Cardiac Amyloidosis in Aging African Americans

描述（来自申请的逐字描述）：如果与获得 不考虑护理，心血管疾病的死亡率增加， 非洲裔美国人相对于其他群体的增加是由于 一些疾病，对疾病的心脏反应有质的不同， 影响到所有种族群体， 充血性心力衰竭一种未确诊的，共存的，相对普遍的， 难治性心肌病是一种可能的部分解释。晚 非裔美国人中淀粉样心肌病发病率是 比高加索人。然而，它会导致充血性心力衰竭和心律失常， 这些特征是相对非特异性的， 总是显而易见的。地高辛和钙通道阻滞剂在以下患者中具有毒性： 因此，淀粉样蛋白治疗其他病因的伴随心脏病可 受到损害;此外，淀粉样心脏病的误诊可能会导致 可能有害的治疗不明淀粉样变性，在60岁以上的人， 可能导致充血性心力衰竭研究中观察到的一些不应性， 心力衰竭和较高的心血管发病率和死亡率， 非裔美国人 我们的建议是研究一种由基因决定的迟发性淀粉样变性 由于血清蛋白中122位的瓦尔被ILE取代 甲状腺素运载蛋白（TTR）。大约4%的非洲裔美国人是杂合子， 该等位基因在年龄增长后具有淀粉样蛋白沉积的绝对风险 60导致154，000名非洲裔美国人患有某种程度的心脏病 淀粉样变性在两项关于心血管风险的研究中， 在社区（ARIC和CFIS），与非洲裔美国人的组合队列， 5200，我们将检验淀粉样蛋白基因的杂合性 等位基因与心脏淀粉样变性的临床证据相关， 相关死亡率上升。我们还将评估等位基因在以下方面的作用： 通过确定其在一个队列中的患病率， 60岁以上的非裔美国退伍军人被认为患有心脏病， 尽管他们的提供者还没有将淀粉样变性视为一种特异性的 诊断.我们将描述晚发性心脏病的自然史， 非裔美国人的淀粉样变性，确定其在心血管发病率中的作用 和死亡率，并确定支持性的指导方针， 目前的治疗和具体的治疗时，可用的。

DESCRIPTION (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.