Effect of adult life course blood pressure on cardiac structure in the MRC 1946 birth

cohort

British Hypertension Society 2011

Dr Arjun K Ghosh

MRC Clinical Career Development Fellow and Specialty Registrar in Cardiology, International Centre for Circulatory Health, Imperial College, London

MRC NSHD is the oldest British birth cohort study 5362 men and women born in one week in March 1946 >20 data collection time-points throughout life 1653 echocardiograms at most recent data collection

(age 60-64y) Life course approach to data analysis

Background

Life course approach

Hypothesis: exposures acting over the life course affect disease susceptibility

e.g. BP across the life course has an effect on subsequent left ventricular (LV) structure

The life course approach may offer better mechanistic understanding and allow earlier targeted interventions Mean SBP changes in 1946 cohort

110

115

120

125

130

135

140

145

30 50 70S

BP

(m

mH

g)

Age (years)

SBP Men SBP Women

To examine the effects of adult life course systolic blood pressure (SBP) on future LV structure (LV wall thickness and mass)

To determine if previous SBPs can add anything over and above current SBP as a predictor of future LV wall thickness and mass

To determine if rate of change in SBP or “cumulative burden” of SBP influences future LV structure

To investigate the effect of antihypertensive treatment over the life course on LV structure

Aim

Series of multivariable regression models fitted with cardiac outcome (all models adjusted for sex)

Sex by SBP interactions tested in order to investigate if associations differ in men and women

Order of modelling:i. SBP from each round fitted separatelyii. SBP from 2 rounds of data collectioniii. Treatment for hypertension included in addition to SBPiv. Examined whether change in SBP from 36y to current age or

“cumulative burden” of SBP [represented by Area Under the Curve (AUC) of SBP] predict current LV wall thickness and mass

Methods

Results – predictive value of previous SBP on LVMI

Regression coefficients (g/cm2 per mm HG), 95% confidence intervals and p values for 4 separate sex-adjusted models containing SBP at different ages

and current LV mass index (LVMI)

Variable b coefficient (95% CI ) p value

SBP (current) 0.20 (0.12 to 0.27) <0.001

SBP (age 53) 0.28 (0.21 to 0.35) <0.001

SBP (age 43) 0.13 (0.04 to 0.22) 0.007

SBP (age 36) 0.14 (0.04 to 0.24) 0.006

Results – predictive value of previous SBP over and above current SBP on LVMI

Regression coefficients (g/cm2 per mm HG), 95% confidence intervals, p values and adjusted r2 for predictors of LVMI in a sex-adjusted multivariable model

containing both current SBP and SBP at age 53

Variable b coefficient (95% CI ) p value r2

SBP (current) 0.08 (0.002 to 0.16) 0.0460.13

SBP (age 53) 0.25 (0.18 to 0.33) <0.001

Results – Effect of treatment on LVMI

Regression coefficients (g/cm2 treatment vs. no treatment), 95% confidence intervals and p values for 4 separate sex-adjusted models with treatment and

SBP at different ages and current LVMI

Variable b coefficient (95% CI ) p value

Current Rx 12.3 (9.2 to 15.4) <0.001Rx at age 53 10.0 (5.9 to 14.1) <0.001Rx at age 43 15.1 (5.8 to 24.3) 0.001Rx at age 36 - 0.6 (-14.7 to 13.6) 0.939

Rate of change vs. Area Under the Curve

AUC and slopes for two individuals – one with persistently elevated SBP, the other with gradually increasing SBP

36 43 53 63110115120125130135140145

Persistently elevated SBP Linear (Persistently elevated SBP) Gradually elevated SBP

Linear (Gradually elevated SBP)

Age (years)

SBP

(mm

Hg)

Results – Rate of change of SBP from age 36y to 53y on LVMI

Regression coefficients (g/cm2 per mm HG/ year; g/cm2 per mm HG) , 95% confidence intervals, p values and adjusted r2 for a sex-adjusted

model with change in SBP (36-53y), SBP at 36y , current SBP and current

LVMI

Variable b coefficient (95% CI ) p value r2

Rate of change in SBP from 36 to 53y

18.4 (11.7 to 25.1) <0.001

0.13

SBP at 36y 0.2 (-0.0 to

0.4) 0.12

Current SBP 0.1 (0.0 to

0.2) 0.02

36 43 53 63100

110

120

130

140

150

Age (years)SB

P (m

mHg

)

Two components in calculating the Area Under the Curve

SBP over the adult life course predicts future LV structure SBP at age 53 is a stronger predictor of LVMI than current SBP,

although both independently predict LVMI in a multivariable model

Rate of change in SBP from 36y to 53y may be an important determinant of future LV structure

Antihypertensive treatment from the age of 43 onwards is associated with elevated LVMI independent of SBP at the corresponding age, suggesting that treatment may fail to normalize LVMI

A chance to intervene missed?

Conclusions

My Supervisors, funders and mentor – Professor Alun Hughes, Dr Rebecca Hardy, Dr Darrel Francis, Professor Nishi Chaturvedi, Professor Di Kuh and Professor Jamil Mayet

Colleagues at MRC LHA

Colleagues at ICCH, Imperial College

Acknowledgements

Thank You

Mean BP 136/78 Mean BP in men 140/80, mean BP in women 133/76 Mean BP in those on antihypertensive treatment 139/79 Mean BP in those off antihypertensive treatment 135/77 Mean BMI 27.94, similar in men and women

BP and BMI characteristics

Age 36 – 51

Age 43 – 107

Age 53 – 438

Age 60-64 - 640

Number of people on antihypertensive treatment