Prevalence and development of aortic dilation and dissection in women with Turner syndrome: a systematic review and meta-analysis

Figures & data

Figure 1. Flowchart of article selection.

Table 1. Patient characteristics at baseline of the included studies.

First author, year	n	Age (years)	BSA (mm/m2)	45,X (%)	BAV (%)	COA (%)	HT (%)	HL (%)	DM (%)	GH (%)	ERT (%)
Price 1986 [27]	156	-	-	51.3	-	2.6	-	-	-	-	-
Sybert 1998 [28]	244	18.4 ± 13.7	-	53.7	11.5	13.9	12.3	-	-	-	-
Ostberg 2004 [29]	128	29.2 (18.7–55.5)	1.50 ± 0.18	49.2	18.3	1.7	-	-	5.5	31.3	100
Gravholt 2006 [30]	783	-	-	-	-	-	-	-	-	-	-
Matura 2007 [17]	166	36.2 ± 11.3	1.54 ± 0.2	82.3	18.7	-	-	-	-	-	-
Elsheikh 2008 [31]	38	29 (16–47)	-	47.4	31.6	5.3	50	-	-	-	-
Mortensen 2011^a [32]	80	38 ± 10	1.5 ± 0.2	60	27.8	11.2	30.0	-	-	27.5	85.0
Mortensen 2013^a [33]	102	38 ± 11	1.5 ± 0.2	58	25	12	29.4	5.9	4.9	27	86.3
De Groote 2015 [34]	74	29.4 ± 8.5	-	-	25.7	8.1	41.9	-	-	-	86.5
Prakash 2016 [35]	430	26.2[15-42]	1.48 [1.22–1.67]	67.5	41.9	18.7	-	-	-	-	-
Calanchini 2018 [36]	125	35 (18–73)	-	43.2	19.2	8.8	27.2	15.2	10.4	48.0	87.2
Duijnhouwer 2019^b [14]	268	28.7 [21.3-39.7]	1.57 [1.47–1.70]	40.0	22.0	3.4	16.8	4.5	3.7	60.1	-
Fuchs 2019 [37]	317	22 ± 18	1.49 ± 0.41	37.1	32.2	13.6	30.9	24.9	11.7	27.8	57.1
Krikščiūnienė. 2019 [38]	50	29.7 ± 8.2	-	66.0	16.0	4.0	32.0	-	-	100	100
Lee 2019 [39]	42	22.3 [18.8–28.2]	-	33.3	9.5	2.4	19.0	-	14.3	90.5	97.6
Mortensen 2019^a [40]	91	38.0 ± 10.5	1.49 ± 0.16	63.7	28.6	12.1	30.8	-	-	-	-
Thunström 2019 [41]	198	28.2 ± 11.3	-	45.5	26.7	12.7	10.2	3.4	1.02	62.6	89.9
Donadille 2020 [42]	204	25.6 [19.6–34.2]	1.5 (1.4–1.6)	40.1	22.8	8.1	4.6	5.1	6.1	75.0	90.8
Lin 2020 [43]	125	28.4 ± 15.6	1.4 ± 0.4	35.2	27.2	8.8	29.6	28.8	9.6	52.6	64
Yetman 2020 [44]	393	33.8 ± 13.0	-	49.9	39.9	13.7	38.2	-	-	-	-
Meccanici 2022^b [45]	89	34.4 [24.4–44.0]	1.64 ± 0.22	33.7	29.2	11.2	21.3	10.1	4.5	40.0	69.3
Pooled estimate (95%CI)		30.0 (27.6–32.4)	1.50 (1.47–1.54)	50.5 (42.3–58.7)	24.8 (19.5–30.1)	8.26 (5.07–11.5)	26.5 (17.5–35.4)	9.21 (4.61–13.8)	5.74 (3.16–8.31)	60.5 (41.9–79.1)	89.4 (94.2–94.6)
Studies reported		14	7	13	14	13	11	6	8	9	9
I^2 (%)		96.0	87.7	93.7	87.9	87.8	95.5	88.9	77.6	98.8	94.6

a,b = overlapping study population with study with corresponding letter.

