Circulating miR-34a and Bone Mineral Density of Brazilian Very-Old Adults.

The human aging is marked by several body changes, including in bone mineral density (BMD). Research shows that microRNAs are important modulators of bone metabolism. The present research aims to analyze the whole blood concentration of 10 selected microRNAs (miRs) and their association with absolute and relative scores of BMD in specific osseous site of Brazilian very-old adults. Forty noninstitutionalized and apparently healthy, very old (≥80 years) outpatients were eligible for research. Anthropometry, biochemistry, and densitometry measurements were performed along with coronary artery calcification (CAC) scores and tested across total circulating levels of microRNAs. As expected, the relative BMD scores for the lumbosacral region (L1 to S5) and for the femoral head and neck observed in the sample denote weakened bone architecture, compatible with prevalent osteopenia and osteoporosis. In this context, one single significant association was found, and negatively implicated the miR-34a-5p with both absolute (ß = -0.36, P=0.001 for BMD) and relative (ß = -0.43, P=0.001 for T-score) densitometry indexes of the femoral head (adjusted to sex and physical activity practice), but not with the other sites. No difference in total blood concentrations of the miRs was found according to CAC scores. Our findings indicate greater circulating levels for miR-34a-5p among very-old adults who display the lowest scores of BMD, being a finding consistent with a modest contribution of the miR (along with co-variables) to the mineralization of that site. Attesting clinical relevance of our findings demands forthcoming studies.

Lower bone mass is associated with subclinical atherosclerosis, endothelial dysfunction and carotid thickness in the very elderly.

BACKGROUND AND AIMS: Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. METHODS: We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. RESULTS: Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16-8.85); p = 0.024] and IMT categories [OR:2.97(1.11-7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36-70.39); p = 0.023]. CONCLUSIONS: This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.

Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians.

Several studies have revealed that traditional risk factors are less effective in predicting CVD risk in the elderly, suggesting the need to identify new biomarkers. Here, we evaluated the association between serum cholesterol efflux capacity (CEC), an atheroprotective property of HDL recently identified as a novel marker of CVD risk, and atherosclerotic burden in a cohort of very old, healthy individuals. Serum CEC values were not significantly correlated either with calcium score or with markers of vulnerable plaque, such as positive remodeling, hypodensity, spotty calcification, or napking-ring sign. In addition, no association was detected between CEC and telomere length, a marker of biological aging that has been linked to atherosclerosis extent. Interestingly, elderly subjects presented a remarkably higher CEC (+30.2%; P < 0.0001) compared with values obtained from a cohort of sex-matched, cardiovascular event-free, middle-aged individuals. In conclusion, serum CEC is not related to traditional risk factors in very old, cardiovascular event-free subjects, but has significantly higher values compared with a healthy, younger population. Whether this improved HDL functionality may represent a protective factor in CVD onset must be established in future studies.

Sarcopenia, but not excess weight or increased caloric intake, is associated with coronary subclinical atherosclerosis in the very elderly.

BACKGROUND AND AIMS: Excess weight is a widespread condition related to increased risk of coronary heart disease (CHD). Sarcopenia is a catabolic pathway common of the aging process and also associated with CHD. In the elderly, both changes occur concurrently and it remains unclear the relative contribution on CHD risk. We aimed to investigate whether sarcopenia, excess weight, or both are associated with subclinical atherosclerosis and/or endothelial dysfunction in very elderly individuals. METHODS: We performed a cross-sectional study of cohort enrolled individuals, aged 80 years or older (n = 208), who had never manifested cardiovascular diseases. Blood tests, medical and nutritional evaluations, cardiac computed tomography, flow-mediated dilation (FMD) and physical performance tests were obtained at the study admission. Odds ratio (OR) was calculated by multivariate regression models using coronary calcium score (CCS) categories and FMD as dependent variables. Adjustment for potential confounders was done. RESULTS: Muscle mass, but not fatty mass, was inversely associated with CCS categories [OR:2.54(1.06-6.06); p = 0.018]. The lowering of gait speed was negatively related to CCS>100 [OR:2.36 (1.10-5.06); p = 0.028] and skeletal muscle index was directly associated with FMD [OR:5.44 (1.22-24.24); p = 0.026]. Total caloric intake was positively related to fatty mass [OR:2.71 (1.09-6.72); p = 0.031], but was not related to CCS. CONCLUSIONS: This study reveals that sarcopenia - comprised by reduction of muscle mass and its strength - is associated with subclinical atherosclerosis and endothelial dysfunction. Surprisingly, the excess of fatty mass seems not to be related to atherosclerotic burden in very elderly individuals.

