Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study.

BACKGROUND: Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia. AIM: We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals. DESIGN: 178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited. METHODS: Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE). RESULTS: The DD genotype for ACE was independently associated ( b = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07). CONCLUSION: Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia.

Clinical utility of biomarkers in premature atherosclerosis.

Atherosclerosis is a very complex procedure responsible for the development of coronary artery disease which is the leading cause of death in the civilized world. The obvious pandemic character of atherosclerosis augments the need to discover an ideal biomarker, which will be able to facilitate the clinical diagnosis of the atherosclerosis from the physicians especially in the early stages of the atherosclerotic process. Among the biomarkers that are already used there are classical ones, such as c-reactive protein, interleukins, tumour necrosis factor, apolipoproteins, fibrinogen, homocysteine, and novel promising ones such as lipoprotein-associated phospholipase, asymmetric dimethylarginine, myeloperoxidase, cathepsins and cystatin C. The possibility of combining circulating biomarkers with other methods such as non-invasive and invasive imaging is clinically attractive because this could contribute to the improved diagnosis and understanding of premature atherosclerosis pathogenesis.

Circulating endothelial progenitor cells as biomarkers for prediction of cardiovascular outcomes.

Experimental studies suggest that bone marrow-derived endothelial progenitor cells (EPCs) play an important role in the maintenance of endothelial integrity and hemostasis. The number of circulating EPC has been shown to be inversely correlated with cardiovascular risk factors and vascular function and to predict cardiovascular events independent of both traditional and non-traditional risk factors. Thus, EPCs provide a clinical advantage over the use of other biomarkers as their measurement is directly associated with endothelial function, and available evidence suggests that they are consistently and significantly associated with a spectrum of cardiovascular complications, such as acute coronary syndromes and coronary artery disease. However, many issues in the field of EPC isolation and identification, particularly in regards to the effective and unequivocal molecular characterization of these cells still remain unresolved. In addition, simple EPC counts do not adequately describe cardiovascular disease risk. This limitation is attributable to variation in the definition of EPCs, the number of existing cardiovascular risk factors in different patients as well as a difference in the interaction between EPCs and other hematopoietic progenitor, inflammatory cells or platelets.