Atheroprotective Properties of Serum IGF-1 in the Carotid and Coronary Territories and Beneficial Role on the Physical Fitness of the Oldest Old.

Our aim was to investigate whether physiological levels of soluble insulin-like growth factor-1 (IGF-1) associate with coronary and carotid atherosclerotic burden and physical fitness in the oldest old by means of a cross-sectional study including 100 community-dwelling individuals with no previous cardiovascular events. Linear correlation was found between IGF-1 and intima-media thickness, number of carotid plaques, and walking speed. Individuals in the upper IGF-1 tertile had smaller right and left intima-media thickness compared with the intermediate and lower tertiles, along with reduced atherosclerotic plaques. Also, walking speed was greater in the upper IGF-1 tertile. On the other hand, a nonlinear correlation was observed between IGF-1 and coronary calcification scores, with the intermediate IGF-1 tertile associated to the lowest scores of calcification and participants with lower circulating levels of IGF-1 showing higher frequency of high-risk morphology plaques. All in all, our report supports a territory-dependent, atherorefractory phenotype in the oldest old carrying middle and/or higher serum levels of IGF-1.

Enhanced parathyroid hormone levels are associated with left ventricle hypertrophy in very elderly men and women.

Serum parathyroid hormone (PTH) has been found to be associated with cardiovascular mortality in the elderly, but little is known about the mechanisms underlying this association. This study investigated the association between PTH and structural and functional changes of the heart and arterial wall in a cohort of very elderly individuals. Healthy individuals aged 80 years or more (n = 90) underwent evaluation of serum PTH, cardiac morphology and function by Doppler echocardiography, endothelium dependent and independent vasodilatation by brachial reactivity, carotid stiffness and intima-media thickness by ultrasound, and coronary calcification by computed tomography. Participants with PTH levels above the median 5.8 pmol/L had higher left ventricular mass index (P = .02), relative wall thickness (P = .02), left atrial volume index (P = .03), and shorter deceleration time of E mitral wave (P = .04). Serum PTH levels (odds ratio, 1.027; P = .032) and systolic blood pressure (odds ratio, 1.032; P = .008) were independently associated with left ventricular hypertrophy. No difference was found between PTH groups in flow- or nitrate-mediated brachial artery dilatation, coronary artery calcification, intima-media thickness, or arterial stiffness. Elevation of serum PTH in the very elderly is associated with concentric left ventricular hypertrophy, but no association with arterial wall structure or function was found in this study.

Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians.

AIM OF THE STUDY: Although low-density lipoprotein cholesterol (LDL-C) has been consistently demonstrated a predictor of atherosclerotic disease in a large spectrum of clinical settings, among individuals aged of 80 years or older this concept is uncertain. This study was evaluated in a carefully selected population if the association between LDL-C and coronary atherosclerotic burden remains significant in the very elderly. METHODS: Individuals aged of 80 years or older (n = 208) who spontaneously sought primary prevention care and have never manifested cardiovascular disease, malnutrition, neoplastic or consumptive disease were enrolled for a cross-sectional analysis. Medical evaluation, anthropometric measurements, blood tests and cardiac computed tomography were obtained. RESULTS: In analyses adjusted for age, gender, diabetes, systolic and diastolic blood pressure, smoking and statin therapy, no association was found between coronary calcium score (CCS) and LDL-C [1.79 (0.75-4.29)]. There was no association between triglycerides and CCS. The association between high-density lipoprotein cholesterol (HDL-C) and CCS was significant and robust in unadjusted [0.32 (0.15-0.67)] as well as in the fully adjusted analysis [0.34 (0.15-0.75)]. CONCLUSION: The present study confirms in a healthy cohort of individuals aged of 80 years or more that while the association between LDL-C and coronary atherosclerosis weakens with aging, the opposite occurs with the levels of HDL-C.

Apoliprotein E genotype is associated with apoliprotein B plasma levels but not with coronary calcium score in very elderly individuals in primary care setting.