“-“ = variable not reported. For numerical variables mean ± standard deviation or median and interquartile range or range are reported. Categorical variables are presented as percentages. For the pooled estimates, means are reported for numerical variables and percentages for categorical variables, both including their corresponding 95% confidence interval.

Studies by Mortensen et al. 2013 and 2019 were not included in pooling, as well as Meccanici et al. 2022. Studies of which only aortic dissection incidence was extracted were also not included in pooling: Price et al. 1986, Sybert 1998, Gravholt et al. 2006 and Fuchs et al. 2019.

IQR = interquartile range, BSA = body surface area, BAV = bicuspid aortic valve, CI = confidence interval, COA = aortic coarctation, HT and HL, hypertension/hyperlipidemia as defined in article and/or receiving antihypertensive treatment, DM = diabetes mellitus, GH = past or present growth hormone treatment with hormone supplementation, ERT = estrogen replacement therapy.

Figure 2. Forest plot of prevalence of aortic dilatation defined as an ASI > 20 mm/m2 in the ascending aorta. Heterogeneity as assessed by I² was 57.5%. CI = confidence interval, RE = random effects.

Figure 3. Forest plot of the incidence of aortic dissections per 100.000 person-years. Heterogeneity as assessed by I² was 73.1%. CI = confidence interval, RE = random effects.

Table 2. Pooled estimates of absolute and indexed aortic diameters, and aortic growth at the level of the aortic root, ascending, and descending aorta.

	Aortic root	Ascending aorta	Descending aorta
Absolute aortic diameter (mm)
Pooled estimate (95%CI) (mm)	27.2 (23.2–31.1)	27.3 (25.6–28.9)	19.5 (18.7–20.3)
Range included studies (mm)	19.4–30.0	23.9–29.0	17.8–21.0
Number of studies	6	8	5
Number of patients	758	1238	522
I^2 (%)	99.4	96.8	88.8
Indexed aortic diameter (mm/m2)
Pooled estimate (95%CI) (mm/m^2)	20.8 (15.4–26.3)	17.9 (17.0–18.8)	13.0 (12.8–13.2)
Range included studies (mm/m^2)	18.5–28.8	14.7–20.0	12.8–13.1
Number of studies	6	11	3
Number of patients	719	1743	383
I^2 (%)	99.9	95.8	0.00
Aortic growth (mm/year)
Pooled estimate (95%CI) (mm/year)	0.13 (−0.09–0.36)	0.19 (0.16–0.21)	0.07 (0.06–0.08)
Range included studies (mm/year)	0.00–0.32	0.14–0.20	0.07–0.07
Number of studies	3	3	2
Number of patients	311	405	168
I^2 (%)	98.5	69.1	0.00

ASI = aortic sized index; CI = confidence interval; I² = heterogeneity assessment

Table 3. Description of aortic dissection cases in included studies.

