The association between orthostatic hypotension and cognition and stroke: a meta-analysis of prospective cohort studies

Figures & data

Figure 1. Flow diagram of the detailed process of selection of articles.

Table 1. Characteristics of the included studies.

Study	Country	Population	Outcome	Screening criteria	Main findings
Elmstáhl et al. [16]	Sweden	Community dwelling individuals aged 60 to 93 years	Dementia	DSM-IV	OH seemed to be a risk factor for CD.
Elmstáhl et al. [16]	Sweden	Community dwelling individuals aged 60 to 93 years	CI	Drop in MMSE of ≥1 point	OH seemed to be a risk factor for MCI.
Wolters et al. [17]	Netherlands	Community dwelling individuals ≥65 years	Dementia	DSM-III-R	OH was associated with an increased risk of dementia (adjusted HR: 1.15, 1.00–1.34).
Holm et al. [18]	Sweden	Population-based individuals with a mean age of 45 years	Dementia AD; VaD	DSM-III-R	OH was not significantly associated with dementia.
Cremer et al. [19]	France	Participants aged ≥65 years	Dementia	DSM-IV	OH measurements helped to identify subjects with a higher risk of dementia.
Rawlings et al. [15]	USA	Community-dwelling individuals with a mean age of 54.5 years	Dementia	ICD-9	OH was related to higher risk of dementia.
Peters et al. [20]	13 countries	Hypertensive adults mean aged 83.5 years	Dementia	DSM-IV	OH was related to higher risk of dementia.
Peters et al. [20]	13 countries	Hypertensive adults mean aged 83.5 years	CI	MMSE ≤24 or a drop in MMSE of ≥ 3 points	OH was related to higher risk of cognitive decline (HR = 1.39,1.19–1.62).
Yap et al. [21]	China	Community dwelling aged ≥65 years with no history of stroke or cardiovascular disease cardiovascular disease	CI	MMSE< 24	OH was not associated with cognitive impairment.
Yap et al. [21]	China	Community dwelling individuals aged ≥65 years with no history of stroke or cardiovascular disease cardiovascular disease	CD	Drop in MMSE of ≥1 point	OH was not associated with cognitive impairment.
Huang et al. [22]	China	Geriatric unit outpatients and controls >60 years.	CI	RBANS CAMCOG MMSEMMSE ≤24	OH was a risk factor for cognitive impairment (OR = 4.05, 1.14 –14.31).
Curreri et al. [23]	Italy	Community dwelling older adults, cognitively normal at baseline	CI	MMSE ≤24	OH did not predict cognitive impairment.
Curreri et al. [23]	Italy	Community dwelling older adults, cognitively normal at baseline	CD	Drop in MMSE of ≥3 points	OH did not predict cognitive decline.
Casiglia et al. [24]	Italy	Community-dwelling adults ≥65 years	Stroke	ICD-9	OH was not associated with stroke (HR = 1.33, 0.78–2.22).
Verwoert et al. [25]	Netherlands	Community-living adults >55 years	Stroke	ICD -10	OH was not associated with stroke (HR = 1.1, 0.89–1.36).
Fedorowski et al. (MPP) [26]	Sweden	Population-based individuals aged 45 to 64 years	Stroke	ICD-9 and ICD-10	OH was related to first stroke (HR = 1.11, 0.95–1.30).
Lin et al. [27]	China	Adults aged ≥65 years	Stroke	Clinical diagnosis	OH was not associated with stroke (HR = 1.09, 0.51–2.33).
Fedorowski et al. (CPP) [28]	Sweden	Hypertensive population aged 45 to 64 years	Stroke	Typical symptoms or signs of remaining neurological deficit with sudden onset and persistence for more than 24 h	OH was associated with stroke (HR = 1.48, 1.07–2.05).
Alagiakrishnan et al. [29]	USA	Community-dwelling adults ≥65 years	Stroke	Medical record review	OH had no significant association with stroke (HR = 1.18, 0.97–1.44).
Chou et al. [30]	China	Population-based individuals with a mean age of 54.8 years	Ischaemic stroke	Computed tomography or magnetic resonance imaging. ICD-9-CM	OH was associated with a higher risk of ischaemic stroke (HR = 1.40, 1.09–1.81).
Rawlings et al. [15]	USA	Community-dwelling adults ≥54.5 years	Ischaemic stroke	Medical record review	OH had a higher risk of ischaemic stroke (HR = 2.08, 1.65–2.62).
Yasa et al. [31]	Sweden	Adults with a mean age of 58 years	Stroke	ICD-9 and ICD-10	OH-hospitalization predicted stroke (HR = 1.66, 1.24–2.23).
Fleg et al. [32]	Multiple countries	Adults with a mean age of 62.1 years	Total stroke	Medical record review	Consensus OH at most recent visit did not increase the risk of total stroke (HR = 0.64, 0.26–1.61).

