Effects of coagulation factor VII polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and maintenance phases of warfarin therapy

Figures & data

Table 1 Demographics and clinical characteristics of 207 cardiovascular patients treated with warfarin at the Queen Alia Heart Institute

Category	Subcategory	Poor metabolizers	Good metabolizers	Extensive metabolizers	P-valuea
Demographics	Patients, n (%)	31/207 (15%)	144/207 (69.5%)	32/207 (15.5%)
	Ageb [years]	56.61 [17.10]	54.74 [14.96]	47.22 [14.74]	0.019
	BMIb	28.2 [3.76]	27.85 [4.88]	27.57 [3.5]	0.830
	Smoking, n (%)	3/31 (9.7%)	27/144 (18.75%)	13/32 (40.62%)	<0.0001
	Male	58.1%	51.4%	65.6%	0.235
	Female	41.9%	48.6%	34.4%
Concomitant disease	Comorbidity	64.5%	68.1%	53.1%	0.080
	Hypertension	38.7%	41.7%	18.8%	0.053
	Diabetes mellitus	24%	21.5%	28%	0.960
	CHD	32.3%	26.4%	28.1%	0.800
	Thyroid	0%	3.5%	3.1%	0.577
	Lipid	3.2%	6.3%	3.1%	0.662
Medication	Aspirin	61.3%	66%	75%	0.488
Indication of treatment	MVR	19.1%	13.2%	21.9%	0.255
	AVR	6.5%	22.9%	21.9%
	AF	35.5%	18.1%	18.7%
	DVR	19.1%	22.9%	25.0%
	Others	19.2%	22.9%	12.5%
Target INR	2–3	45.2%	39.6%	37.5%	0.804
	2.5–3.5	54.8%	60.4%	62.5%
Mean weakly doseb		16.7 [2.85]	36.0 [7.41]	68.27 [43.68]	<0.0001
Mean INRb		2.8 [0.74]	2.38 [0.76]	2.46 [0.85]	0.021

Notes:

a P<0.05 is considered significant.

b Mean SD in square brackets.

Abbreviations: AF, atrial fibrillation; AVR, aortic valve replacement; BMI, body mass index; CHD, chronic heart disease; DVR, double valve replacement; INR, International Normalized Ratio; MVR, mitral valve replacement.

Table 2 Demographic characteristics of 210 controls

Category	Controls
Agea [years]	37.53 [13.95]
BMIa	26.74 [4.58]
Smoking, n (%)	67/210 (31.9%)
Male	114/210 (54.3%)
Female	96/210 (45.7%)

Note:

a Mean SD in square brackets.

Abbreviation: BMI, body mass index.

Table 3 Allele and genotype frequencies of the FVII polymorphisms in 210 controls and 207 Jordanian cardiovascular patients

Genotype	Patients (%)	Control (%)	P-valuea
H5H5	13/207 (6.3%)	0%	<0.0001
H6H6	94/207 (45.4%)	88/210 (42%)
H7H7	21/207 (10.1%)	27/210 (12.6%)
H8H8	2/207 (1%)	0%
H6H7	72/207 (34.8%)	90/210 (42.6%)
H5H6	5/207 (2.4%)	0%
H5H7	0%	2/210 (1.1%)
H6H8	0%	1/210 (0.6%)
H7H8	0%	2/210 (1.1%)
Allele
H5	31/414 (7.5%)	2/420 (0.6%)	<0.0001
H6	265/414 (64%)	267/420 (63.4%)
H7	114/414 (27.5%)	148/420 (35.2%)
H8	4/414 (1%)	3/420 (0.8%)

Note:

a Fisher’s exact test with P<0.05 is considered significant.

Table 4 Association of FVII polymorphism with warfarin sensitivity during the initiation phase of therapy of 207 cardiovascular patients

Gene	Genotype	Sensitive	Moderate	Resistance	P-valuea
FVII	H5H5	4/13 (30.8%)	8/13 (61.5%)	1/13 (7.7%)	0.192
	H6H6	18/94 (19.1%)	64/94 (68.1%)	12/94 (12.8%)
	H7H7	3/21 (14.3%)	16/21 (76.2%)	2/21 (9.5%)
	H8H8	0/2 (0.0%)	1/2 (50.0%)	1/2 (50.0%)
	H6H7	5/72 (7.0%)	52/72 (72.2%)	15/72 (20.8%)
	H5H6	1/5 (20.0%)	3/5 (60.0%)	1/5 (20.0%)

Note:

a Fisher’s exact test with P<0.05 is considered significant.