BACKGROUND: Epidemiological surveys indicate the influence of polymorphisms of apolipoprotein (apo) E on plasma lipids and triglyceride-rich lipoprotein levels, with impact on atherosclerotic phenotypes. AIM: We studied the association of classic genotypes of the apoE gene with clinical and biochemical risk factors for atherosclerosis in a segment of the very-old Brazilian individuals, with emphasis on the lipemic profile. METHODS: We performed cross-sectional analyses of clinical and laboratory assessments, including cardiac computed tomography, across ε2, ε3 and ε4 carriers of the apoE gene with a convenience sample of 208 participants eligible for prevention against cardiovascular events. RESULTS: When non-ε4 carriers were compared with ε4 carrying subjects, lower levels of ApoB as well as ApoB/ApoA ratios were observed in the former group. Tests between apoE polymorphisms with other clinical/biochemical variables and those with arterial calcification showed no significant differences between groups. CONCLUSION: The study suggests a possible atherogenic role of the ε4 allele attributable to increased ApoB levels and ApoB/ApoA ratios among very-old subjects in primary care setting.

C-reactive protein is independently associated with coronary atherosclerosis burden among octogenarians.

AIM OF THE STUDY: In contrast to the general population, individuals with primarily persistent elevation of inflammatory activity display a significant association between inflammatory biomarkers and atherosclerotic burden. In older individuals, immunosenescence upregulates the innate response and, by this way, may hypothetically favor the presence of this association. The aim of this study was to evaluate this hypothesis in healthy octogenarians. METHODS: Participants (n = 208) aged 80 years or older, asymptomatic and without medical and laboratory evidence of chronic diseases or use of anti-inflammatory treatments were included in the study. Lipid profile and plasma C-reactive protein (CRP) were measured at baseline and cardiac computed tomography was performed within 1-week interval for measuring coronary calcium score (CCS). RESULTS: The median plasma CRP was 1.9 mg/L (1.0­3.4) and 33 % of the participants had elevated CRP defined as C3 mg/L. Among those with high CRP, there was an increased frequency of high CCS (C100) as compared with their counterparts (71 vs 50 %, p = 0.001). The association between CRP and CCS persisted even after adjustment for age, sex, cardiovascular risk factors and statin therapy. The area under the receiver-operating curve for CRP was 0.606 using CCS C100 as a binary outcome. The sensitivities for CCS C100 were 40 and 74 % for the cutoff points of CRP C3 or 1 mg/L, respectively. CONCLUSION: The present study was able to confirm that in very elderly individuals, systemic inflammatory activity is independently associated with coronary atherosclerosis burden.

Low zinc levels is associated with increased inflammatory activity but not with atherosclerosis, arteriosclerosis or endothelial dysfunction among the very elderly.

BACKGROUND: Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall. METHODS: Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C-reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated. RESULTS: There was no significant difference in clinical or laboratorial data between subjects grouped according to plasma zinc tertile, except for CRP (p = 0.01) and blood leukocytes (p = 0.002), of which levels were higher in the upper tertiles. The average daily intake of zinc was not significantly correlated with zinc or CRP plasma levels. The plasma zinc/zinc intake ratio was inversely correlated with plasma CRP levels (- 0.18; p = 0.01). There was no significant difference between the plasma zinc tertiles and FMD, carotid intima-media thickness, coronary calcium score, carotid plaque presence, remodeled noncalcified coronary plaques, or low-attenuation noncalcified coronary plaques. CONCLUSION: Although plasma zinc level is inversely related to systemic inflammatory activity, its plasma levels of daily intake are not associated to alterations in structure or function of the arterial wall. GENERAL SIGNIFICANCE: In the very elderly plasma concentrations or daily intake of zinc is not related to endothelial dysfunction, arteriosclerosis or atherosclerotic burden at coronary or carotid arteries.

Osteopontin in bone mineral density of very old Brazilians.