First author, year	Case	Age (y)	Karyotype	Aortic size	Dissection type	AV type	COA	HT	Mortality*	Other CHD	Additional morbidity
Price 1986 [27]	1	18	45,X	-	-	-	Yes	-	Yes	-	-
	2	29	45,X/46X,r(X)	Aortic arch dilatation	-	-	-	-	Yes	-	-
	3	38	45,X	-	-	-	-	-	Yes	-	-
	4	39	45,X	-	-	-	-	-	Yes	-	-
Sybert 1998 [28]	1	40	45,X	-	A	TAV	No	Yes	Yes	No	Obesity
	2	39	45,X	-	Rupture	-	-	-	No	-	Blunt trauma**
	3	‘Child’	-	-	B	-	Yes	-	Yes	COA repair	-
Gravholt 2006 [30]	1	27	45,X	-	-	BAV	No	No	Yes	Dextrocardia	No
	2	38	45,X	Aortic root dilatation	-	TAV	No	No	Yes	No	Pregnancy (1 year ago)
	3	51	45,X/46,X,r(X)	-	-	TAV	No	No	No	No	Hypothyreoisis
	4	19	45,X	-	-	BAV	No	No	No	No	No
	5	36	45,X	-	-	BAV	No	Yes	No	No	Hypothyreoisis
	6	20	45,X	-	-	BAV	No	Yes	No	Aortic valve stenosis, COA repair	No
	7	34	45,X	-	-	TAV	Yes	Yes	Yes	Hypoplastic aortic arch, COA repair	No
	8	18	45,X/46,XY	-	-	-	-	-	Yes	-	-
	9	29	45,X	-	-	TAV	Yes	-	Yes	COA repair	-
	10	28	45,X	-	-	-	-	No	Yes	-	-
	11	50	45,X/46,X,r(X)	-	-	TAV	-	Yes	No	Moderate aortic insufficiency	No
Matura 2007 [17]	N = 3	44–57	-	36.9–47.8 mm/26.1–30.6 mm/m^2	-	BAV (n = 2), TAV (n = 1)	-	-	-	Elongated transverse arch (n = 3)	-
Duijnhouwer 2019 [14]	1	44	45,X	65 mm/39.2 mm/m^2	A	BAV	Yes	Yes	Yes	-	-
	2	44	45,X	30 mm/18.4 mm/m^2	B	TAV	No	No	Yes	-	-
Fuchs 2019 [37]	N = 4	50	-	47–66 mm	A	-	-	-	Yes (2/4)	-	-
	N = 2	30	-	-	B	-	-	-	Yes (0/2)	-	-
Mortensen 2019 [40]	1	36	-	28 mm/15 mm/m^2	B	BAV	No	Yes	-	Elongated transverse arch	-
	2	50	-	40 mm/26 mm/m^2	A	BAV	No	No	-	-	-
Thunström 2019 [41]	N = 9	42 ± 20.5	45,X: 44.4% (4/9)	37 ± 5 mm/23 ± 3 mm/m^2	-	BAV (n = 4) TAV (n = 4) Unknown (n = 1)	Yes (n = 3) No (n = 6)	44.4% (4/9)	-	-	-
Donadille 2020 [42]	1	65	-	44 mm/30.13 mm/m^2	-	-	-	-	Yes	-	-
Yetman 2020 [44]	1	19	-	50 mm	A	BAV	Yes	Yes	-	COA repair	Obesity
	2	19	-	‘normal’	A	BAV	No	No	-	-	-
	3	21	-	-	B	BAV	No	No	-	Prior aortic replacement	Obesity
	4	23	-	34 mm	A	BAV	Yes	Yes	-	COA repair	Obesity
	5	28	-	36 mm	A***	BAV	Yes	Yes	-	COA repair	Obesity
	6	31	-	32 mm	A	TAV	No	No	-	-	Obesity
	7	40	-	-	B	BAV	No	No	-	Prior aortic replacement	-
	8	42	-	‘normal’	A	BAV	No	-	-	-	-
	9	47	-	34 mm	A	TAV	Yes	Yes	-	Residual COA	-
	10	48	-	‘normal’	A	TAV	No	No	-	-	No
	11	49	-	-	A***	BAV	Yes	Yes	-	COA repair, prior aortic replacement	-
	12	60	-	45 mm	A	TAV	No	Yes	-	Aberrant RSCA	Smoker
	13	66	-	-	A	TAV	No	Yes	-	-	Multi-vessel CAD, smoker
	14	66	-	66 mm	A	TAV	Yes	Yes	-	COA repair, prior aortic replacement	Renal transplant, smoker
	15	-	-	-	B	-	-	-	-	-	Blunt trauma**

Age, age at the moment of dissection in years; aortic size, the diameter or aortic size index of the ascending aorta, or if not available, the maximum aortic size; AV = aortic valve; BAV = bicuspid aortic valve; TAV = tricuspid aortic valve; COA = aortic coarctation; HT = hypertension; CHD = congenital heart disease

“-“ unknown or not reported in article. *Mortality at time of dissection if reported in the study pre-admission or in perioperative period. ** Case 2 of Sybert et al. blunt chest trauma, case 15 of Yetman et al. motor vehicle accident. ***Case 5 and 11 of Yetman et al.: dissection site at the aortic arch/left subclavian artery and aortic arch, respectively

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