Hypertension predisposes to the formation of saccular intracranial aneurysms in 467 unruptured and 1053 ruptured patients in Eastern Finland

Figures & data

Table I. Previous studies on the association of hypertension and angiographically verified saccular intracranial aneurysms since 2000.

Reference (year)	Country	Type of study	Cases/controls	Matching of controls	Mean age ± SD (y), cases/controls	Hypertension, cases/controls	Multivariate analysis	Diagnosis of hypertension^a
aSAH versus matched controls
Shiue et al. (2012)	Australia	Case-control, multicenter, prospective	432 aSAH/473 controls	Age, sex, city-matched community controls	56.5 ± 16.8	189 (47%)/161 (34%)	OR 1.79 (1.29–2.50); P = 0.0007	Medical records and interview
Inagawa (2010)	Japan	Case-control, single center, prospective	798 aSAH/798 controls	Age, sex-matched from Izumo-Hikawa district	64 ± 12	431 (54%)/241 (30%)	OR 3.19 (2.51–4.05); P < 0.001	Medical records
Ruiz-Sandoval et al. (2009)	Mexico	Case-control, multicenter, retrospective	231 aSAH/231 controls	Age, sex-matched community controls	52	96 (42%)/67 (29%)	OR 2.46 (1.59–3.81); P < 0.005	Medical records, BP on admission
Okamoto et al. (2007)	Japan	Case-control, single center, prospective	201 aSAH/402 controls	Age, sex-matched community controls	59.1	47.8%/24.8%	OR 4.6 (2.8–7.8); P < 0.05	Antihypertensive therapy by interview
Ohkuma et al. (2003)	Japan	Case-control, multicenter, prospective	390 aSAH/390 controls	Age, sex-matched hospital controls	58 ± 13	181 (46%)/117 (30%)	OR 2.29 (1.66–3.16); P < 0.05	Interview
Kubota et al. (2001)	Japan	Case-control, multicenter, prospective	127 aSAH/127 controls	Age, sex-matched hospital controls	52 ± 10	52 (40%)/26 (20%)	OR 2.35 (1.57–3.53); P = 0.034	Structured questionnaire
aSAH versus unruptured sIA patients
Vlak et al. (2013)	Netherlands	Case-control, retrospective, single center	250 aSAH/206 unruptured sIAs	Age matched	54.7 ± 12.5/54.6 ± 11.6	61 (24.6%)/77 (38.1%)	n.s.	Medical records
You et al. (2008)	Korea	Case control, single center, prospective	167 aSAH/123 unruptured sIAs	Age, sex- et al. matched	53.5 ± 13.1/57.9 ± 10.1	59 (35.3%)/63 (51.2%)	OR 1.55 (0.86–2.79); P = 0.143	Medical records
Unruptured sIA patients versus matched controls
Vlak et al. (2013)	Netherlands	Case-control, retrospective, single center	206 unruptured sIAs/574 controls	Age and sex-matched	54.6/54.8	77 (38.1%)/104 (19%)	OR 2.9 (1.9–4.6); P < 0.05	Medical records
Inagawa (2010)	Japan	Case-control, single center, prospective	266 unruptured sIAs/798 controls	Age, sex-matched from Izumo-Hikawa district	66 ± 11	154 (58%)/241 (30%)	OR 3.26 (2.39–4.46); P < 0.001	Medical records
Unruptured sIA patients
UCAS Japan (2012)	Japan	Prospective, multicenter	5720 patients with 6697 unruptured sIAs		62.5 ± 10.3	2480 (43.4%)		Interview
Guresir et al. (2013)	Germany	Prospective, single center	263 patients with 384 unruptured sIAs		55 ± 12	112 (42.6%)		Interview

^aIn all cohorts, the diagnosis of hypertension was made before the diagnosis of unruptured sIA disease or the time of aSAH.

aSAH = aneurysmal subarachnoid hemorrhage; IA = intracranial aneurysm; sIA = saccular intracranial aneurysm; BP = blood pressure; OR = odds ratio in multivariate analysis; n.s. = not significant.

