Clinical Significance of an Exaggerated Blood Pressure Response During Exercise

ANDREAS PITTARAS MD

Patient A Patient B

Age 67 58

Rest BP 120/80 120/78

BP @ 5 METs 160/80 220/90

Peak BP 190/80 230/100

QUESTIONS

• The Clinical Significance?

• What to do about it?

Definition

• Peak Exercise SBP >210 mm Hg for men and 190 mm Hg for women respectively (Framingham)

• SBP >200 mm Hg at Exercise Workload of about 6-7 METs

Exaggerated BP Response toExercise and Associations

• Future Development of HTN

• Cardiovascular Mortality and Cardiovascular events

• Left Ventricular Hypertrophy

Clinical Significance

False-positive results were twice

as likely in patients with hypertensive response to

exercise echocardiography

(22% vs 12%).

Jong-Won Ha, et al. JACC 2002:112:161-66

Exaggerated BP and Future Development of

Hypertension

New-onset of HTN and Exercise BP in Men (n=1026) The Framingham Heart Study

1.36

2.17

1

4.16

0

2

4

Women Men

Odds Ratio

DBP

SBP

*

*

Singh JP, et al. Circulation 1999;99:1831-36

Exaggerated BP Response to Exercise and Risk for Developing HTN (n=1,033)

1 1

3.7

2.89

6.62

4.91

0

2

4

6

8

Multiple Adjusted Age-Adjusted

Miyai, et al. Hypertension 2002;39:761-6

DBP

SBP

4.7 yrs F/U

Relative Risk

Exaggerated BP Response to Exercise and Risk for Developing HTN

3.82

3.17

1.08 1.05

0

1

2

3

4

Exag-BP Resting HTN BMI Age

Miyai, et al. Hypertension 2002;39:761-6Relative Risk

Exaggerated Exercise BP and Future HTN (Conclusion)

• Overall, an exaggerated BP response to exercise is likely to lead to future HTN

• Confounding factors such as age, gender, and physical fitness have not always been considered

• Pre-hypertension ?

Patients with Pre-hypertension are at twice the risk to develop

hypertension compared to those with lower BP values.

Vasan RS, et al. The Framingham Study. JAMA 2002;287:1003-1010

Exaggerated BP and CV Events and CV Mortality

Exercise BP and CV Mortality in Middle-aged Men (n=1999)

5.6 6

8.1

16.1

0

9

18

%

<140 / <200 mm Hg

>140 / >200 mm Hg

<140 / >200 mm Hg

>140 / <200 mm Hg

Mundal et al. Hypertension 1994;24:56-62

* RR=2.0

NS

F/U: 16 yrs

Exercise BP and Risk of Developing MI in Middle-aged Men (n=1999)

9.5

18.8

11.4

15.7

5

10

15

20

%

*

<140 / <200 mm Hg

>140 / <200 mm Hg

>140 / >200 mm Hg

<140 / >200 mm Hg

Mundal et al. 1996; Hypertension;27:324-29

Conclusion

SBP >200 mm Hg at exercise intensity of about 6 METs is a stronger predictor of CV and MI morbidity and mortality than resting BP In pts with resting HTN.

Mundal R. et al., Hypertension 1996;27(1):324-29

Exaggerated BP Response and

Left Ventricular

Hypertrophy

Resting BP is weakly related to LVH (r=0.26) and can only partially

explain its development

and progression.

Exaggerated BP & LVH in Normotensive Men

An exaggerated blood pressure (SBP >210) at peak exercise is associated with left ventricular hypertrophy (LVH). The association is much

stronger than that between resting BP and LVH.

Gottdiener JS., et al. Annals of Internal Medicine 1990; 112:116-66

Peak Exercise SBP and LV MASS

224 222

180

155

143

124

110

140

170

200

230

Peak SBP LVMI

HTN with SBP >210 mm Hg

<210 mm Hg

Polonia J, et al. Eur Heart Journal 1992; 13(A):30-36g/m2

>210 mm Hg

Peak Exercise BP and LV MASS

220

176

124

103

80

110

140

170

200

230

Peak SBP LVMI

<210 mm Hg

Molina L, et al. Am J Cardiol 1999; 84:890-93

>210 mm Hg

Peak Exercise BP (SBP>210 mm Hg) and LVH in Men & Women

106

111

74

80

60

80

100

120

Men Women

<210 mm Hg

>210 mm Hg

Lauer et al. Annals Intern Med 1992;116;203-10g/m2

Conclusion

The relationship between Peak exercise BP and LVM is

confounded by a number of baseline variables so that its

biological significance must be questioned.

