Sis that the increased risk of HS in migraineurs may be partly mediated by the link between RCVS and migraine. Hypertension is one of the most important risk factors for HS [20?2]. Migraine attacks can be accompanied by increased blood pressure [23], which may also increase the risk of developing HS [20]. Nevertheless, after controlling for the presence of hypertension and the use of antihypertensive medication, the adjusted HR (2.13, 95 CI, 1.71 ?2.67) of HS for migraine remained significant and was similiar to the crude HR (2.22, 95 CI, 1.78 ?2.77), suggesting that the Title Loaded From File association between migraine and HS 1531364 is likely to be independent of hypertension. In the present study, we found that migraineurs had a 23115181 higher risk of HS irrespective of the migraine subgroup (MA, MO, or MU) and that the HRs were similar among the three subgroups(Table 3). However, in the Women’s Health Study [8], MA, but not MO, was shown to be significantly related to an increased risk of HS (HR 2.25, 95 CI 1.11?4.54, P = 0.024). Further studies are required to investigate whether there is a difference in HS risk between migraine subtypes in different ethnic populations. Migraine is more prevalent in females, with an estimated female: male ratio of 2?:1 [1,2]. Data on the association between migraine and HS in men are very limited. We found that migraine was associated with an increased risk of developing HS in both women and men, as shown in Table 4. Moreover, both younger (,45 years) and older ( 45 years) migraineurs were at higher risk of HS (Table 4), which suggests that the association between migraine and HS is due to mechanisms that are independent of age-related vascular changes. Table 2 shows that chronic rheumatic heart disease was associated with an increased risk of HS. Patients with chronic rheumatic heart disease might receive anticoagulant prophylaxisTable 3. Crude and adjusted hazard ratios of hemorrhagic stroke during the two-year follow-up for the migraine subgroups.Migraine subgroups MA subgroup Occurrence of HS Yes, n ( ) No, n ( ) Crude hazard ratio (95 CI) Adjusted* hazard ratio (95 CI) N = 1834 10 (0.55) 1824 (99.45) 2.24 (1.19 ?4.22){ 2.22 (1.18 ?4.18){ MO subgroup N = 3683 18 (0.49) 3665 (99.51) 2.01 (1.25 ?3.25){ 1.74 (1.08 ?2.81){ MU subgroup N = 15408 85 (0.55) 15323 (99.45) 2.26 (1.77 ?2.90){ 2.22 (1.74 ?2.84){*Variables included in the multiple regression analyses were age, sex, hypertension (with and without medication), diabetes, hyperlipidemia, coronary heart disease, chronic rheumatic heart disease, other heart disease, and the use of anticoagulant medication. { P,0.05; {P,0.0001. Abbreviations: HS, hemorrhagic stroke; MA, migraine with aura; MO, migraine without aura; MU, uncategorized migraine. doi:10.1371/journal.pone.0055253.tMigraine and Risk of Hemorrhagic Title Loaded From File StrokeTable 4. Crude and adjusted hazard ratios of hemorrhagic stroke for the migraine and non-migraine groups, stratified by sex and age.Patient sex* Women Non-MG Occurrence of HS Yes, n ( ) No, n ( ) Crude hazard ratio (95 CI) Adjusted hazard ratio (95 CI) N = 72915 145 (0.20) 72770 (99.80) 1.00 1.00 MG N = 14583 59 (0.40) 14524 (99.60) 2.04 { (1.50?2.76) 1.95 { (1.44?2.64) Men Non-MG N = 31710 110 (0.35) 31600 (99.65) 1.00 1.00 MG N = 6342 54 (0.85) 6288 (99.15) 2.46 { (1.78?3.41) 2.38 { (1.72?3.30) Patient age{ ,45years Non-MG N = 61520 65 (0.11) 61455 (99.89) 1.00 1.00 MG N = 12304 37 (0.30) 12267 (99.70) 2.85 { (1.90?.27) 2.58 { (1.72?.88) . 