physical comorbidity with bipolar disorder

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Presentation from the International Congress of the Royal College of Psychiatrists 24-27 June 2014, London

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Physical comorbidity with bipolar disorder: lessons from UK data

Daniel Smith

Symposium 33: ‘Big data’ and bipolar disorder in the UK

“A failure of social policy and health promotion, illness prevention and care provision.”

Life expectancy at birth of people with mental disorders in the period of 2007–09 (N = 31,719).

Chang C-K, Hayes RD, Perera G, Broadbent MTM, et al. (2011) Life Expectancy at Birth for People with Serious Mental Illness and Other Major

Disorders from a Secondary Mental Health Care Case Register in London. PLoS ONE 6(5): e19590. doi:10.1371/journal.pone.0019590

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019590

UK data:

• Bipolar Disorder Research Network (n=8,000)

• Scottish Primary Care data (n=1.8 million)

• UK Biobank (n=0.5 million)

• Glasgow Psychosis cohort (n=7,500)

Cardiometabolic disease in BDRN cohort:

0

5

10

15

20

25

Diabetes Hypertension High

cholesterol

Coronary heart

disease

Stroke

Bipolar disorder

Controls

%

Forty et al, in submission

The analysis of ‘SPICE data’ was conducted as part of the Living Well

with Multimorbidity Programme (CSO Grant ARPG/07/1) with

Professor SW Mercer (Principal Investigator) and Professor Bruce

Guthrie (epidemiology lead).

Multimorbidity and major mental illness in Scotland:

– Data from 314 general practices in Scotland (1.8 million people)

– Schizophrenia and related psychoses and bipolar disorder identified (n=12,504)

– 32 physical health conditions also identified

– Multimorbidity described by age, gender and socioeconomic deprivation

– Some prescribing information

Physical health comorbidities assessed:

Coronary heart

disease

Parkinson’s disease Peripheral vascular

disease

Viral hepatitis

Chronic kidney

disease

Multiple sclerosis Sinusitis Liver disease

Asthma Stroke Chronic obstructive

pulmonary disease

Psoriasis/eczema

Atrial fibrillation Blindness Bronchiectesis Irritable bowel

syndrome

Epilepsy Glaucoma Crohn’s disease Migraine

Cancer (any) Hearing loss Diverticulitis Dyspepsia

Thyroid disorders Hypertension Rheumatoid

arthritis

Constipation

Diabetes Heart failure Prostate disease Pain disorder

Prevalence and odds ratios for physical health comorbidity (standardised by age and gender)

Variable Bipolar, n (%) Not bipolar, n (%) Odds ratio (95% CI)

No physical condition 929 (36.0) 799,179 (56.2) 0.59 (0.54 to 0.63)

One physical condition 662 (25.6) 292,651 (20.6) 1.27 (1.16 to 1.39)

Two physical

comorbidities 427 (16.5) 149,297 (10.5) 1.45 (1.30 to 1.62)

Three or more physical

comorbidities 564 (21.8) 180,669 (12.7) 1.44 (1.30 to 1.64)

Prevalence and odds ratios for physical health comorbidity (standardised by age and gender)

Variable Bipolar, n (%) Not bipolar, n (%) Odds ratio (95% CI)

No physical condition 929 (36.0) 799,179 (56.2) 0.59 (0.54 to 0.63)

One physical condition 662 (25.6) 292,651 (20.6) 1.27 (1.16 to 1.39)

Two physical

comorbidities 427 (16.5) 149,297 (10.5) 1.45 (1.30 to 1.62)

Three or more physical

comorbidities 564 (21.8) 180,669 (12.7) 1.44 (1.30 to 1.64)

Differences in prescribing between bipolar and controls for coronary heart

disease (CHD) and hypertension patients, standardised by age and gender.

Patients Bipolar Controls Odds ratio (95% CI)

CHD patients: n = 170 n = 80,985

Aspirin or clopidogrel, % 69.3 73.6 0.81 (0.58 to 1.12)

Statin, % 70.0 74.9 0.69 (0.50 to 0.96)

No antihypertensive, % 29.4 15.8 2.08 (1.49 to 2.91)

One antihypertensive, % 37.6 31.3 1.29 (0.94 to 1.76)

Two or more

antihypertensives, % 32.9 52.7 0.46 (0.33 to 0.63)

Hypertension patients: n = 462 n = 232,986

Statin, % 36.7 41.5 0.82 (0.68 to 0.98)

No antihypertensive, % 21.8 13.9 1.70 (1.36 to 2.12)

One antihypertensive, % 39.8 32.3 1.38 (1.15 to 1.67)

Two or more

antihypertensives, % 37.8 53.7 0.53 (0.44 to 0.68)

Differences in prescribing between bipolar and controls for coronary heart

disease (CHD) and hypertension patients, standardised by age and gender.