Lauer et al. Annals Intern Med 1992;116;203-10

Peak vs Sub-maximal Exercise BP

Peak Exercise BP

–Relatively difficult to assess

–Impractical

–Based on a relative workload

Exer. BP (5-7 METs)

–Easier to assess

–Practical (reflects daily activities)

–Wider clinical application

–Based on absolute workloads

Exercise SBP and Fitness in Normotensive Men (n=1,025)

161

149

140

173

166

153

178

182179

125

145

165

185

SBP @ 5 METs SBP@ 7-METs Peak Exercise

*

* p<0.01

mm Hg Low-Fit Moderate High-Fit

*

*

Patients with Pre-hypertension (SBP 120-139 mm Hg or DBP 80-89 mm Hg), are at twice the risk to develop hypertension compared to those with lower BP values.

Vasan RS, et al. The Framingham Study. JAMA 2002;287:1003-1010

LVMI Predictors for Pre-HTNsiveMen (Multiple Regression)

M (n=269) W (n=243)

R2 R2

• SBP @ 7 METs 0.62 0.50

• Age 0.64 0.51

• T-Time 0.65 0.53

LVMI & Exercise SBP Association in Pre-Hypertensive Women

Kokkinos P, Pittaras A et al. Circulation 2004

SBP at 7 METs

240220200180160140120

LV

MI

(kg

/m2

)

200

180

160

140

120

100

80

60SBP>169 mm Hg

LVMI & Exercise SBP Association in Pre-Hypertensive Men Kokkinos P., Pittaras A et al. Circulation 2004

SBP at 7 METs

220200180160140120

LV

MI

(kg

/m2

)

200

180

160

140

120

100

80

60SBP>164 mm Hg

LVMI & Exercise SBP in Pre-hypertensive Men and Women

133

96

120

92

75

85

95

105

115

125

135

Women Men

*

* p<0.01

Normal

EX-HTN

*

Kokkinos P., Pittaras A et al. Circulation 2004g/m2

Prevalence of LVH in Pre-HTNMen % OR CI p-value

–EX-HTN (+): 59 30.2 13.8-66.2 0.00–EX-HTN (-) : 4.5

–RR= 5.9 times higher likelihood of LVH/10 mm

Hg Increase in SBP@ 6 min. of exercise

Women–EX-HTN (+): 86 21.6 12.3-38.2 0.00–EX-HTN (-) : 22 –RR= 2.9 times higher likelihood of LVH/10 mm

Hg increase in SBP@ 6 min. of exercise

Conclusions• Systolic BP at about 6-7 METs is the strongest predictor of LV mass in Pre-hypertensive men and women.

• The threshold for LVH is SBP >164 mm Hg for men and >169mm Hg for Women.

• The likelihood of having LVH increases by 6-fold in men and 3-fold in women for every 10 mm Hg increase in SBP above these thresholds.

What to Do for Patients with Exaggerated BP Response

to Exercise ?

• Antihypertensive Agents

• Exercise Training

Exercise BP and Antihypertensive Meds (n=1,977)

151

167164

182 175

192

145

170

195

SBP@ 5 MET SBP@ 7 METS SBP @ Peak

*

** p<0.01BB-Based

Others

*

*

mm Hg

Exercise BP and Antihypertensive Agents (n=1,977)

152

166164

166164

180182

181

140

155

170

185

SBP@ 5 MET SBP@ 7 METS

* p<0.01

BB-Based

ACE

CCB

Diuretics

mm Hg

Clinical Significance

Beta-blockade may be a prudent approach to protect against excessive and repetitive elevations in BP likely to occur during vigorous activities such snow-shoveling basketball, tennis, etc., that require repetitive burst of effort to maximal or near maximal levels.

What to Do for Patients with Exaggerated BP Response

to Exercise ?

• Antihypertensive Meds

• Exercise Training

Exercise Indices for Fit and Unfit Women

Normotensive Fit (n= 557) Unfit (n=463)

SBP- 6 min 145±18 156±20*

HR- 6 min 136±15 152±17*

Hypertensive Fit (n= 99) Unfit (n=186)