Table II. Indications for diagnostic neuroimaging in 467 unruptured sIA patients in 1995–2007 from Eastern Finland.

	No AHTM in follow-up (n = 124)	AHTM started before or after sIA diagnosis (n = 343)
Incidental sIA	100 (81%)	283 (83%)
Median size (mm) (quartiles)	5 (3–8)	6 (4–9)
Headache	19	50
Brain infarction or TIA	4	37
Vertigo	8	27
Amnesia	3	15
Trauma	6	14
Other	55	115
Unknown	4	25
Screening for familial sIA	15 (12%)	30 (9%)
Median size (mm) (quartiles)	5 (3–6)	4 (3–6)
Symptomatic sIA	9 (7%)	30 (9%)
Median size (mm) (quartiles)	14 (7–30)	17 (9–28)
Vision defect	3	12
Epileptic seizure	0	5
Hemiparesis	2	8
Other	4	5

AHTM = antihypertensive medication; sIA = saccular intracranial aneurysm; TIA = transient ischemic attack.

Table III. Clinical characteristics of 1520 sIA patients in 1995–2007 from Eastern Finland.

	Unruptured sIA patients n = 467			Ruptured sIA (sIA-SAH) patients n = 1053
	No AHTM in follow-up, n = 124 (26%)	AHTM started before sIA diagnosis, n = 237 (51%)	AHTM started after sIA diagnosis, n = 106 (23%)	No AHTM in follow-up, n = 404 (38%)	AHTM started before sIA diagnosis, n = 348 (33%)	AHTM started after sIA diagnosis, n = 301 (29%)
Males	56/195 (29%)	101/195 (52%)	38/195 (19%)	201/449 (45%)	117/449 (26%)	131/449 (29%)
Females	68/272 (25%)	136/272 (50%)	68/272 (25%)	203/604 (34%)	231/604 (38%)	170/608 (28%)
sIA disease diagnosis
Median age (quartiles)	49 (43–56)	58 (50–68)	54 (46–64)	51 (43–61)	60 (51–69)	51 (43–61)
Females	50 (43–57)	59 (51–70)	54 (47–65)	53 (44–66)	60 (51–70)	55 (46–65)
Familial sIA disease	38 (31%)	51 (22%)	38 (36%)	49 (12%)	46 (13%)	49 (16%)
Multiple sIAs (≥ 2)	30 (24%)	63 (27%)	30 (28%)	100 (25%)	110 (32%)	83 (28%)
Characteristics of sIAs
Median size of sIA (mm) (quartiles)	5 (3–7)	5 (3–8)	5 (3–8)	7 (5–10)	7 (4–10)	6 (4–9)
Location of sIAs	171 sIAs	337 sIAs	151 sIAs	404 sIAs	347 sIAs	301 sIAs
ACoA	17 (10%)	49 (15%)	15 (10%)	115 (28%)	91 (26%)	102 (34%)
Mbif	82 (48%)	131 (39%)	59 (39%)	113 (28%)	92 (27%)	94 (31%)
ICA	37 (22%)	88 (26%)	44 (29%)	104 (26%)	71 (21%)	55 (18%)
BAbif	6 (4%)	22 (7%)	9 (6%)	15 (4%)	29 (8%)	8 (3%)
Others	29 (17%)	47 (14%)	24 (16%)	57 (14%)	64 (18%)	42 (14%)
Antihypertensive medication	124 (26%)	237 (51%)	106 (23%)	404 (38%)	348 (33%)	301 (29%)
Median starting age (quartiles)		53 (47–63)	56 (50–68)		55 (47–65)	54 (46–65)
Females		54 (46–65)	56 (50–70)		56 (48–65)	57 (49–68)
Statin medication	26 (21%)	138 (58%)	26 (25%)	43 (11%)	131 (38%)	125 (42%)
Median starting age (quartiles)	56 (50–66)	61 (52–68)	57 (50–64)	57 (50–62)	62 (56–70)	58 (51–66)
Antidiabetic medication	4 (3%)	32 (14%)	8 (6%)	14 (3%)	44 (13%)	34 (11%)
Median starting age (quartiles)	53 (41–62)	66 (58–71)	62 (57–69)	56 (53–63)	63 (57–69)	62 (51–72)
Smoking
Current	47 (38%)	80 (34%)	47 (38%)	149 (37%)	73 (21%)	131 (44%)
Former	11 (9%)	25 (11%)	11 (9%)	29 (7%)	30 (9%)	31 (10%)
No	66 (53%)	131 (55%)	66 (53%)	85 (21%)	130 (37%)	104 (35%)
Unknown smoking status	0 (%)	1 (%)	0 (%)	141 (35%)	115 (33%)	35 (12%)
Condition on admission for sIA-SAH
Hunt and Hess Scale
I Asymptomatic				58 (14%)	37 (11%)	31 (10%)
II Moderate to severe headache				108 (27%)	123 (35%)	157 (51%)
III Drowsiness/confusion				87 (22%)	79 (23%)	73 (25%)
IV Stupor				80 (20%)	58 (17%)	36 (13%)
V Decerebrate posturing				71 (18%)	51 (14%)	4 (2%)
Intracerebral hemorrhage				126 (31%)	88 (25%)	74 (25%)
Intraventricular hemorrhage				129 (32%)	108 (31%)	60 (20%)
Acute hydrocephalus				198 (49%)	174 (50%)	110 (37%)
Occlusive therapy of sIA
Clipping	60 (48%)	104 (44%)	52 (49%)	235 (58%)	170 (49%)	194 (65%)
Embolization	12 (10%)	28 (12%)	16 (15%)	102 (25%)	121 (35%)	102 (34%)
None	52 (42%)	105 (44%)	38 (36%)	67 (17%)	57 (16%)	5 (2%)
Glasgow Outcome Scale at 12 months
5 Good recovery				179 (44%)	159 (46%)	226 (75%)
4 Moderate disability				47 (12%)	51 (15%)	59 (20%)
3 Severe disability				22 (5%)	18 (5%)	14 (5%)
2 Persistent vegetative state				2 (%)	4 (1%)	1 (%)
1 Death	4 (3%)	14 (6%)	0	154 (38%)	116 (33%)	1 (%)

