Blood pressure and total cholesterol level are critical risks especially for hemorrhagic stroke in Akita, Japan. Manabu Izumi, Kazuo Suzuki, Tetsuya Sakamoto and Masato Hayashi Jichi Medical University Research Institute for Brain and Blood vessels-akita
Background Stroke is one of the leading causes of death and disability in Akita, Japan, same as all over the world. Stroke prevention is considered one of the best strategies for improving public health. Hypertension, diabetes mellitus, hyperlipidemia, obesity, smoking, and drinking are well known as risk factors for stroke all over the world. While, differences of the distribution of risk factors exist in stroke subtypes, countries, and races. To prevent stroke in target populations, it is important to identify specific risk factors by stroke subtype, location, and race.
Purpose We performed a retrospective cohort study to assess risk factors for stroke depending on the subtypes in Akita, northern territory of Japan. Japanese World Map
Where is Akita? And what is characteristics of Akita? Weather ; (Summer is like Rome and winter is like Stockholm) Almost one race Japanese and health-insurance system that covers all of its citizens Stroke subtype; (Cerebral infarction; CI, Cerebral hemorrhage; CI and Subarachnoid hemorrhage; SAH) The rose line means latitude of 40 degrees north.
Characteristics of Akita Prefecture The climate in Akita is characteristically marked by long winters and short summers. we have a heavy fall of snow in winter. Akita Prefecture shares the same latitude with Beijing, Madrid and New York. Area Population Mortality of stroke 11,434 km2 5th in Japan 1,142,799 people 5th in Japan 1613 /million 1st in Japan Research Institute for Brain and Vessels-Akita, Specialist Hospital for Stroke
Methods: Mass health screening data was collected from the Akita Prefectural Federation of Agricultural Cooperative for Health and Welfare from 1991 to 1998. Cerebrovascular events were determined from the Akita stroke registry from 1991 to 2001. Then, clinical risk factors for stroke, such as hypertension, hyperlipidemia and diabetes mellitus, were assessed in the different subtypes of stroke. Disease classifications were made using the international Classification of ICD9 and classifications were follows: cerebral infarction (CI), cerebral hemorrhage (CH), and subarachnoid hemorrhage (SAH). The Akita stoke registry consisted of the basis of informed consent from all patients with stroke event who were admitted to a hospital and included all stroke events and stroke related deaths that required immediate hospitalization in all emergency medical facilities of Akita Prefecture.
Methods: A first-ever stroke occurring less than 3 years after the screening examination (i.e., from 1991 to 2001) was defined as a stroke event. As stroke risk factors, age, sex, history of DM, blood pressure (BP), serum total cholesterol (TC), body mass index (BMI), smoking, and drinking were assessed. Significant risk factors were detected by multivariable logistic regression analysis. Reductions in risk and 95% CI were estimated with use of the Cox proportional-hazards model. We also assessed interactions with a p value of <0.001 (two-sided test) being considered statistically significant.