ST-elevation myocardial infarction risk in the very elderly.

BACKGROUND: Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in < 24 h. METHODS: We enrolled participants aged 80 years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable. RESULTS: Low glomerular filtration rate (GFR) [OR:4.41 (1.78-10.95); p = 0.001], reduced levels of HDL-C [OR:10.70 (3.88-29.46); p = 0.001], male gender [OR:12.08 (5.82-25.08); p = 0.001], moderate to severe depressive symptoms [OR:10.00 (2.82-35.50); p = 0.001], prior smoking [OR:2.00 (1.05-3.80); p = 0.034] and current smoking [OR:6.58 (1.99-21.70); p = 0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C. CONCLUSIONS: This is the first case-control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group. GENERAL SIGNIFICANCE: In Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.

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.

Elevated serum uric acid is associated with vascular inflammation but not coronary artery calcification in the healthy octogenarians: the Brazilian study on healthy aging.

BACKGROUND: There is a limited data on the association between serum uric acid (SUA) and cardiovascular disease (CVD) among the very elderly population. AIMS: We evaluated the association of SUA, highly sensitive C-reactive protein (hs-CRP, a marker of vascular and systemic inflammation), and coronary artery calcification (CAC, a marker of subclinical CVD) in a cohort of Brazilian octogenarians (≥80 years) free from known clinical CVD. METHODS: 208 individuals were included and evaluated for an association between increasing tertiles of SUA, elevated hs-CRP (>3 mg/dL), the presence and burden of CAC (CAC > 0 and CAC > 400). RESULTS: The median hs-CRP was 1.9 (IQR = 1.0-3.4) mg/L and mean SUA was 5.3 (±1.4) mg/dL. The overall prevalence of elevated hs-CRP (>3 mg/dL) was 31 %. A significant increase in the prevalence of hs-CRP was noted across the higher SUA tertiles (p < 0.001) with 3.4 times the odds of having elevated hs-CRP in the highest SUA tertile (3.40; CI = 1.27-9.08). No association was noted with either the CAC presence and/or CAC burden (CAC > 0 or CAC > 400) across the increasing SUA tertiles. DISCUSSION: In the healthy octogenarians, higher SUA levels are associated with vascular inflammation (hs-CRP) but not with coronary atherosclerosis (CAC); markers for the subclinical CVD.

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.

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.

Emergent cardiovascular risk factors in the very elderly.

An appreciable amount of evidence generated in the recent decades has changed the incidence and mortality of cardiovascular diseases dramatically. This advance has resulted in increased survival and, consequently, in a large new generation of very elderly individuals. In parallel, the aging of the population brought out a puzzle and a challenge for the next millennium. Despite the role of selective survival in attenuating the expression and impact of traditional risk factors, today's elderly still has a gradual increase in unstable plaque formation and, by this way, the incidence of acute cardiovascular events. Recent studies have indicated aging-related emergence of new potential modulators of atherogenesis such as cellular senescence, immunosenescence, the syndrome of frailty, sarcopenia and sirtuins. This review will focus on the most recent and relevant evidence regarding the impact of these new players on atherogenicity in the elderly.

Atherosclerotic disease in octogenarians: a challenge for science and clinical practice.

Besides the time of exposure to the traditional risk factors, new players take the lead in the modulation of atherogenesis in the very elderly, promoting a step increase in the incidence of cardiovascular events. Accordingly, atherosclerotic plaques become more abundant and portray more unstable features, such as increased inflammatory activity and reduction of smooth muscle cells in the very elderly. This new scenario is composed of new potential modulators of atherogenesis such as cellular senescence, immunosenescence, frailty syndrome, sarcopenia and sirtuins, and changes among the traditional cardiovascular risk factors which gain new attributes and new magnitudes of interaction with atherosclerotic disease. Consistent with this concept, mortality from atherosclerotic disease has shown a decrease in individuals younger than 60 years, but no change in incidence in individuals over the age of 60 years. In this review, we present the most recent and relevant pieces of evidence to the peculiarities of traditional cardiovascular risk factors and new aging-related potential modulators of atherosclerotic disease in very elderly.

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction.

OBJECTIVE: Enhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event. METHODS: Consecutive patients (n=372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up. RESULTS: The decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p<0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r=0.46; p<0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p<0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p<0.05). CONCLUSION: Excessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI.

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.