Patients Bipolar Controls Odds ratio (95% CI)

CHD patients: n = 170 n = 80,985

Aspirin or clopidogrel, % 69.3 73.6 0.81 (0.58 to 1.12)

Statin, % 70.0 74.9 0.69 (0.50 to 0.96)

No antihypertensive, % 29.4 15.8 2.08 (1.49 to 2.91)

One antihypertensive, % 37.6 31.3 1.29 (0.94 to 1.76)

Two or more

antihypertensives, % 32.9 52.7 0.46 (0.33 to 0.63)

Hypertension patients: n = 462 n = 232,986

Statin, % 36.7 41.5 0.82 (0.68 to 0.98)

No antihypertensive, % 21.8 13.9 1.70 (1.36 to 2.12)

One antihypertensive, % 39.8 32.3 1.38 (1.15 to 1.67)

Two or more

antihypertensives, % 37.8 53.7 0.53 (0.44 to 0.68)

Implications:

• Coronary Heart Disease, Heart Failure, Peripheral Vascular

Disease, Stroke and TIA not more commonly recorded in the bipolar group

• Where cardiovascular diseases were recorded for the bipolar group, evidence of less intensive treatment

• Substantial treatment inequalities for bipolar patients with

coronary heart disease and hypertension.

UK data:

• Bipolar Disorder Research Network (n=8,000)

• Scottish Primary Care data (n=1.8 million)

• UK Biobank (n=0.5 million)

• Glasgow Psychosis cohort (n=7,500)

Mood disorder, cardiovascular disease and

the impact of psychotropic medication

(Martin et al, under review)

0

5

10

15

20

25

30

35

40

45

None One Two Three > Four

Bipolar Disorder (n=1,608)

MDD (n=31,756)

Controls (n=116,079)

Number of comorbidities

%

0

5

10

15

20

25

30

35

40

Any cardiovascular disease

Hypertension Diabetes

Bipolar Disorder (n=1557)

MDD (n=30,990)

Controls (n=113,444)

%

Partially adjusted a Fully adjusted b

OR (95% CI) OR (95% CI)

CVD any:

Control 1 1

Depression 1.29 (1.25, 1.33) 1.15 (1.12, 1.19)

Bipolar 1.50 (1.34, 1.68) 1.28 (1.14, 1.43)

Hypertension:

Control 1 1

Depression 1.27 (1.23, 1.31) 1.15 (1.11, 1.18)

Bipolar 1.44 (1.29, 1.61) 1.26 (1.12, 1.42)

Diabetes:

Control 1 1

Depression 1.29 (1.22, 1.37) 1.07 (1.00, 1.13)

Bipolar 1.37 (1.12, 1.67) 1.01 (0.81, 1.24)

A Partially adjusted: age, sex, deprivation and ethnicity B Fully adjusted: age, sex, deprivation, ethnicity, BMI, smoking status, alcohol consumption and current use of

psychotropic medication.

Diabetes

(N=7,825)

OR and 95%CI

MI

(N=3,129)

OR and 95%CI

Angina

(N=4,222)

OR and 95%CI

Hypertension

(N=38,840)

OR and 95%CI

Stroke

(N=2,066)

OR and 95%CI

Controls, no psychotropic

medication

1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)

Controls on psychotropic

medication

1.91

1.70, 2.14

1.85

1.54, 2.21

2.26

1.96, 2.61

1.59

1.48, 1.70

3.28

2.76, 3.90

Cardiometabolic disease, mood disorder and psychotropic medication (adjusted for age, sex, social deprivation, ethnicity)

Diabetes

(N=7,825)

OR and 95%CI

MI

(N=3,129)

OR and 95%CI

Angina

(N=4,222)

OR and 95%CI

Hypertension

(N=38,840)

OR and 95%CI

Stroke

(N=2,066)

OR and 95%CI

Controls, no psychotropic

medication

1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)

Controls on psychotropic

medication

1.91

1.70, 2.14

1.85

1.54, 2.21

2.26

1.96, 2.61

1.59

1.48, 1.70

3.28

2.76, 3.90

MDD, no psychotropic

medication

1.15

1.08, 1.23

1.33

1.21, 1.47

1.33

1.22, 1.45

1.21

1.18, 1.26

1.45

1.29, 1.63

MDD on psychotropic

medication

2.12

1.93, 2.33

1.83

1.55, 2.15

2.57

2.28, 2.91

1.63

1.54, 1.73

2.97

2.54, 3.48

Cardiometabolic disease, mood disorder and psychotropic medication (adjusted for age, sex, social deprivation, ethnicity)

Diabetes

(N=7,825)