SBP- 6 min 172±21 184±21*

HR- 6 min 141±15 156±15*

Kokkinos P. Pittaras A et al, J Cardiopulmonary Rehab 2002;22:178-183

* p =0.000

Exercise BP, Fitness & LVMI in Men

184

175

165

135

125

117

106

126

146

166

186

SBP @ 7 METs LVMI

*

*

* p<0.01

Pittaras A, et al. Circulation 2003

Low-Fit

Moderate

High-Fit

Exercise BP, Fitness & LVMI in Women

187

177

167

140

127

117

100

130

160

190

EX-BP LVMI

*

*

* p<0.01

Pittaras A, et al. Circulation 2003

Low-Fit

Moderate

High-Fit

SBP Following Aerobic Training

138131

198

171

219

187

219

199

120

140

160

180

200

220

Rest 6-Min 9-Min Peak

*

*

*

*p<0.01

*

Kokkinos P. et al, Am J Cardiol. 1997

mm Hg

Wall Thickness at Baseline and 16 wks

12

13

14

15

PW IVS

mm

Kokkinos, Pittaras A et al. New Engl J Med 1995;333:1462-7

*

*

* p<0.05

LVMI at Baseline and 16 Wks of Exercise

163

143

135

150

165

Kokkinos, Pittaras A et al. New Engl J Med 1995;333:1462-7

*

* p<0.05

Baseline 16 weeks

g/m2

Antihypertensive Agents and Exercise

Exercise SBP and Fitness in Hypertensive Men on B-Blockers (n=453)

156

146

136

171

163

155

173 174

170

120

140

160

180

SBP @ 5 METs SBP@ 7-METs Peak Exercise

*

* p<0.01

mm Hg Low-Fit Moderate High-Fit

*

*

Exercise SBP and Fitness in Hypertensive Men on Meds (n=455)

179

163

155

193

181

170

196193 192

140

160

180

200

SBP @ 5 METs SBP@ 7-METs Peak Exercise

*

* p<0.01

mm Hg Low-Fit Moderate High-Fit

*

*

Does exercise BP at 5-7 METs reflect daytime Ambulatory BP?

Exercise BP & ABP in Fit & Unfit Men

151

159

126

144147

111

100

115

130

145

160

Unfit Fit

EX-BP

ABPM

LVMI

LVMI

EX-BP

ABPM

Exercise BP & ABP in Fit & Unfit Women

153

164

133

143148

113

90

105

120

135

150

165

Unfit Fit

EX-BP

ABPM

LVMI

LVMI

EX-BPABPM

Summary and Conlusions• Fit individuals have Lower:

• BP at intensities of 5-7 METs• Lower ABPM • Lower LVMI Than Unfit.

• Physical activity lowers the daily hymodymanic load, leading to lower LV Mass.

Mitigates the hemodynamic load

During Daily Activities

Prevents or Attenuates Increases

in LV Mass

How Much Physical Activity?• Some is Better than None!

• Choose an activity you enjoy

• Start Low & Progress Slowly

• Start as low as 10 min/week

• Split duration (AM/PM) if needed

• Increase duration by 1-2 min/wk

• Goal: 100-200 minutes/week

• Be Consistent (2-6 times/week)

How Much Physical Activity ?

Think F.I.T

F- Frequency: 2-6 days/Wk

I – Intensity : 60-80% of HRR

T- Time : 100-200 min/week

• The daily hemodynamic load is likely the impetus for the

development and progression of LVH. • SBP at 5-7 METs of exercise reflects the hemodynamic load during daily activities.

Therefore, attenuating

an abnormal rise in BP during daily physical

exertion may prevent the development and/or

maintenance of LVH.

Conclusion 1

High fit Women had:

• Lower LVMI • BP @ 6 min of Exercise

• The metabolic demand of about 6-7 METs at 6 min of exercise (Bruce protocol) is equivalent to that of most daily activities. Thus, the 6-minute exercise BP may reflect the hemodynamic load during daily activities.

• Furthermore, the maintenance and progression of LVH may be mediated by this daily hemodynamic load. Thus, attenuating an abnormal rise in BP during daily physical exertion may prevent the development and/or maintenance of LVH.

Correlation of 6-minute Exercise SBP, LVMI and Daytime ABP in Men

SBP@6-min ABPM

LVMI

r=0.73

r=0.81 r=0.68

Correlation of 6-minute Exercise SBP, LVMI and Daytime ABP in Women

SBP@6-min ABPM

LVMI

r=0.79

r=0.71 r=0.67

Peak Exercise DBP Before and After Exercise Training in Women

97

9394

89

80

90

100

Baseline 4 wks 8 wks 12 wks

Seals et al, Am J Cardiol ‘97mm Hg

P<0.05

Peak Exercise SBP Before and After Exercise Training in Women

183

176

171

162

150

170

190

Baseline 4 wks 8 wks 12 wks

Seals et al, Am J Cardiol ‘97mm Hg

P<0.05

Exercise RPP at Pre & Post Training

15

20

25

30

35

6 min 9 min Peak

RP

P *

100

0

*

*

*

*p<0.05

Kokkinos P. et al, Am J Cardiol. 1997

Exaggerated BP & False-Positive Exercise Test Results

Jong-Won Ha, et al. JACC 2002:112:161-66

• 132 pts with Peak Exercise SBP>220 mm Hg for Men; > 190 mm Hg for Women

• 108 had positive exercise Echo finding

• 24/108 (22%) had no significant CAD

• 416 pts with Normal Exercise BP

• 320 had Positive Exercise Echo Findings

• 39/320 (12%) had no significant CAD

Exercise Response for Pts on Beta-Blockers vs Other Antihypertensive Meds

Variables Others (n=1254) BB (n=561) Δ

SBP @ 3 min 167±27 151±26 16SBP @ 6 min 182±27 164±25 18 Peak SBP 192±28 175±30 17HR @ 3 min 119±17 106±17 13HR @ 6 Min 133±16 119±18 14Peak HR 148±17 31±21 17Ex. Time (sec) 412±166 419±160 7

