Genetic and cardiovascular risk factors in relation to physical - - PowerPoint PPT Presentation

Genetic and cardiovascular risk factors in relation to physical limitation

Emerald G. Heiland, PhD candidate Aging Research Center, Karolinska Institutet, Stockholm, Sweden Emerald.heiland@ki.se

CONFLICT OF INTEREST DISCLOSURE

I have no potential conflict of interest to report

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APOE ε4 allele

Haan et al. Curr Cardiovasc Risk Rep 2010 Verghese et al. Lancet Neurol 2011; Bertram et

• al. Nat Genet 2007

APOE ε4 and physical function limitation in longitudinal studies- inconsistent results

Skoog et al. Front Aging Neurosci 2016 Alfred et al. AGE 2014 Melzer et al. Gerontology 2005 Verghese et al. Gerontology 2013 Walking speed decline Disability Walking speed Chair stand Grip strength Get up and go/walking speed Chair stand Balance Grip strength Walking speed Chair stand Balance Grip strength Walking speed decline Chair stand Walking speed decline in men

Welmer et al. PLoS ONE 2013

Cardiovascular risk factors (CRFs) and mobility limitations

1  2 1  2 0 .5 1 2 4 8

O d d s R a tio (9 5 % C I) N o n  4 c a rrie rs  4 C a rrie rs N u m b e r o f c a rd io v a s c u la r ris k fa c to rs

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APOE ɛ4 Incident limitation of three physical functions Cardiovascular risk factors

Aims

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Swedish National study on Aging and Care-Kungsholmen

Study Population

Three outcomes

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3363

803 missing or with baseline limitation

Analytical sample n=1401

952 with cardiovascular diseases

<5 seconds <0.8 m/s

Cannot stand without using arms 94 missing or with baseline limitation 45 missing or with baseline limitation 69 missing APOE

Exposure

APOE ε4 Behavioural CRFs: Physical inactivity, current smoking, heavy alcohol consumption Cardiometabolic CRFs: Obesity, hypertension, high total cholesterol, diabetes Covariates: Sex, cognitive function (MMSE) Statistical analysis: Cox proportional hazards regression, with age as time-scale

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B a la n c e lim ita tio n W a lk in g s p e e d lim ita tio n C h a ir s ta n d lim ita tio n 0 .5 1 2 4

H a z a rd R a tio s (9 5 % C I) 1 .1 4 1 .1 9 1 .5 7

APOE ε4 and incident physical function limitation (n=1401)

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Adjusted for sex, cognitive function, CRFs, and incident CVDs N=211 N=153 N=180

• No. Incident cases

Combined CRFs and APOE ε4 and the risk of chair stand limitation

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Adjusted for sex, cognitive function, and mutual CRFs

N /N Y /N N /Y Y /Y N /N Y /N N /Y Y /Y 0 .5 1 2 4 8

H a z a rd R a tio s (9 5 % C I) C R F s /  4 1 .3 5 1 .3 4 2 .5 6 1 .0 1 2 .5 3 1 .4 1 B e h a vio u ra l C R F s C a rd io m e ta b o lic C R F s

Behavioural CRFs and the risk of chair stand limitation

Adjusted for sex, cognitive function, and mutual CRFs

n o 4 4 n o 4 4 n o 4 4 0 .2 5 0 .5 1 2 4 8

H a z a rd R a tio s (9 5 % C I) P h y s ic a l in a c tiv ity C u rre n t s m o ke r H e a vy a lco h o l c o n su m p tio n 2 .4 4 1 .4 8 1 .8 8 1 .0 7 1 .2 9 0 .8 5

• APOE ɛ4 is associated with a greater risk of

chair stand limitation among adults ≥60 years

• Together behavioural CRFs and APOE ε4 may

heighten the risk of reduced muscle strength

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Conclusions

Thank You!

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SNAC-K participants and data collectors Supervisors: Chengxuan Qiu, Anna-Karin Welmer, and Laura Fratiglioni Co-authors: Rui Wang, Debora Rizzuto Swedish Research Council Swedish Research Council for Health, Working Life and Welfare KID-Funding Eva & Oscar Ahréns Stiftelse Gun & Bertil Stohnes Stiftelse Stiftelsen Ragnhild och Einar Lundströms Minne Emerald.heiland@ki.se

Flowchart

3 year follow-up (2004-2007) 6 year follow-up (2007-2010) 9 year follow-up (2010-2013)

