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 SBP (mmHg) Age (years) SBP MenSBP 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 separately ii.SBP from 2 rounds of data collection iii.Treatment for hypertension included in addition to SBP iv.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 / cm 2 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  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/cm 2 per mm HG), 95% confidence intervals, p values and adjusted r 2 for predictors of LVMI in a sex-adjusted multivariable model containing both current SBP and SBP at age 53 Variable  coefficient (95% CI )p valuer2r2 SBP (current) 0.08 (0.002 to 0.16) SBP (age 53) 0.25(0.18 to 0.33)<0.001

Results – Effect of treatment on LVMI Regression coefficients (g/cm 2 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  coefficient (95% CI )p value Current Rx12.3(9.2 to 15.4)<0.001 Rx at age (5.9 to 14.1)<0.001 Rx at age (5.8 to 24.3)0.001 Rx at age (-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

Results – Rate of change of SBP from age 36y to 53y on LVMI Regression coefficients (g/cm 2 per mm HG/ year; g/cm 2 per mm HG), 95% confidence intervals, p values and adjusted r 2 for a sex-adjusted model with change in SBP (36-53y), SBP at 36y, current SBP and current LVMI Variable  coefficient (95% CI )p valuer2r2 Rate of change in SBP from 36 to 53y 18.4 (11.7 to 25.1) < SBP at 36y 0.2 (-0.0 to 0.4) 0.12 Current SBP 0.1 (0.0 to 0.2) 0.02 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 Number of people on antihypertensive treatment