1. Should SPRINT change our practice?
CRT 2017, Washington, DC, USA
Should SPRINT
change our practice?
Thomas F. Lüscher, FESC, FRCP
Professor and Chairman Cardiology University Heart Center and
Director of Molecular Cardiology, University of Zürich, Switzerland

2. Disclosure Statement of Financial Interest
I have no disclosures for this talk

3. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

4. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

6. FDR‘s Bood Pressure Chart 1935 - 1945

7. St. Louis Post-Dispatch April 13, 1945

8. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

9. Stroke, Age and Blood Pressure
Systolic Blood Pressure
Diastolic Blood Pressure
Age at risk (years)
Age at risk (years)
256
128 64 32 16 8 4 2 1
256
128 64 32 16 8 4 2 1
80– %
80– %
70– %
70– %
60– %
60– %
50– %
Stroke mortality (floating absolute risk and 95% CI)
50– %
It has long been known that increased blood pressure is a risk factor for cerebrovascular and cardiovascular (CV) mortality (Stamler J et al. Arch Intern Med 1993). This association is illustrated by the results of the Prospective Studies Collaboration meta-analysis (Lewington S et al. Lancet 2002).
This large meta-analysis examined the records of one million adults who, at entry into one of 61 prospective observational studies, did not have pre-existing vascular disease.
This slide shows the stroke mortality rate in each decade of age versus usual blood pressure at the start of that decade. The data demonstrate that there is a strong and direct relationship between increased blood pressure and stroke mortality at all ages. This relationship did not have a threshold for a systolic blood pressure (SBP) above 115mmHg or a diastolic blood pressure (DBP) above 75mmHg at any age.
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–13.
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993;153:598–615.
Usual systolic blood pressure (mmHg)
Usual diastolic blood pressure (mmHg)
Lewington S, et al. Lancet 2002

10. Blood Pressure, Stroke and CAD
Hirnschlagsterblichkeit
(n=1233)
KHK Sterblichkeit
(n=11,149) 32 16 16 8
Relatives Risiko für
tödlichen Hirnschlag 8 4
Relatives Risiko für KHK Mortalität 4 2 2 1
Key Message: The strong positive relationship of SBP with the risks of stroke and CHD suggests that reduction of SBP has the potential to prevent stroke and CHD in both hypertensive and nonhypertensive patients.
While much of the original research on the association between BP and CHD focused on DBP, more recent evidence shows that SBP is an even more powerful predictor of disease risk.1 The strong positive relationship of SBP with the risks of stroke and CHD suggests that reduction of SBP has the potential to prevent stroke and CHD in both hypertensive and nonhypertensive patients.
The relative risks of death from stroke and CHD among men screened for the Multiple Risk Factor Intervention Trial (MRFIT) are shown.1 The relative risk of death from stroke was about 7 times greater in men with baseline SBP 151 mm Hg than in men with baseline SBP <112 mm Hg.1 Similarly, the relative risk of death from CHD for those with the higher SBP was about 4 times greater than for those with the lower SBP.
The risks of stroke and CHD continue to decline as BP is lowered. The absence of any lower BP limit (SBP <120 mm Hg) suggests that larger reductions in BP are likely to produce greater reductions in risk.
Reference
1. Neaton JD, Kuller L, Stamler J, et al. Impact of systolic and diastolic blood pressure on
cardiovascular mortality. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology,
Diagnosis, and Management. 2 ed. New York: Raven Press, 1995:
<120
125
135
148
168
120
125
135
148
168
Approximativer mittlerer systolischer BD (mm Hg)
Multiple Risk Factor Intervention Trial (MRFIT); n=347,978 men
Neaton et al. In: Laragh et al (eds). Hypertension: Pathophysiology, Diagnosis,
and Management. 2 ed. NY: Raven, 1995:127

11. Risk Factors and CV Events:
Life Time Risk
Berry et al. NEJM: 2012;366:321

12. Effect of Long-Term Antihypertensive Treatment
on Mortality: The Framingham-Study
Männer
Frauen
Frauen +
Männer 50
-23% 40
For optimal blood pressure control 2-3 antihypertensive drugs are required
-24% 30
-25%
Mortalitä (% über 10 Jahre) 20
-53%
-54% 10
-55%
Mortality
Total
Herz- Kreislauf
Total
Herz- Kreislauf
Total
Herz- Kreislauf
Ohne Behandlung
Mit Behandlung
Circulation 1996

13. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

14. What is a normal blood pressure?
Yanomani Indians
Yanomani Indios: 95/61 mmHg

15. What is a normal blood pressure?
Kuna Indians

17. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

20. Blood pressure lowering and clinical events
Ettehad et al. Lancet 2016

21. Should SPRINT change our practice?
Blood pressure, brain and Heart
Is the relation between BP and events linear?
What is a normal BP?
Is there a BP that is too low?
How low should BP ideally be?

23. Blood pressure lowering and clinical events
The SPRINT Research Group. NEJM 2015

24. Blood pressure lowering and clinical events
The SPRINT Research Group. NEJM 2015

26. Blood Pressure and Clinical Events Baseline Blood Pressure Subgroups of HOPE-3
Primary Outcomes: death, MI, stroke plus resuscitated SCD, CHF, revascularization

27. Blood Pressure and Clinical Events SPRINT versus HOPE-3
9361 hypertensives
Increased CV risk, no diabe-tes
Unattended BP measure-ment
Baseline sBP mmHg
sBP difference 14.8 mmHg
Final sBP mmHg
Event rate 1.65%/year ve. 2.19%/year (5.94% vs. 7.88%)
Follow-up 3.6 years
12‘705 hypertensives
No CV disease, intermedi-ate CV risk
Standard BP measure-ment
Baseline sBP mmHg
sBP difference 10.0 mmHg
Final sBP mmHg
Events 260 (4.1%) vs 279 (4.4%)
Follow-up 5.6 years

28. Blood Pressure Targets in Hypertensive Patients
BP and MACE are linearly related
In healthy individuals normal or optimal BP is 100/70mmHg
There might be a J-curve in patients with a individual sweet spot
sBP lowering beyond 140mmHg is protec-tive in those with higher base-line BP
Hypotension and renal dysfunction must be watched when BP is lowered to mmHg (this ma ba an opportunity for RNA)
Guidelines have to rethink and individua-lize sBP target levels