OR and 95%CI

MI

(N=3,129)

OR and 95%CI

Angina

(N=4,222)

OR and 95%CI

Hypertension

(N=38,840)

OR and 95%CI

Stroke

(N=2,066)

OR and 95%CI

Controls, no psychotropic

medication

1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)

Controls on psychotropic

medication

1.91

1.70, 2.14

1.85

1.54, 2.21

2.26

1.96, 2.61

1.59

1.48, 1.70

3.28

2.76, 3.90

MDD, no psychotropic

medication

1.15

1.08, 1.23

1.33

1.21, 1.47

1.33

1.22, 1.45

1.21

1.18, 1.26

1.45

1.29, 1.63

MDD on psychotropic

medication

2.12

1.93, 2.33

1.83

1.55, 2.15

2.57

2.28, 2.91

1.63

1.54, 1.73

2.97

2.54, 3.48

Bipolar disorder, no

psychotropic medication

1.43

1.17, 1.75

2.03

1.53, 2.68

1.82

1.40, 2.36

1.48

1.32, 1.66

1.98

1.40, 2.81

Bipolar disorder on

psychotropic medication

2.21

1.62, 3.00

3.10

2.04, 4.71

2.22

1.46, 3.39

1.65

1.36, 2.00

2.95

1.78, 4.90

Cardiometabolic disease, mood disorder and psychotropic medication (adjusted for age, sex, social deprivation, ethnicity)

Chronic multisite pain in major depression

and bipolar disorder: cross-sectional study of

149,612 participants in UK Biobank.

(Nicholl et al, under review)

• Definition of multisite pain:

“In the last month have you experienced any of the following

that interfered with your usual activities?”

– Headache pain

– Facial pain

– Neck or shoulder pain

– Back pain

– Stomach or abdominal pain

– Hip pain

– Knee pain

– “Pain all over the body” (widespread)

RRR (95% CI)*

Model Depression Bipolar disorder

1. Unadjusted (n=149,612)

No chronic pain 1 1

1 site 1.35 (1.31, 1.39) 1.41 (1.24, 1.60)

2-3 sites 1.88 (1.81, 1.94) 2.35 (2.07, 2.38)

4-7 sites 3.12 (2.91, 3.34) 4.43 (3.55, 5.52)

Widespread pain 2.80 (2.53, 3.11) 5.38 (4.04, 7.16)

1. Adjusted for sex, age, ethnicity,

deprivation, employment

status BMI, smoking status

frequency of alcohol

consumption, comorbidity

count (n=145,518)

No chronic pain 1 1

1 site 1.27 (1.23, 1.31) 1.27 (1.12, 1.45)

2-3 sites 1.59 (1.54, 1.65) 1.84 (1.61, 2.11)

4-7 sites 2.13 (1.98, 2.30) 2.39 (1.88, 3.03)

Widespread pain 1.86 (1.66, 2.08) 2.37 (1.73, 3.23)

RRR (95% CI)*

Model Depression Bipolar disorder

1. Unadjusted (n=149,612)

No chronic pain 1 1

1 site 1.35 (1.31, 1.39) 1.41 (1.24, 1.60)

2-3 sites 1.88 (1.81, 1.94) 2.35 (2.07, 2.38)

4-7 sites 3.12 (2.91, 3.34) 4.43 (3.55, 5.52)

Widespread pain 2.80 (2.53, 3.11) 5.38 (4.04, 7.16)

1. Adjusted for sex, age, ethnicity,

deprivation, employment

status BMI, smoking status

frequency of alcohol

consumption, comorbidity

count (n=145,518)

No chronic pain 1 1

1 site 1.27 (1.23, 1.31) 1.27 (1.12, 1.45)

2-3 sites 1.59 (1.54, 1.65) 1.84 (1.61, 2.11)

4-7 sites 2.13 (1.98, 2.30) 2.39 (1.88, 3.03)

Widespread pain 1.86 (1.66, 2.08) 2.37 (1.73, 3.23)

RRR (95% CI)*

Model Depression Bipolar disorder

1. Unadjusted (n=149,612)

No chronic pain 1 1

1 site 1.35 (1.31, 1.39) 1.41 (1.24, 1.60)

2-3 sites 1.88 (1.81, 1.94) 2.35 (2.07, 2.38)

4-7 sites 3.12 (2.91, 3.34) 4.43 (3.55, 5.52)

Widespread pain 2.80 (2.53, 3.11) 5.38 (4.04, 7.16)

1. Adjusted for sex, age, ethnicity,

deprivation, employment

status BMI, smoking status

frequency of alcohol

consumption, comorbidity

count (n=145,518)

No chronic pain 1 1

1 site 1.27 (1.23, 1.31) 1.27 (1.12, 1.45)

