Stroke and depression: A bidirectional link

Table 1 Risk of stroke according to depression status in prospective studies

Ref.	Population	Follow-up years, (period)	No. of stroke cases	Risk of total stroke (95%CI)	Risk of ischemic stroke (95%CI)	Risk of hemorrhagic stroke (95%CI)	Adjustment for covariates and confounders	Depression assessment	Stroke ascertainment
Vogt et al[10]	2573 Men and women aged ≥ 18 yr	15 (1970/71-1985)	NA	HR 0.84 (0.57-1.22)			Age, sex, socioeconomic status, length of health plan membership, subjective health status, smoking	Depressive index	Death index or vital records
Wassertheil-Smoller et al[11]	4367 Men and women aged ≥ 60 yr	4.5 (1985-1990)	204	RR 0.85 (0.45-1.64)			Age, baseline depression, race, education, smoking, diabetes, history of CVD, activities of daily living	CES-D	Medical records
Everson et al[12]	6676 Men and women aged 16-94 yr	29 (1965-1983)	169	RR 1.54 (1.06-2.22)			Age, sex, race, education, hypertension, diabetes, smoking status, alcohol, BMI	HPL Depression Scale	Death certificates
Whooley et al[13]	7518 Women aged ≥ 65 yr	6 (1988-1994)	94	HR 1.7 (0.8-3.5)			Age, history of MI, stroke, hypertension, diabetes, smoking, perceived health, cognitive function	GDS	Medical records
Jonas et al[14]	6095 Men and women aged 25-74 yr	16 (1971/75-1992)	483	RR 1.73 (1.30-2.31)			Age, SBP, education, smoking, BMI, alcohol, physical activity, cholesterol, diabetes, history of heart disease	GWS	Hospital records and death certificates
Larson et al[15]	1703 Men and women aged ≥ 18 yr	13 (1980/1983-1993/1996)	95	OR 2.67 (1.08-6.63)			Age, sex, race, educational attainment, smoking status, history of diabetes, heart problems, high blood pressure	DIS	Self-report and death certificates
Ohira et al[16]	879 Men and women aged 40-78 yr	10.3 (1985-1996)	69	RR 1.9 (1.1–3.5)	RR 2.7 (1.2–6.0)	RR 0.9 (0.3–3.1)	Age, sex, smoking status, alcohol use, BMI, SBP, serum total cholesterol level, current treatment with antihypertensive medication, and history of diabetes	Zung SDS	National insurance claims, medical records, clinical diagnosis and death certificates
Ostir et al[17]	2478 Men and women aged ≥ 65 yr	6 (1986-1992)	340	RR 1.30 (0.85-1.99)			Age, sex, marital status, household income, education, smoking status, BMI, heart attack, diabetes, hypertension	CES-D	Self-report and death certificates
May et al[18]	2124 Men aged 45-59 yr	14 (1984/1988-1998)	130		HR 1.26 (0.85–1.85)		Age, social class, marital status, smoking status, alcohol use, BMI, SBP, comorbidity (ischemic heart disease, diabetes, respiratory disease, or retirement due to ill health)	GHQ	Medical records
Wassertheil-Smoller et al[19]	93676 Women aged 50-79 yr	4.1 (1993/1998-2000)	751	RR 1.01 (0.78-1.3)1; 1.45 (1.11-1.9)2			Age, race, education, income, smoking status, BMI, physical activity, hormone use, high cholesterol level requiring medications, diabetes, and hypertension	CES-D and DIS	Self-report and medical redords
Gump et al[20]	11216 Men aged 35-57 yr	18.4 (1979/1981-1999)	167	HR 1.48 (0.93-2.36)			Age, intervention group, race, educational attainment, smoking at baseline and visit 6, SBP, alcohol consumption, fasting cholesterol and the occurrence of nonfatal cardiovascular events during the trial	CES-D	Death certificates
Avendano et al[21]	2812 Men and women aged ≥ 65 yr	12 (1982-1994)	270	HR age 65-74: 3.05 (1.63–5.7); age ≥ 75: 0.95 (0.46–1.98)			Age, sex, race, education and income	CES-D	Self report and medical records
Stürmer et al[22]	3920 Men and women aged 40-65 yr	8.5 (1992/1995-2002/2003)	62	RR 1.53 (0.83-2.8)			Age, sex, education, smoking status, alcohol consumption, BMI, exercise, family histories of MI, stroke and cancer, comorbidity
Kamphuis et al[23]	799 Men aged 70-90 yr	7.4 (1989/1991-2000)	66	HR 3.41 (1.69-6.9)			Age, country, education, BMI, smoking, alcohol intake, blood pressure, cholesterol, and physical activity
