Relative to European Americans (EAs), African Americans (AAs) have higher rates of myocardial infarction, possibly reflecting poorer access to healthcare. In contrast, when provided equal access to healthcare, AAs have 50% lower myocardial infarction rates than EAs. A related observation is that AAs have markedly less subclinical cardiovascular disease (CVD) measured as coronary artery calcified plaque (CAC). This occurs despite the presence of more severe conventional CVD risk factors in AAs. CAC predicts future risk of myocardial infarction. A paradigm shift developed based on our earlier finding that AAs are at lower biologic risk for developing CAC (and associated myocardial infarction) than EAs. Genetic polymorphisms exhibiting different frequencies between population groups likely contribute to the racial difference in CAC, as well as presence of novel CVD-associated factors including bone mineralization and serum vitamin D levels, both associated with CAC. This project targets the pathogenesis of CAC by focusing on racial differences in subclinical CVD with emphasis on the understudied relationship between bone health, vitamin D, and CAC. AAs also manifest lower rates of osteoporosis despite lower vitamin D levels and ingestion of less dietary calcium than EAs. There remains a critical need to collect longitudinal data tracking changes in CAC and bone mineral density in relation to vitamin D and assess the importance of these factors in AAs who are at high CVD risk. This renewal application proposes to: (1) longitudinally measure CAC and bone mineral density, and their relative association with novel CVD-associated factors including serum vitamin D and bone metabolism in African American-Diabetes Heart Study (AA-DHS) participants, among the most extensively phenotyped AA cohort with type 2 diabetes~ (2) explore the roles of novel CVD risk factors on development and progression of CAC~ and (3) identify the genetic variation that contributes to lower rates of CAC in AAs. The presence of diabetes in our unique AA-DHS cohort likely contributed to their higher CAC scores. Follow-up exams in the well phenotyped and genotyped AA-DHS cohort will provide critically important data which will increase our understanding of CVD risk in AAs. Our diabetes-duration matched sample of 1,200 EAs recruited in the Wake Forest Diabetes Heart Study with genome-wide association data will allow for rapid replication of genetic associations with CAC in AAs. The roles of vitamin D and bone metabolism on development and progression of CAC are of intense interest, as controversy surrounds supplemental vitamin D in AAs due to potential injury to coronary arteries and bone. Exploring links between genetic risk, bone health and vitamin D will improve our understanding of subclinical atherosclerosis in AAs and aid in development of novel treatment and prevention strategies.

Public Health Relevance

Epidemiological studies in more than 600,000 Kaiser Permanente and Veterans Administration patients reveal that African Americans with access to adequate healthcare are at lower risk for myocardial infarction than European Americans, an observation supported by population-based and clinical studies revealing substantially less coronary artery calcified plaque (CAC), also known as subclinical cardiovascular disease, in African Americans. Racial differences in the frequencies of genetic risk variants for coronary artery disease and novel cardiovascular disease risk factors including serum vitamin D levels and bone mineral density appear to be associated with the lower biologic risk of myocardial infarction and CAC in African Americans. This renewal application of RO1 DK071891 proposes to collect critically necessary date involving longitudinal change in CAC, bone mineral density, and serum vitamin D levels, and perform genetic analyses in African Americans at high risk for myocardial infarction to detect novel factors associated with susceptibility to (and protection) from CAC that can be applied to members of other race groups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK071891-07
Application #
8690833
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Malozowski, Saul N
Project Start
2005-07-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Palmer Allred, Nicholette D; Raffield, Laura M; Hardy, Joycelyn C et al. (2016) APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND. Diabetes Care 39:2225-2231
Hsu, Fang-Chi; Yuan, Mingxia; Bowden, Donald W et al. (2016) Adiposity is inversely associated with hippocampal volume in African Americans and European Americans with diabetes. J Diabetes Complications 30:1506-1512
Ma, Jun; Guan, Meijian; Bowden, Donald W et al. (2016) Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans. Clin J Am Soc Nephrol 11:1034-43
Yuan, Mingxia; Hsu, Fang-Chi; Bowden, Donald W et al. (2016) Relationships between measures of adiposity with subclinical atherosclerosis in patients with type 2 diabetes. Obesity (Silver Spring) 24:1810-8
Freedman, Barry I; Gadegbeku, Crystal A; Bryan, R Nick et al. (2016) APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume. Kidney Int 90:440-9
Wagenknecht, Lynne E; Divers, Jasmin; Register, Thomas C et al. (2016) Bone Mineral Density and Progression of Subclinical Atherosclerosis in African-Americans With Type 2 Diabetes. J Clin Endocrinol Metab 101:4135-4141
Palmer, Nicholette D; Divers, Jasmin; Lu, Lingyi et al. (2016) Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American-Diabetes Heart Study. Bone 87:71-7
Bonomo, Jason A; Palmer, Nicholette D; He, John Cijiang et al. (2015) Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease. Am J Nephrol 42:259-64
Hawkins, Gregory A; Friedman, David J; Lu, Lingyi et al. (2015) Re-Sequencing of the APOL1-APOL4 and MYH9 Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression. Am J Nephrol 42:99-106
Freedman, Barry I; Langefeld, Carl D; Lu, Lingyi et al. (2015) APOL1 associations with nephropathy, atherosclerosis, and all-cause mortality in African Americans with type 2 diabetes. Kidney Int 87:176-81

Showing the most recent 10 out of 57 publications