1. Ageing with ideal cardiovascular risk factors
In 421,000 participants from CPRD and UK Biobank
J Atkins, J Delgado, K Bowman, D. Melzer
University of Exeter
19/09/2018

2. Introduction
Ageing is very variable, and its unclear how much of frailty in later life is preventable
CVD risk factors claimed by some to not be important in late life –
Weight
Blood pressures control
Cholesterol level
*Lloyd-Jones et al, Circulation, 2010

3. Introduction
In previous work our group sought to clarify specific cases of reported paradoxical associations in late life:
The obesity paradox (being overweight is beneficial in later life)*
Blood pressure control in later life (optimal target for older individuals) ±
The work I am presenting here, focusses
How cardiovascular risk affect ageing in `typical’ older adults
All-cause mortality and cardiovascular events
Ageing phenotypes and frailty
Cardiovascular risk score based on AHA Simple 7* risks
* Bowman et al. J Gerontol A Biol Sci Med Sci, 2016, ±J Delgado et al. J Am Geriatr Soc, 2016

4. Combined Risk Score 60–69 yr. 35.5% 6.5 % 62.1% 67.5 % 2.4% 26.0 %
6 CVD risk factors summed into a total risk score (range 0-12)
Blood pressure, total cholesterol, fasting blood glucose, BMI, Physical activity, Smoking*, & Diet
HIGH
INTER-MEDIATE
IDEAL
60–69 yr.
Total number
Scores = 0-5
35.5%
6.5 %
Scores = 6-9
62.1%
67.5 %
Scores = 10-12
2.4%
26.0 %
239,591
CPRD
UKbiobank
181,820
*Lloyd-Jones et al, Circulation, 2010

5. CVD - outcomes by risk score
High vs. Ideal - HR death and SHR for incidence of selected outcomes
Follow-up <10 years
Excluding prior conditions & adjusted for Age, Gender, IMD, year of study entry
Death
Coronary heart disease
Stroke
Heart failure
Cancer
Anaemia
Depression
Dementia

6. UKB - Ageing phenotypes
Poor vs. Ideal; vs. intermediate - for selected outcomes
Outcomes measured a baseline & adjusted for age, gender and TDI
Frailty (fried phenotype)
Poor/fair self-perceived health
Long-standing illness, disability
Low FEV (lowest 20% sex specific)
Chronic pain
Poor cognitive function (FI lowest 20%)
Low grip strength (lowest 20%)
Urinary incontinence

7. CPRD – Frailty progression
Proportion of new cases of moderate/severe frailty –adapted Rockwood Frailty Index
Follow-up of 9 years
If all individuals had ideal combined risk score
PAF
CI (95%)
0.76
0.65 : 0.83
High
Intermediate
Ideal
Survival analysis Ideal (sHR=0.15 CI ) and intermediate CRS (sHR=0.38 CI ) were associated with much lower incidence of frailty (figure 2).

8. Conclusions
Controlling CVD risk factors including blood pressure and cholesterol level reduced mortality and CVD.
In line with RCT evidence (SPRINT* and HOPE-3 ±)
An optimal “combined” score of risk factors is strongly associated with healthy aging:
Frailty – 79% reduction in incidence of severe frailty,
Chronic pain – 40% lower prevalence etc
Only 2.4% of 60 to 69 year olds have ideal CVD risks:
dose response relationships – so even small changes in population risk profile could matter for ageing well
Older people with optimal lifestyle health risks age better, especially in terms of frailty/pain/strength/cognition.
- Frailty: 60% decreased odds in those with ideal vs poor health risks. (Largest effect seen - measure of lifestyle).
For CPRD Frailty (RFI) 4,532 HR <0.001 HR <0.001
Chronic pain (new): 40% decreased odds in those with ideal vs poor health risks.
Supports multiple protective factor model of ageing which influences disease and frailty/pain.
* Williamson J. et al., JAMA, 2016; ± Yusuf S. et al., N Engl J Med, 2016

9. Conclusions
We already have tools for radical improvement in human ageing… …without hypothesised cures for intrinsic biological ageing.
*Low responses – healthy cohort. However, this is only likely to have underestimated effect sizes. Bigger effects seen in less healthy.
Need longer term data.
Also, why does the WHO report have so little on controlling CVD risks?

10. Thank you
Epidemiology and Public Health, University of Exeter Medical School
Janice Atkins
João Delgado
Kirsty Bowman
David Melzer

11. Clinical practice research datalink NHS funded database
Practice + Patient
Primary Care
≈ 2 million records
Resources
Hospital Episodes
Diagnosis
Procedures
Symptoms
Diagnoses
Immunisations
Lifestyle Factors
Referrals
Prescriptions
Test Results
Office of National Statistics
Mortality

12. UK Biobank Baseline: 2006-2010 - 500,000 participants 40-69 years
- 22 assessment centres
- 215,103 aged 60 to 69,
Follow-up:
- National Death registrations
- Hospital Episode Statistics (HES) = incident diagnoses