45years = = Non-MG N =.Sis that the increased risk of HS in migraineurs may be partly mediated by the link between RCVS and migraine. Hypertension is one of the most important risk factors for HS [20?2]. Migraine attacks can be accompanied by increased blood pressure [23], which may also increase the risk of developing HS [20]. Nevertheless, after controlling for the presence of hypertension and the use of antihypertensive medication, the adjusted HR (2.13, 95 CI, 1.71 ?2.67) of HS for migraine remained significant and was similiar to the crude HR (2.22, 95 CI, 1.78 ?2.77), suggesting that the association between migraine and HS 1531364 is likely to be independent of hypertension. In the present study, we found that migraineurs had a 23115181 higher risk of HS irrespective of the migraine subgroup (MA, MO, or MU) and that the HRs were similar among the three subgroups(Table 3). However, in the Women’s Health Study [8], MA, but not MO, was shown to be significantly related to an increased risk of HS (HR 2.25, 95 CI 1.11?4.54, P = 0.024). Further studies are required to investigate whether there is a difference in HS risk between migraine subtypes in different ethnic populations. Migraine is more prevalent in females, with an estimated female: male ratio of 2?:1 [1,2]. Data on the association between migraine and HS in men are very limited. We found that migraine was associated with an increased risk of developing HS in both women and men, as shown in Table 4. Moreover, both younger (,45 years) and older ( 45 years) migraineurs were at higher risk of HS (Table 4), which suggests that the association between migraine and HS is due to mechanisms that are independent of age-related vascular changes. Table 2 shows that chronic rheumatic heart disease was associated with an increased risk of HS. Patients with chronic rheumatic heart disease might receive anticoagulant prophylaxisTable 3. Crude and adjusted hazard ratios of hemorrhagic stroke during the two-year follow-up for the migraine subgroups.Migraine subgroups MA subgroup Occurrence of HS Yes, n ( ) No, n ( ) Crude hazard ratio (95 CI) Adjusted* hazard ratio (95 CI) N = 1834 10 (0.55) 1824 (99.45) 2.24 (1.19 ?4.22){ 2.22 (1.18 ?4.18){ MO subgroup N = 3683 18 (0.49) 3665 (99.51) 2.01 (1.25 ?3.25){ 1.74 (1.08 ?2.81){ MU subgroup N = 15408 85 (0.55) 15323 (99.45) 2.26 (1.77 ?2.90){ 2.22 (1.74 ?2.84){*Variables included in the multiple regression analyses were age, sex, hypertension (with and without medication), diabetes, hyperlipidemia, coronary heart disease, chronic rheumatic heart disease, other heart disease, and the use of anticoagulant medication. { P,0.05; {P,0.0001. Abbreviations: HS, hemorrhagic stroke; MA, migraine with aura; MO, migraine without aura; MU, uncategorized migraine. doi:10.1371/journal.pone.0055253.tMigraine and Risk of Hemorrhagic StrokeTable 4. Crude and adjusted hazard ratios of hemorrhagic stroke for the migraine and non-migraine groups, stratified by sex and age.Patient sex* Women Non-MG Occurrence of HS Yes, n ( ) No, n ( ) Crude hazard ratio (95 CI) Adjusted hazard ratio (95 CI) N = 72915 145 (0.20) 72770 (99.80) 1.00 1.00 MG N = 14583 59 (0.40) 14524 (99.60) 2.04 { (1.50?2.76) 1.95 { (1.44?2.64) Men Non-MG N = 31710 110 (0.35) 31600 (99.65) 1.00 1.00 MG N = 6342 54 (0.85) 6288 (99.15) 2.46 { (1.78?3.41) 2.38 { (1.72?3.30) Patient age{ ,45years Non-MG N = 61520 65 (0.11) 61455 (99.89) 1.00 1.00 MG N = 12304 37 (0.30) 12267 (99.70) 2.85 { (1.90?.27) 2.58 { (1.72?.88) . 45years = = Non-MG N =.
