{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:54:19Z","timestamp":1787018059035,"version":"build-2736575974"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,3,14]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In the United States and Canada, folic acid fortification of enriched grain products was fully implemented by 1998. The resulting population-wide reduction in blood homocysteine concentrations might be expected to reduce stroke mortality if high homocysteine levels are an independent risk factor for stroke.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In this population-based cohort study with quasi-experimental intervention, we used segmented log-linear regression to evaluate trends in stroke-related mortality before and after folic acid fortification in the United States and Canada and, as a comparison, during the same period in England and Wales, where fortification is not required. Average blood folate concentrations increased and homocysteine concentrations decreased in the United States after fortification. The ongoing decline in stroke mortality observed in the United States between 1990 and 1997 accelerated in 1998 to 2002 in nearly all population strata, with an overall change from \u22120.3% (95% CI, \u22120.7 to 0.08) to \u22122.9 (95% CI, \u22123.5 to \u22122.3) per year (\n                    <jats:italic>P<\/jats:italic>\n                    =0.0005). Sensitivity analyses indicate that changes in other major recognized risk factors are unlikely to account for the reduced number of stroke-related deaths in the United States. The fall in stroke mortality in Canada averaged \u22121.0% (95% CI, \u22121.4 to \u22120.6) per year from 1990 to 1997 and accelerated to \u22125.4% (95% CI, \u22126.0 to \u22124.7) per year in 1998 to 2002 (\n                    <jats:italic>P<\/jats:italic>\n                    \u22640.0001). In contrast, the decline in stroke mortality in England and Wales did not change significantly between 1990 and 2002.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The improvement in stroke mortality observed after folic acid fortification in the United States and Canada but not in England and Wales is consistent with the hypothesis that folic acid fortification helps to reduce deaths from stroke.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.105.570846","type":"journal-article","created":{"date-parts":[[2006,3,13]],"date-time":"2006-03-13T17:12:48Z","timestamp":1142269968000},"page":"1335-1343","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":274,"title":["Improvement in Stroke Mortality in Canada and the United States, 1990 to 2002"],"prefix":"10.1161","volume":"113","author":[{"given":"Quanhe","family":"Yang","sequence":"first","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo D.","family":"Botto","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. David","family":"Erickson","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Berry","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Sambell","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Johansen","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.M.","family":"Friedman","sequence":"additional","affiliation":[{"name":"From the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Ga (Q.Y., J.D.E., R.J.B.); Department of Pediatrics, University of Utah, Salt Lake City (L.D.B.); Health Division, Statistics Canada, Ottawa, Ontario (C.S., H.J.); and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"8797","year":"1996","unstructured":"Food and Drug Administration. 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