m2
99 (4.2)
52 (2.2)
<0.001
Any Dialysis or ESRD
59 (2.5)
58 (2.4)
0.93
Dizziness on Standing†
217 (44)
188 (40)
0.36
† Symptom experienced over past 30 days from HRQL sample of
N=969 participants assessed at 12, 36, and 48 months post-randomization

26. Primary & Secondary Outcomes
Intensive
Events (%/yr)
Standard
HR (95% CI) P
Primary
208 (1.87)
237 (2.09)
0.88 ( )
0.20
Total Mortality
150 (1.28)
144 (1.19)
1.07 ( )
0.55
Cardiovascular Deaths
60 (0.52)
58 (0.49)
1.06 ( )
0.74
Nonfatal MI
126 (1.13)
146 (1.28)
0.87 ( )
0.25
Nonfatal Stroke
34 (0.30)
55 (0.47)
0.63 ( )
0.03
Total Stroke
36 (0.32)
62 (0.53)
0.59 ( )
0.01
Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and unstable angina
(HR=0.95, p=0.40)

27. Nonfatal Stroke Total Stroke HR = 0.63 HR = 0.59 95% CI (0.41-0.96)
P=0.03
HR = 0.59
95% CI ( )
P=0.01

28. Clinical Trials of BP Lowering in Patients with Diabetes:
SBP Goals, Mean Achieved SBP, Outcomes

29. Conclusions
The ACCORD BP trial evaluated the effect of targeting a SBP goal of 120 mm Hg, compared to a goal of 140 mm Hg, in patients with type 2 diabetes at increased cardiovascular risk.
The results provide no conclusive evidence that the intensive BP control strategy reduces the rate of a composite of major CVD events in such patients.