Arbelaez et al[24]	5525 Men and women aged ≥ 65 yr	11 (1989-2000)	611	HR 1.25 (1.02–1.53)			Age, sex, race, occupation, income, education level, marital status, smoking status, BMI, blood cholesterol, highdensity lipoprotein cholesterol, lowdensity lipoprotein cholesterol, triglycerides levels, comorbidity (hypertension, diabetes, CHD), CRP
Kawamura et al[25]	535 Men and women aged ≥ 65 yr	6.3 (1985-2000)	103	RR 1.25 (0.82–1.90)			NA
Salaycik et al[26]	4120 Men and women aged ≥ 29 yr	8 (1990/1998-1998/2006)	228	HR Age < 65: 3.59 (1.76–7.3); Age ≥ 65: 0.93 (0.59–1.47)			Age, sex, smoking status, blood pressure, diabetes, atrial fibrillation, CVD, left ventricular hypertrophy on the ECG
Bos et al[27]	4424 Men and women aged ≥ 61 yr	5.8 (1997/1999-2005)	291	HR 1.21 (0.80–1.83)	HR 1.43 (0.87-2.35)		Age, sex, smoking status, SBP, intima–media thickness, medication use (antithrombotic drug, antihypertensive drug, cholesterol lowering drug, psycholeptic drug and psychoanaleptics drug), comorbidity (diabetes, MI, PTCA or CABG, TIA)
Lee et al[28]	4962 Men and women 18-44 yr	5 (1998-2003)	98	HR 5.43 (3.47-8.5)			Age, sex, geographic location, income, urbanization, substance abuse, comorbidity (diabetes, hypertension, hyperlipidemia, renal disease)
Liebetrau et al[29]	401 Men and women aged 85 yr	3 (1986/1987-1989/1990)	56	HR 2.6 (1.5-4.6)			NA
Surtees et al[30]	20627 Men and women aged 41-80 yr	8.5 (1996/2000-2006)	595	HR 1.08 (0.67–1.75)			Age, sex, social class, education, smoking status, obesity, SBP, total cholesterol, diabetes, hypertension treatment, MI, family history of stroke, and ADM use
Whooley et al[8]	20627 Men and women aged mean 63 yr and 68 yr3	4.8 (2000/2002-2008)	47	HR 1.47 (0.70-3.11)			Age, smoking, medication adherence, physical activity, CRP, left ventricular ejection fraction, history of MI, stroke, heart failure, diabetes
Glymour et al[31]	19087 Men and women aged ≥ 50 yr	8.1 (1996-2006)	1864	HR 1.25 (1.12- 1.39)			Age, overweight, ethnicity, birth place, parental educations, self education, income, wealth and marital status, year of enrollment, alcohol and smoking status, and self-reported diagnoses of hypertension, diabetes, or heart disease
Peters et al[33]	2656 Men and women aged ≥ 80 yr	2.1 (2001-2007)	97	HR 1.82 (1.19–2.78)			Age, sex, treatment group, treatment allocation, country area, educational level, living status, number of comorbidities, previous CVD, previous treatment for hypertension and hypertension
Pan et al[34]	80574 Women aged 54-79 yr	6 (2000-2006)	1033	RR 1.29 (1.13-1.48)	RR 1.11 (0.91-1.35)	RR 1.20 (0.80-1.79)	Age, marital status, ethnicity, smoking status, alcohol consumption, BMI, physical activity level, menopausal status, postmenopausal hormone therapy, current aspirin or multivitamin use, Dietary Approaches to Stop Hypertension dietary score, parental history of MI
Seifert et al[35]	3852 Men and women aged > 55 yr	6.1 (2001/2003-2009)	156	HR 1.3 (0.9-1.89)			Age, sex, BMI, smoking, hypertension, diabetes, hyperlipidemia, previous MI, previous TIA, previous stroke, history of atrial fibrillation, physical activity
Majed et al[36]	9601 Men aged 48-64 yr	10 (1991/1993-2003)	136	HR 1.41 (0.95-2.11)	HR 1.65 (1.07-2.55)		Age; study centers; socioeconomic factors, including marital status, education level, employment status, physical activity, smoking status, daily alcohol intake, SBP, use of anti-hypertensive drugs, BMI, total and high-density lipoprotein cholesterol, treatment for diabetes, ADM use.
Jackson et al[37]	10547 Women aged 47-52 yr	12 (1998-2010)	177	OR 1.94 (1.37- 2.74)			Age, education, homeownership, hypertension, diabetes mellitus, heart disease, hysterectomy/oophorectom, smoking, alcohol use, physical activity, BMI