2-3 sites 1.59 (1.54, 1.65) 1.84 (1.61, 2.11)

4-7 sites 2.13 (1.98, 2.30) 2.39 (1.88, 3.03)

Widespread pain 1.86 (1.66, 2.08) 2.37 (1.73, 3.23)

7,250 patients with psychotic disorder registered (2013):

– schizophrenia (n=4,787)

– bipolar disorder (n=1,784)

– organic psychosis (n=67)

– psychotic depression (n=452)

– substance-induced psychosis (n=160)

Baseline and annual follow-up information:

ICD-10 diagnosis, Community Health Index (CHI) number, ethnicity, marital status, accommodation status and postcode, employment status, educational attainment, family history of psychosis, psychiatric admissions data, current illness severity (including CGI and HoNOS scores), use of the mental health act, current and previous medications, adverse drug effects, psychosocial interventions received and psychiatric comorbidities.

0

100

200

300

400

500

600

700

800

900

Least deprived 2 3 4 Most deprived

De

ath

s p

er

10

,00

0 p

er

5 y

ear

s

Death rates in Major Mental Illness (MMI) by social deprivation: Glasgow and Scotland

MMI

Glasgow

Scotland

Langan Martin et al, BMC Psychiatry, in press.

0

100

200

300

400

500

600

700

800

900

Least deprived 2 3 4 Most deprived

De

ath

s p

er

10

,00

0 p

er

5 y

ear

s

Death rates in Major Mental Illness (MMI) by social deprivation: Glasgow and Scotland

MMI

Glasgow

MMI Excluding Suicide

Scotland

Langan Martin et al, BMC Psychiatry, in press.

NHS Greater Glasgow and Clyde:

SafeHaven

Dumb terminals

DWEducation

DW1

Anonymised servers

NHS Safe Haven

RCB

LPAC

decisions

Application

server

All clinical

datasets

Safe

Have

n G

overn

ance

Data

Requests

Clinical Trials

Research Data

Safe Haven – IT Infrastructure

Db3

Db2

SQL cluster

Clinical Non

health

Db1 Dataset

Dataset CHI

Seeded

Non health

data

Non

health

Clinical

Data is now in a

data warehouse

structure using only

surrogate keys to

link

DWSocialWork

DWEducation

DWSocialWork

DW1

Current Datasets •Datasets in Safe Haven

– SMR00 - Outpatient Attendance

– SMR01 – Acute inpatient & Day Care

– SMR02 – Maternity

– SMR04 – Mental Health

- CHI – GG&C patient population (1.3 million)

- GRO – Births and deaths date for GG&C

- ePrescribing – encashed prescriptions for Glasgow

- GP (LES and Keep Well) 250 practices

- Heart Failure – locally held national Heart Failure database

- Rheumatology – local clinical database

- SCI DC – GGC population of national Diabetic database

- SCI Store results for GGC

- Parkinson – local clinical database for Movement disorders

- Weight Management

- PsyCIS – schizophrenia database

- Clozapine database

- EDIS (A&E now replaced by Trak care)

• REC approval is to submit an amendment every time 6 new databases are added

• In discussion to extend health data to other Boards in NRS West – Lanarkshire, A&A, D&G and Golden Jubilee

P O P U L A T I O N

S P I N E

H E A L T H

D A T A

Clinical Trial Support e Feasibility, e Recruitment, e Data capture & f/up

Real World Clinical Studies Virtual case/control cohorts, epidemiology, pharmaco-

epidemiology

Actionable Data Analytical tools, visual analytics

Health Economic analyses

Increased efficiency &

effectiveness of NHS services

Enrichment with other data sets Education

Social work Housing

Transport Police

CHI linkage CHI seeding and linkage

Virtual population-wide cohorts

e.g. birth, geriatric Followed longitudinally

Understanding, improving and integrating services

Centre for Data-Driven Research & Innovation (name to be decided)

UK data:

• Bipolar Disorder Research Network (n=8,000)

• Scottish Primary Care data (n=1.8 million)

• UK Biobank (n=0.5 million)

• Glasgow Psychosis cohort (n=7,500)

Bipolar Disorder Research Network:

Nick Craddock, Ian Jones, Liz Forty, Lisa Jones

Scottish Primary Care data:

Stewart Mercer, Bruce Guthrie, Gary McLean, Julie Langan Martin

UK Biobank:

Jill Pell, Daniel Martin, Barbara Nicholl, Daniel Mackay

Glasgow Psychosis cohort:

Moira Connolly, John Park, Julie Langan Martin

Thanks

Physical comorbidity with bipolar disorder: lessons from UK data

Daniel Smith

daniel.smith@glasgow.ac.uk

Symposium 33: ‘Big data’ and bipolar disorder in the UK

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