CAMCOG: cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly; MCI: mild cognitive impairment; OH: orthostatic hypotension; MMSE: mini mental state examination; DSM: diagnostic and statistical manual of mental disorders; ICD: international classification of diseases; CD: cognitive decline; CI: cognitive impairment.

Table 2. Characteristics of studies included in the meta-analysis.

Author	Year	Follow-up (years)	Sample size	Mean age (years)	Men (%)	Diabetes (%)	Hypertension (%)	BMI (kg/m^2)	OH (%)
Elmstáhl et al. [16]	2014	6	1480	68.0	46	5.4	59	N	19
Wolters et al. [17]	2016	15.3	6204	68.5	40.3	7.2	30.7	26.3	18.6
Holm et al. [18]	2017	28	18,240	45	63	3.1	34.6	24	2.1
Cremer et al. [19]	2017	12	7425	73.51	39.91	7.5	40.72	25.68	13
Rawlings et al. [15]	2018	25	11,709	54.5	43.6	11	38.5	27.6	4.7
Peters et al. [20]	2018	2	3121	83.5	39.5	9.6	N	N	17.2
Yap et al. [21]	2008	2	1347	65.5	34.2	15.4	44.4	23.5	16.6
Huang et al. [22]	2017	3	114	69.58	51.1	18.2	N	N	33.3
Curreri et al. [23]	2016	4.4	1408	71.4	40.6	13.5	10.9	27.8	18.3
Casiglia et al. [24]	2013	9.3	1016	71.7	41.2	26.8	N	27.3	16.5
Verwoert et al. [25]	2008	6.8	5064	68.1	38.4	8.9	26.9	26.2	17.8
Fedorowski et al. MPP [26]	2010	22.7	32,797	45.6	68.2	4.8	40.3	24.6	6.6
Lin et al. [27]	2011	1.1	1174	81.1	95.6	41.2	72.3	25.1	25.6
Fedorowski et al. CPP [28]	2013	6	8788	52.3	52.2	6.2	100	27.9	12.1
Alagiakrishnan et al. [29]	2013	13	3510	74	42	16.6	59.2	25.9	25.2
Chou et al. [30]	2015	4.5	13,486	54.8	47	24.8	42.4	N	0.09
Rawlings et al. [15]	2018	25	11,709	54.5	43.6	11.2	38.5	27.6	4.7
Yasa et al. [31]	2018	15	30,528	58	40	3.4	61	26	1.6
Fleg et al. [32]	2016	3.9	4266	62.1	53.4	100	100	32.1	20.1

N: not available.

Figure 2. Forest plot of the association between OH and worse cognition.

Figure 3. Forest plot of the association between OH and dementia.

Table 3. Summary of effect measure (HR and 95% CI).

Group	No. of studies	Test of association			Test of heterogeneity
		HR (95% CI)	Z	p	χ^2	p	I^2 (%)	Model
Cognition	13	1.18 (1.03–1.35)	2.42	.016	39.36	<.001	69.5	R
Dementia	6	1.30 (1.14–1.48)	4.00	<.001	7.25	.203	31	R
Stroke	10	1.36 (1.1 7–1.57)	4.07	<.001	27.52	.001	67.3	R

Figure 4. Forest plot of the association between OH and stroke.

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