(Verbatim from the application): If factors related to access to care are not considered, the increased mortality from cardiovascular disease in African-Americans relative to other groups is due to the increased frequency of some diseases, a qualitatively different cardiac response to disorders affecting all ethnic groups and a relatively poor response to treatment of congestive heart failure. An undiagnosed, coexistent, relatively prevalent, treatment-resistant cardiomyopathy is a possible partial explanation. Late onset amyloidotic cardiomyopathy is fourfold more common in African-Americans than Caucasians. It causes congestive heart failure and arrhythmias, however these features are relatively non-specific and the clinical diagnosis is not always obvious. Digoxin and calcium channel blockers are toxic in patients with amyloid, thus, treatment of concomitant heart disease of other etiologies may be compromised; moreover misdiagnosis of amyloid heart disease may result in possibly harmful therapy. Unrecognized amyloidosis, in individuals over age 60, could contribute to some of the refractoriness seen in studies of congestive heart failure and to the higher cardiovascular morbidity and mortality in African-Americans. Our proposal examines a genetically determined form of late-onset amyloidosis due to a substitution of ILE for VAL at position 122 in the serum protein transthyretin (TTR). Approximately 4% of African-Americans are heterozygous for the allele that has an absolute risk for anatomic amyloid deposition after age 60 resulting in 154,000 African-Americans with some degree of cardiac amyloidosis. In a collaborative effort with two studies of cardiovascular risk in the community (ARIC and CFIS), with a combined African-American cohort of 5200, we will test the hypothesis that heterozygosity for the amyloidogenic allele is associated with clinical evidence of cardiac amyloidosis and a related increase in mortality. We will also assess the role of the allele in clinical heart disease by determining its prevalence in a cohort of African-American veterans, over 60, who are recognized as having heart disease, although their providers have not considered amyloidosis as a specific diagnosis. We will characterize the natural history of late onset cardiac amyloidosis in African-Americans, define its role in cardiovascular morbidity and mortality in this ethnic group and define guidelines for supportive treatment at present and specific therapy when available.
Showing the most recent 10 out of 20 publications