P<0.001

BP Response to HR During Exercise Test and Risk of Future Hypertension

Miyai N, et al. Hypertension 2002;39761-66

• N=1033 Men, No HTN, DM or CVD• Cycle Ergometer; Automated BP

monitoring device.• Age: 42.9 ±8.5 yrs; range: 20-59 yrs• 726 pts with complete data; • 4.7 yrs F/U

Exercise BP Predicts CV Mortality in Middle-aged Men

Mundal et al. 1994; Hypertension;24:56-62

• N=1999 healthy men

• F/U: 16 yrs

• Exercise BP at 600 kg-m/min (~100 watts; approximately 6 METs)

Peak Exercise SBP and LV MASS

152

174

190

124

143

155

100

120

140

160

180

200

BP @ 3 min LVMI

HTN with SBP >210 mm Hg

<210 mm Hg

Polonia J, et al. Eur Heart Journal 1992; 13(A):30-36g/m2

>210 mm Hg

• SBP at sub-maximal exercise reflects the daily hemodynamic load.

• Therefore, it may be a stronger predictor of HTN and LVH.

• Sub-maximal exercise BP may also have a wider clinical application than maximal exercise BP.

• Left ventricular hypertrophy (LVH) is a powerful and independent predictor of cardiovascular events in patients with and without obstructive coronary disease.

• The risk for CV morbid events, including sudden cardiac death, increases-three fold in patients with LVH.

Levy D., et al. N Engl J Med 1990;332:1561-66

Ghali JK et al., 1992; Ann Intern Med 1992;117:831-36

Koren MJ et al., 1991; Ann Intern Med 1991;114:345-52

Casale PN, et al., Ann Intern Med 1986;105:173-78

Clinical Characteristics

Men Women

N 269 243 Age 49±10 54±10 RHR 78 ± 8 82 ±14RSBP 129 ±6 132 ±7RDBP 76±7 79 ±8 BMI 27±2.6 27±2.4

* p =0.008

Exercise SBP and Fitness in Hypertensive Men (n=908)

151

171

164

185173

195

130

150

170

190

SBP @ 5 METs SBP@ 7-METs Peak Exercise

*

mm Hg B-Blockers Other Meds

LVMI in Normotensive and Hypertensive Women

143

128

117

110

105

99

85

110

135

HTN (+) HTN (-)

*

*

* p<0.01

Kokkinos , Pittaras A et al. Circulation ‘98

g/m2

Low-Fit

Moderate

High-Fit

Exercise BP, Fitness & LVMI in Men

184

152

135

165

144

117

100

130

160

190

Low-Fit High-Fit

*

*

* p<0.01

Pittaras A, et al. Circulation 2003

EX-BP

ABPM

LVMI

SBP at 7 METs and LVMI in Fit & Unfit Normotensive Women

160

126

148

103

90

115

140

165

Low-Fit High-Fit

*

*

* p<0.02

Kokkinos P. Pittaras A et al. JACC ‘99

SBP LVMI LVMISBP

*

SBP at 7 METs and LVMI in Fit & Unfit Hypertensive Women

189

172

143

117

100

130

160

190

SBP LVMI

* * p<0.02

Kokkinos P. Pittaras A et al. JACC ‘99

Low-Fit High-Fit

*

Low-Fit High-Fit

Exaggerated BP & LVH in Normotensive Men

• Normotensive Men (N=39) • Age: 44.6±8.5• LVH (LVMI >134 g/m2 ) found in

63% (14/22) of those with Peak Exercise SBP >210 mm Hg.

Gottdiener J. et al. Annals Intern Med 1990:112:161-66

Correlations (r) of Sub-maximal Exercise SBP and ABP (n=892)

5-MET 7-MET r r

Daytime 0.71 0.78

Nighttime 0.69 0.77

24-hours 0.70 0.77

LVMI & Exercise SBP @ 7-METs in Pre-Hypertensive Women

187

157

133

96

85

110

135

160

185

SBP LVMI

* p<0.01

Normal BP

Ex-HTN

*

*

LVMI & Exercise SBP @ 7 METs in Pre-Hypertensive Men

80

105

130

155

180

SBP LVMI

* p<0.01 Normal BPEx-HTN

*

*