Enhancing the ‘real world’ prediction of cardiovascular events and major bleeding with the CHA₂DS₂-VASc and HAS-BLED scores using multiple biomarkers

Figures & data

Table 1. Patients characteristics.

	N = 1361
Demographic and clinical characteristics
Age, median (IQR), years	76 (71–81)
Male	665 (49%)
Hypertension	1118 (82%)
Diabetes mellitus	363 (27%)
History of stroke or TIA	256 (19%)
Coronary artery disease	254 (19%)
Heart failure	429 (31%)
Peripheral artery disease	100 (7%)
Renal impairment	143 (10%)
Hypercholesterolemia	443 (33%)
Previous bleeding episode	113 (8%)
Alcohol abuse	49 (4%)
Hepatic disease	18 (1%)
Cancer	105 (8%)
Current smoker	209 (15%)
MDRD-4, median (IQR), ml/min/1,73 m^2	71 (56–85)
TTR, median (IQR), %	80 (66–100)
Antiplatelet therapy	243 (18%)
Blood biomarkers, median (interquartile range)
vWF, IU/dl	190 (132–234)
hsIL6, pg/ml	3.7 (2.2–6.0)
hsTnT, pg/ml	11.9 (7.8–18.0)
NT-proBNP, pg/ml	614 (319–1039)
Risk stratification, median (interquartile range)
CHA2DS2-VASc score	4 (3–5)
HAS-BLED score	2 (2–3)
Outcomes
Follow-up, median (IQR), days	2375 (1566–2887)
Composite of adverse cardiovascular events (%/year)	274 (3.10%/year)
Stroke (%/year)	130 (1.47%/year)
Major bleeding (%/year)	250 (2.83%/year)
Death (%/year)	551 (6.23%/year)

CHA₂DS₂-VASc: congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled]-vascular disease, age 65–74 years and sex category [female]; HAS-BLED: hypertension, abnormal renal and liver function (1 point each), stroke, bleeding history or predisposition, labile INR, old age (≥65 years), and use of drugs and alcohol concomitantly (1 point each); hsIL6: high sensitivity interleukin-6; hsTnT: high sensitivity troponin T; MDRD: modification of diet in renal disease equation for the estimation of glomerular filtration rate; NT-proBNP: N-terminal fragment B-type natriuretic peptide; TTR: time in therapeutic range; vWF: von Willebrand factor.

Table 2. Additive value of adding von Willebrand factor, high sensitivity troponin T, N-terminal fragment B-type natriuretic peptide, high sensitivity interleukin-6, time in therapeutic range and modification of diet in renal disease equation for prognosis in AF (n = 1361).

	AUC (95% CI) without	AUC (95% CI) with	p value	IDI (%)	p value	NRI (%)	p value
CHA2DS2-VASc score
Cardiovascular events^a	0.63 (0.59-0.66)	0.65 (0.61-0.69)	.030	0.85	<.001	−2.82	<.001
Stroke	0.61 (0.56–0.66)	0.62 (0.58–0.67)	.370	0.40	<.001	−2.56	.005
Major bleeding	0.55 (0.51–0.58)	0.56 (0.53–0.60)	.130	1.21	.034	−0.26	.830
All-cause mortality	0.67 (0.64–0.69)	0.70 (0.67–0.73)	.003	3.62	<.001	−1.56	.091
HAS-BLED score
Cardiovascular events^a	0.60 (0.56–0.63)	0.64 (0.61-0.68)	.003	1.00	<.001	−5.60	.201
Stroke	0.61 (0.57–0.66)	0.63 (0.58–0.68)	.430	0.11	<.001	−7.19	.200
Major bleeding	0.60 (0.56–0.63)	0.60 (0.56–0.64)	.840	1.34	<.001	−6.62	.133
All-cause mortality	0.61 (0.57–0.63)	0.67 (0.64–0.69)	<.001	5.00	<.001	0.65	.858

AUC: area under the curve; CI: confidence interval; IDI: integrated discrimination improvement; NRI: net reclassification improvement.

^aThis represents the composite of adverse cardiovascular events (i.e. stroke/systemic embolism, acute coronary syndrome, acute heart failure and cardiac death).

Figure 1. Decision curve analyses for the original and modified CHA₂DS₂-VASc and HAS-BLED risk scores (adding von Willebrand factor, high sensitivity troponin, N-terminal fragment B-type natriuretic peptide, high sensitivity interleukin-6, time in therapeutic range and Modification of Diet in Renal Disease equation for the estimation of glomerular filtration rate). (a) Composite of adverse cardiovascular events. (b) Stroke. (c) All-cause mortality. (d) Major bleeding.