Result: Table 1 Number of subject and stroke event by age and sex. Men Age(y.o.) Non stroke CH CI SAH Total 30-49 33435 27 27 23 33512 50-59 19460 56 82 25 19623 60-69 15482 72 178 33 15765 70-79 6156 47 145 8 6356 80-1026 15 33 0 1074 total 75559 217 465 89 76330 Women Age(y.o.) Non stroke CH CI SAH Total 30-49 30471 3 14 21 30509 50-59 20183 33 33 19 20268 60-69 20198 65 83 60 20406 70-79 8100 39 114 29 8282 80-1058 4 30 5 1097 Total 80010 144 274 134 80562
Result: Table 2 Age-specific stroke incidence /100,000 by sex Men Age(y.o.) CH CI SAH ALL 30-39 6.2 3.1 15.6 24.9 40-49 36.6 38 26.3 100.9 50-59 95.1 139.3 42.5 276.9 60-69 152.2 376.4 69.8 598.4 70-79 246.5 760.4 42 1048.9 80-465.5 1024.2-1489.8 Women Age CH CI SAH ALL 30-39 - 10.1 23.5 33.5 40-49 4.9 17.8 22.7 45.4 50-59 54.3 54.3 31.2 139.8 60-69 106.2 135.6 98 339.8 70-79 157 458.8 116.7 732.5 80-121.5 911.6 151.9 1185.1
Result: Table 3 Risk factors comparison by stroke event and sex Men Women Factors Non-stroke Stroke Non-stroke Stroke Mean (95% CI) Mean (95% CI) Mean (95% CI) Mean (95% CI) Age (years old) 53.1 (53.0, 53.2) 64.5 (63.7, 65.2) 54.8 (54.7, 54.9) 66.7 (65.8, 67.5) SBP (mmhg) 130.8 (130.6, 130.9) 144.7 (143.2, 146.1) 127.6 (127.4, 127.7) 145.5 (143.8, 147.1) DBP (mmhg) 80 ( 79.9, 80.1) 85.6 ( 84.7, 86.5) 76.1 ( 76.0, 76.2) 83.3 ( 82.4, 84.3) BMI 23.5 ( 23.4, 23.6) 23.3 ( 23.1, 23.5) 23.5 ( 23.4, 23.6) 24.1 ( 23.8, 24.4) TC (mg/dl) 197.4 (197.1, 197.6) 191 (188.5, 193.5) 205.3 (205.0, 205.5) 210.7 (207.6, 213.8) Drinking (number) No 63509 610 p<0.001 79430 545 p=0.129 Yes 12053 161 580 7 Smoking (number) No 60785 546 p<0.001 78518 543 p=0.761 1-10/day 2680 64 1002 5 11-20/day 8523 129 441 4 >=21 3571 32 49 0 DM (number) No 73833 737 p<0.001 78368 524 p<0.001 Yes 1726 34 1642 26 TC; Total Cholesterol, BMI; Body mass index, DM; Diabetes mullitus, SBP; Systolic BP and DBP; Diastolic BP
Relative risk of the risk factors of stroke subtypes by multi logistic regression analysis Factors Intracranial Brain Subarachnoid Total hemorrhage(95%ci) infarction(95%ci) hemorrhage(95%ci) Stroke(95%CI) Sex Male 1 1 1 1 Female 0.7( 0.6, 0.9) 0.6( 0.5, 0.7) 1.8( 1.3, 2.5) 0.7 (0.6, 0.8) Age 30-49yo 1 1 1 1 50-59 3.5( 2.3, 5.4) 4.0( 2.8, 5.8) 1.3( 0.8, 1.9) 2.9 (2.3, 3.6) 60-69 5.1( 3.4, 7.7) 9.4( 6.7,13.2) 2.4( 1.7, 3.5) 5.6 (4.6, 6.9) 70-79 7.1( 4.6,10.9) 22.5(16.0,31.6) 2.1( 1.3, 3.3) 10.1 (8.1,12.5) 80-89 9.4( 5.2,17.0) 36.4(24.3,54.7) 1.7( 0.7, 4.3) 14.7(11.0,19.6) Classification of BP Optimal 1 1 1 1 Normal 1.7( 0.9, 3.4) 1.4( 1.0, 1.9) 2.8( 1.5, 5.4) 1.6 (1.2, 2.1) Normal high 3.7( 2.0, 6.7) 1.8( 1.3, 2.4) 2.8( 1.5, 5.4) 2.2 (1.7, 2.9) Mild HT 6.6( 3.7,11.7) 2.2( 1.6, 2.9) 6.4( 3.5,11.5) 3.3 (2.6, 4.2) Medium HT 13.1( 7.2,23.7) 2.6( 1.9, 3.6) 10.0( 5.3,18.7) 4.9 (3.8, 6.3) Severe HT 24.9(13.2,46.9) 5.0( 3.4, 7.3) 16.1( 7.7,33.5) 9.1 (6.8,12.2)