¹No baseline CVD;

²With baseline CVD;

³Group with depression mean age 63 years, group without depression mean age 68 years. n Scale: Human Population Laboratory Depression Scale; GDS: Geriatric. CES-D: Center for Epidemiologic Studies Depression Scale; HPL Depression Depression Scale; GWS: General Well-Being Schedule; DIS: diagnostic interview schedule; Zung SDS: Zung Self-Rating Depression Scale; GHQ: General Health Questionnaire; ADM: Antidepressant medication; DSMMD: Diagnostic and Statistical Manual of Mental Disorders; HLEQ: Health and Life Experiences Questionnaire; PHQ: Patient Health Questionnaire; BDI: Beck Depression Inventory; MHI: Mental Health Index; CI: Confidence interval; NA: Not available; HR: Hazard ratio; RR: Relative risk; OR: Odds ratio; CVD: Cardiovascular disease; BMI: Body mass index; MI: Myocardial infarction; CHD: Coronary heart disease; CRP: C reactive protein; SBP: Systolic blood pressure; ECG: Electrocardiogram; PTCA: Percutaneous transluminal angioplasty; CABG: Coronary artery bypass graft.

Table 2 Pooled prevalence of post stroke depression stratified by study setting and timing assessment in the meta-analysis of Hackett et al^[6,147] and Ayerbe et al^[100,101]

	Hackett et al[6,147]	Ayerbe et al[100,101]
Publication period of included studies	1977-2002	1983-2011
Number of included studies (population: n, hospital: n, rehabilitation: n)	51 (population: 6, hospital: 16, rehabilitation: 29)	43 (population: 6, hospital: 15, rehabilitation: 22)
Pooled prevalence
Overall	33% (95%CI: 29%-36%)	29% (95%CI: 25%-32%)
Study setting
Population-based	AP: 33% (95%CI: 29%-37%) MTP: 33% (95% CI: 0%-72%) LTP: 33% (95%CI: 29%-36%)	22% (95%CI: 17%-28%)
Hospital-based	AP: 36% (95%CI: 0%-73%) MTP: 32% (95% CI: 23%-41%) LTP: 34% (95%CI: 24%-45%)	30% (95%CI: 24%-36%)
Rehabilitation-based	AP: 30% (95%CI: 16%-44%) MTP: 36% (95% CI: 20%-39%) LTP: 34% (95%CI: 26%-42%)	30% (95%CI: 25%-36%)
Timing of assessment
Acute phase (< 1 mo)	32% (95%CI: 19%-44%)	28% (95%CI: 23%-34%)
Medium-term phase (1-6 mo)	34% (95%CI: 20%-39%)	31% (95%CI: 24%-39%)
Long-term phase (6 mo or more)1 (6 mo to 1 yr)2	34% (95%CI: 29%-39%)	33% (95%CI: 23%-43%)
Very long-term phase (> 1 yr)	n.d.	25% (95%CI: 19%-32%)

AP: Acute phase; MTP: Medium-term phase; LTP: Long-term phase; n.d.: Not determined.