Recent evidence suggests that changes in plasma levels of osteopontin (OPN) may be a promising marker for early diagnosis of bone disorders. We hypothesized that a frequent OPN gene polymorphism may be useful for identifying very old individuals with alterations in plasma OPN levels and consequently at risk of abnormal bone density scores. Men and women (80 years or older) living in the Brazilian Federal District underwent assessments with dual energy X-ray absorptiometry for bone mineral density (BMD) of the femoral neck, femoral head and lumbosacral (L1 to S5) regions. Clinical inspection was performed to assess other physical traits and to exclude co-morbidities (cardiovascular, autoimmunity, infections or neoplastic diseases). Serum concentrations of OPN were determined with an enzyme-linked immunosorbent assay, whereas the A7385G polymorphism (rs1126772) was determined by direct sequencing of a polymerase chain reaction product. Among the two hundred and ten subjects enrolled, no differential scores for bone mineral density could be observed across genotypes, but a greater content of circulating OPN was found among carriers of the A allele (P ≤ 0.05) even after adjustments. Serum OPN levels were negatively correlated with femoral neck density (P = 0.050 for BMD; P = 0.032 for T scores) but not with scores of the other regions investigated. Analyses with the sample dichotomized to age and body mass revealed that this inverse relationship was noticeable only among those aged within the highest and weighing within the lowest intervals. Our findings indicate elevated circulating osteopontin levels in patients with decreased bone mineral density, consistent with a modest contribution of an OPN allelic variation to its expression. Assessing the clinical relevance of our findings demands forthcoming studies.

Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly.

OBJECTIVE: To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and atherosclerotic burden at coronary and carotid arteries in individuals aged of 80 or more years old. METHODS: Healthy individuals aged between 80 and 102 years old (n = 178) underwent evaluation of plasma cytokines and acute phase proteins, intima-media thickness (IMT) and presence of plaques in carotid arteries by ultrasound and coronary artery calcification (CAC) by cardiac computed tomography. RESULTS: There was no association between CAC and carotid plaques (p = 0.8), maximum (p = 0.06) or mean IMT (p = 0.2). No association was found between the presence of carotid plaques and CRP (p = 0.4), TNF-α (p = 0.8) or IL-10 (p = 0.2). Likewise, individuals in the first three quartiles for CRP, TNF-α or IL-10 had similar values of CAC, mean and maximum IMT. In contrast, individuals above the 75th percentile for CRP or for TNF-α had enhanced maximum IMT (p = 0.017 and p < 0.0001) and CAC (p = 0.026 and p = 0.01) and subjects with IL-10 levels above the 75th percentile had lower maximum IMT (p = 0.027) and CAC (p = 0.006) as compared with those below this percentile. There was no difference in mean IMT for individuals above or below the 75th percentile for CRP, TNF-α or IL-10. CONCLUSION: In very old individuals, CAC and maximum IMT were positively associated with systemic inflammatory activity only in those above the 75th percentile. The markers of atherosclerotic burden at coronary and carotid arteries were not related to each other and were distinctly associated with pro- and anti-inflammatory mediators, suggesting that atherosclerosis development is different in these vascular beds.

Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography.

Visceral abdominal fat has been associated to cardiovascular risk factors and coronary artery disease (CAD). Computed tomography (CT) coronary angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk stratification. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. We prospectively evaluated 125 consecutive subjects (57% men, age 56.0+/-12 years) referred to perform CT angiography. Clinical and laboratory variables were determined and CT angiography and abdominal CT were performed in a 64-slice scanner. CAD was defined as any plaque calcified or not detected by CT angiography. Visceral and subcutaneous adiposity areas were determined at different intervertebral levels. CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements (waist and hip circumferences and body mass index). Otherwise, CT visceral fat areas (VFA) were significantly related to CAD. VFA T12-L1 values > or =145cm(2) had an odds ratio of 2.85 (95% CI 1.30-6.26) and VFA L4-L5 > or =150cm(2) had a 2.87-fold (95% CI 1.31-6.30) CAD risk. The multivariate analysis determined age and VFA T12-L1 as the only independent variables associated to CAD. Visceral fat assessed by CT is an independent marker of CAD determined by CT angiography.