ACoA = anterior communicating artery; AHTM = antihypertensive medication; BAbif = basilar artery bifurcation; ICA = internal carotid artery; Mbif = middle cerebral artery bifurcation; sIA = saccular intracranial aneurysm; sIA-SAH = subarachnoid hemorrhage from ruptured sIA.

Figure 2. Correlation of the age at diagnosis with the diameter of unruptured saccular intracranial aneurysms (sIAs) and ruptured ones (sIA-SAH). Regression lines and 95% confidence intervals (CIs) are shown for unruptured (continuous lines) and ruptured (dotted lines) patients. A and B: The patients without (A) versus with (B) antihypertensive medication during follow-up. The sIA diameter data were available for 320 unruptured sIA patients and 1052 ruptured sIA patients. C and D: The patients without (C) versus with (D) history of smoking (former or current) until the sIA diagnosis. The sIA diameter data and smoking data were available for 319 (182 in C and 137 in D) unruptured sIA patients and 318 (114 in C and 204 in D) ruptured sIA patients. The unruptured sIAs that caused symptoms were removed from the analysis.

Figure 1. Incidence of hypertension in 467 unruptured saccular intracranial aneurysm (sIA) patients and 1053 ruptured ones (sIA-SAH) by the 10-year age groups and their 95% confidence intervals. A: Patients with antihypertensive medication started before the sIA diagnosis. Follow-up time ends at the start of antihypertensive medication or the time of sIA diagnosis. B: Patients with antihypertensive medication started before or after the sIA diagnosis. Follow-up time ends at the start of antihypertensive medication, death, or 31 December 2008.