Relative risk of the risk factors of stroke subtypes by multi logistic regression analysis Factors Intracranial Brain Subarachnoid Total hemorrhage(95%ci) infarction(95%ci) hemorrhage(95%ci) Stroke(95%CI) Body mass index less than 18.5 1.3( 0.8, 2.1) 0.6( 0.4, 0.9) 1.5( 0.9, 2.6) 0.9 (0.7, 1.2) 18.5-25 1 1 1 1 25-30 1.0( 0.8, 1.3) 1.2( 1.0, 1.4) 0.7( 0.5, 1.0) 1.0 (0.9, 1.2) more than 30 1.8( 1.2, 2.9) 1.1( 0.7, 1.7) 1.2( 0.6, 2.2) 1.3 (1.0, 1.8) Total cholesterol <160mg/dl 1 1 1 1 160-199 0.6( 0.5, 0.9) 0.9( 0.7, 1.1) 0.4( 0.3, 0.6) 0.7 (0.6, 0.8) 200-239 0.6( 0.4, 0.8) 0.9( 0.7, 1.2) 0.5( 0.4, 0.8) 0.7 (0.6, 0.9) 240-279 0.6( 0.4, 0.9) 0.9( 0.7, 1.2) 0.4( 0.2, 0.7) 0.9 (0.6, 1.4) >=280mg/dl 0.6( 0.3, 1.3) 1.7( 1.1, 2.6) 0.2( 0.0, 0.8) 0.9 (0.8, 1.1) Drinking No 1 1 1 1 Yes 1.2( 0.9, 1.7) 0.8( 0.7, 1.1) 1.0( 0.6, 1.7) 1.0 (0.8, 1.1) Smoking No 1 1 1 1 <10/day 0.9( 0.5, 1.6) 1.7( 1.3, 2.3) 1.5( 0.7, 3.1) 1.5 (1.1, 1.9) 11-20/day 1.0( 0.6, 1.5) 1.9( 1.5, 2.5) 1.3( 0.7, 2.3) 1.5 (1.3, 1.9) >=21 1.2( 0.6, 2.5) 1.5( 0.9, 2.5) 2.4( 1.1, 5.3) 1.5 (1.1, 2.2) Diabetes mellitus No 1 1 1 1 Yes 0.9( 0.5, 1.5) 1.6( 1.2, 2.1) 0.4( 0.1, 1.2) 1.2 (0.9, 1.6)
Relative risk Relative risk of the combinations with blood pressure and cholesterol against the lowest in hemorrhagic stroke 15 10 5 0 3.7 7.8 14.8 10.5 3.8 4.5 1.6 1.9 1.5 1.0 0.5 0.9 1.0 <160-200 -240 >240 Total cholesterol mg/dl 7.4 8.0 3.3 normal preht HT-1 HT-2 JNC7 classification of blood pressure
Discussion: Hypertension is the strongest risk factor for stroke, especially for hemorrhagic stroke. Our results support the idea that stroke incidence will be increased along with higher BP level. Interestingly, however, this phenomenon is observed not only among hypertensive categories but also within normal BP levels. Our register showed that 40% of all stroke events occurred in either mildly hypertensive cases who were not receiving any pharmacologic therapy or normal BP cases. Even though high BP is associated with high stroke risk, mildly high BP is still a risk factor for stroke. Therefore, we should put the eyes on the hidden or untreated normal high BP person for reducing stroke incident.
Discussion: Our data also suggest that TC <160 mg/dl is a risk factor for hemorrhagic stroke, whereas levels >280 mg/dl are a risk factor for CI. The reasons for this phenomenon seem to be related to the high incidence of CH and low incidence of CI in our study compared with Western countries. The interaction of BP and TC is an important factor for CH among Japanese subjects. Our study showed that the highest BP combined with the lowest TC level was the strongest risk factor for CH. Low TC contributed to the risk of CH across all BP levels. We could reveal the synergic effect on hemorrhagic stroke between low TC and hypertension.
Conclusion: Japanese subjects in this study showed a high proportion of hemorrhagic stroke. The relative risk of all stroke subtypes are increasing with higher blood pressure. Moreover, high blood pressure and low TC (<160 mg/dl) were the strongest risk factor for hemorrhagic stroke. Future studies are needed to determine if typical Japanese food consumption causes high blood pressure and low TC and is associated with the incidence of stroke.