220 ≥78 years 1019 195 159 130 19 refused 1 no contact 16 died 7 refused 1 no contact 17 died 17 refused 5 no contact 11 died Analytical sample 1401 participants 1181<78 years 77 refused 35 no contact 50 died 15 refused 3 no contact 7 died 161-only 72 yrs 3363 participants aged ≥60 years 952 with CVD at baseline 941 with limitation or missing in balance, walking speed, or chair stand at baseline 69 missing APOE gene

Baseline survey (2001-2004)

Physical Function

Abellan van Kan et al. J Nutr Health Aging 2009 Guralnik et al. J Gerontol A 2000 Heiland et al. Age & Ageing 2016 Minneci J Am Geriatr Soc 2015 Perera J Gerontol A 2015 Den Ouden et al. Exp Gerontol 2013 Newman et al. J Gerontol A 2003 Kattainen et al. J Clin Epid 2004

Behavioural CRFs Physical inactivity (never engaged in PA, engaged <2-3x/mo., or light and/or mod/intense 2-3x/mo.) vs. health-enhancing (light several times per wk) or fitness enhancing (mod/intense several times per wk) : questionnaire of activity in last 12 months (Rydwik Eur J Public Heal 2012) Heavy alcohol consumption vs. no occasional, light to moderate: based on a typical drinking day; >14 drinks per week for men or >7 for per week for women. One standard drink = 150ml (Breslow Am J Clin Nutr 2013) Current smoking vs. never or formerly: self-report Cardiometabolic CRFs Hypertension: ≥140/90mmHg or current use of anti-hypertensive agents(ATC codes; C02, C03, and C07-C09). (Perk Int J Beh Med 2012) Diabetes: according to self-reported history, records from the National Inpatient Registry, the use of hypoglycemic agents (ATC A10), or ≥6.5% glycated hemoglobin level. (Diabetes Care 2014) Total high cholesterol: ≥6.22mmol/L (non-fasting). (Cowie Diabetes Care 2006; Circulation 2002) Obesity: ≥30kg/m2. (Obesity Research 1998)

CRFS definitions

• Ascertainment of cardiovascular disease.

Coronary heart disease, atrial fibrillation, heart failure, and cerebrovascular diseases were defined based on clinical examination, electrocardiogram, drug data, and Inpatient Register information (Calderón-Larrañaga J Gerontol A Biol Sci Med Sci 2016).

Cardiovascular disease

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APOE Gene

• Associated with brain disease (refs) – that increase the

risk of disability

• ε4 allele known to increase risk of dementia
• Associated with CVD (Haan et al. Curr Cardiovasc Risk

Rep 2010)

• Little known and discordant results on association with

physical limitation

• More longitudinal studies needed

APOE ε4 and physical function (PF) limitation in longitudinal studies- inconsistent results

PF studied PF associated with APOE Skoog et al. Front Aging Neurosci 2016 N=622 4 years follow-up

Grip strength Regular gait speed Chair stand balance Grip strength

Alfred et al. AGE 2014 N=23 916 Years follow-up vary

Grip strength Get up and go/walking speed Timed chair rise Balance ≥3s Cross-sectionally: chair stand Longitudinally: walking speed decline

Melzer et al. Gerontology 2005 N=1262 6 years follow-up

Gait speed 5 chair stands 5 chair stands

Verghese et al. Gerontology 2013 N=627 3 years follow-up

Gait decline Disability Only associated with gait speed decline in men

Buchman Alzheimer Dis Assoc Disord 2009 N=876 10 years

Time and number of steps to walk 8ft and turn; time to stand

• n each leg an then on their toes

for 10secs; number of steps off line when walking; number of pegs that could be placed (Purdue pegboard) in 30 secs Motor decline, mainly due to muscle strength

• Twin studies
• Suggested that there is a high heredity component in

connection with chair stand and walking speed, but not balance (Carmelli et al. J Gerontol 2000)

• Genetic factors accounted for 46% of the variance in

repeated chair stands (Carmelli et al. J Gerontol 2000)

• Offspring of parents with genes for good physical

funcion are more likely to have better results on this association

Is physical function heritable?

Thank You!

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SNAC-K participants and data collectors Supervisors: Chengxuan Qiu, Anna-Karin Welmer, and Laura Fratiglioni Co-authors: Rui Wang, Debora Rizzuto Swedish Research Council Swedish Research Council for Health, Working Life and Welfare KID-Funding Eva & Oscar Ahréns Stiftelse Gun & Bertil Stohnes Stiftelse Stiftelsen Ragnhild och Einar Lundströms Minne Emerald.heiland@ki.se