Table 5 Association of FVII polymorphism with warfarin sensitivity during the maintenance phase of therapy of 129 cardiovascular patients

Gene	Genotype	Sensitive	Moderate	Resistance	P-valuea
FVII	H5H5	1/6 (16.7%)	4/6 (66.6%)	1/6 (16.7%)	0.265
	H6H6	10/59 (17.0%)	36/59 (61.0%)	13/59 (22.0%)
	H7H7	2/14 (14.3%)	11/14 (78.6%)	1/14 (7.1%)
	H8H8	0/2 (0.0%)	0/2 (0.0%)	2/2 (100%)
	H6H7	4/45 (8.9%)	27/45 (60.0%)	14/45 (31.1%)
	H5H6	1/3 (33.3%)	2/3 (66.7%)	0/3 (0.0%)

Note:

a Fisher’s exact test with P<0.05 is considered significant.

Table 6 Association of FVII polymorphism with variability in the dose of warfarin required

Gene	Genotype	Initiation dose	95% CI		P-valuea	Maintenance dose	95% CI		P-valuea
			Lower bound	Upper bound			Lower bound	Upper bound
FVII	H5H5	34.6000	28.8449	40.3551	0.192	33.3500	21.3848	45.3152	0.555
	H6H6	35.4160	32.7885	38.0434		36.6237	32.2124	41.0350
	H7H7	35.7476	28.8805	42.6147		39.0714	25.6558	52.4870
	H8H8	45.8500	–6.8807	98.5807		51.9000	44.2763	59.5237
	H6H7	43.1903	35.0782	51.3024		42.0244	36.2852	47.7637
	H5H6	23.8200	9.6190	38.0210		34.5000	–10.6779	79.6779

Note:

a One-way ANOVA with P<0.05 is considered significant, mean doses.

Table 7 Association of FVII polymorphism with the response to warfarin during the initiation phase of therapy of 207 cardiovascular patients

Gene	Genotype	Poor responder	Good responder	Extensive responder	P-valuea
FVII	H5H5	4/13 (30.8%)	7/13 (53.8%)	2/13 (15.4%)	0.920
	H6H6	41/94 (43.6%)	44/94 (46.8%)	9/94 (9.6%)
	H7H7	9/21 (42.9%)	10/21 (47.6%)	2/21 (9.5%)
	H8H8	1/2 (50.0%)	1/2 (50.0%)	0/2 (0.0%)
	H6H7	29/72 (40.2%)	30/72 (41.7%)	13/72 (18.1%)
	H5H6	2/5 (40.0%)	2/5 (40.0%)	1/5 (20.0%)

Note:

a Fisher’s exact test with P<0.05 is considered significant.

Table 8 Association of FVII polymorphism with warfarin response during the maintenance phase of therapy of 129 cardiovascular patients

Gene	Genotype	Poor responder	Good responder	Extensive responder	P-valuea
FVII	H5H5	2/6 (33.3%)	4/6 (66.7%)	0/6 (0.0%)	0.296
	H6H6	3/59 (5.2%)	52/59 (87.9%)	4/59 (6.9%)
	H7H7	1/14 (7.1%)	13/14 (92.9%)	0/14 (0.0%)
	H8H8	0/2 (0.0%)	2/2 (100.0%)	0/2 (0.0%)
	H6H7	2/45 (4.4%)	41/45 (91.2%)	2/45 (4.4%)
	H5H6	1/3 (33.3%)	2/3 (66.7%)	0/3 (0.0%)

Note:

a Fisher’s exact test with P<0.05 is considered significant.

Table 9 Association of FVII polymorphism with INR treatment outcome

Gene	Genotype	Initiation INR	95% CI		P-valuea	Maintenance INR	95% CI		P-valuea
			Lower bound	Upper bound			Lower bound	Upper bound
FVII	H5H5	2.5231	2.1028	2.9433	0.995	2.4333	2.1173	2.7493	0.012
	H6H6	2.4500	2.2846	2.6154		2.7393	2.6511	2.8275
	H7H7	2.4952	2.1364	2.8541		2.8143	2.5891	3.0395
	H8H8	2.3000	1.0294	3.5706		2.5000	−.0412	5.0412
	H6H7	2.4521	2.2677	2.6365		2.6633	2.5347	2.7919
	H5H6	2.0200	1.3665	2.6735		2.0333	1.4082	2.6585

Note:

a One-way ANOVA with P<0.05 is considered significant, mean INR.

Abbreviation: INR, International Normalized Ratio.