Sudden and unexplained death in sleep (SUDS) is a leading cause of death of young men in several Asian populations. The immediate cause is ventricular fibrillation in the absence of known disease. A strong environmental component may be inferred from the regional nature of SUDS in groups that are culturally and genetically distinct and the rapid decline in rates of SUDS after migration of Southeast (SE) Asian refugees to the US. Risk of SUDS rises sharply to a peak among men aged 35 years of age, then declines with increasing age. In our pilot studies of SE Asian refugee men in Thailand with the highest known risk of SUDS we documented high-prevalences of prolonged heart rate corrected QT interval (QTc), thiamine deficiency, hypokalemia, and a positive association between poor thiamine status, measured by erythrocyte transketolase activity (ETK), and QTc. These limited studies were unable to precisely quantify the relationship between QTc and thiamine status, lacked sufficient power to examine the relationship between QTc and hypokalemia, did not include other electrolytes, and did not address the striking differences in risk of SUDS by sex and age. We propose a cross-sectional epidemiologic study of the determinants of QTc among 300 men and 300 woman in the population with the highest known risk of SUDS: SE Asian refugees in Thailand. During a 14-month period, informed consent will be obtained from subjects selected in an age-stratified random sample of refugees scheduled for routine medical screening. Blood samples, 12-lead and 24-hour ECGs, and interview data will be collected to test the following hypotheses: (1) mean QTc is greater in men than women, (2) mean QTc is greater in men aged 30-39 years than in men younger or older; no similar relationship is expected among women, (3) QTc is positively correlated with poor thiamine status, measured by erythrocyte transketolase activity, (4-6) QTc is negatively correlated with serum levels of potassium, magnesium, and total calcium, and (7) QTc is associated with abnormalities of autonomic control of the heart, as indicated by power spectral analysis of heart rate variability. Secondary aims include study of interactions of thiamine status and electrolytes in the prolongation of QTc, dynamic analysis of QT variation by heart rate level in 24-hr ECGs, and collection of blood specimens for later genetic studies. This study may lead to public health measures that reduce the burden of sudden death in sleep in SE Asian populations. Its broader scientific importance is the potential description of new models of environmentally induced prolonged QT interval, autonomic dysfunction, and risk of sudden death in sleep.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL049432-01
Application #
3368551
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1993-02-01
Project End
1994-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Munger, R G; Booton, E A (1998) Bangungut in Manila: sudden and unexplained death in sleep of adult Filipinos. Int J Epidemiol 27:677-84