leptin and Vascular-Calcification

Severe abdominal aortic calcification (AAC) points to high cardiovascular risk and leptin stimulates arterial calcification; however, clinical data on their association are scarce. We studied the link between serum leptin and AAC severity and progression, and the effect of smoking and lipid levels, on this association in men. Methods and Results: At baseline, 548 community-dwelling men aged 50-85 years underwent blood collection and lateral lumbar spine radiography. In 448 men, X-ray was repeated after 3 and 7.5 years. AAC was assessed using Kauppila's semiquantitative score. In multivariable models, high leptin was associated with higher odds of severe AAC (odds ratio [OR]=1.71 per SD, 95% confidence interval [CI]: 1.22-2.40). The odds of severe AAC were the highest in men who had elevated leptin levels and either were ever-smokers (OR=9.22, 95% CI: 3.43-24.78) or had hypertriglyceridemia (vs. men without these characteristics). Higher leptin was associated with greater AAC progression (OR=1.34 per SD, 95% CI: 1.04-1.74). The risk of AAC progression was the highest in men who had elevated leptin levels and either were current smokers or had high low-density lipoprotein-cholesterol levels (OR=5.91, 95% CI: 2.46-14.16 vs. men without these characteristics). These links remained significant after adjustment for baseline AAC and in subgroups defined according to smoking and low-density lipoprotein-cholesterol levels.. In older men, high leptin levels are associated with greater severity and rapid progression of AAC independent of smoking, low-density lipoprotein-cholesterol or triglycerides.

Topics: Age Factors; Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Diseases; Humans; Leptin; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Vascular Calcification

Adipokines have been associated with increased risk of cardiovascular disease. Our aim was to determine if adipokine levels are associated with coronary artery calcification (CAC) as well as all-cause mortality in incident dialysis patients.. In patients new to dialysis, we prospectively investigated the association of adiponectin, leptin and resistin with coronary artery calcification measured by ECG-gated computer tomography. Participants were recruited a median of two months after starting dialysis.. The mean age was 50.0 (12.6) years and 31.1% were women. About 42% percent had BMI > 30. Higher adiponectin levels were inversely associated with CAC progression as change in Agatston score [-155.1 (-267.9, -42.2), p = 0.008] or change in CAC volumes between scans [-2.8 (-4.9, -0.6), p = 0.01]. Higher leptin levels were associated with CAC progression [110.4 (34.3-186.6), p = 0.005]. Decreased leptin [HR 0.5 (0.3-0.9), p = 0.05] was associated with all-cause mortality in adjusted models. There was no significant association between all-cause mortality and adiponectin [1.4 (0.6-3.4), p = 0.4] or resistin [HR 1.7 (0.5-5.0), p = 0.4].. High adiponectin protects against CAC progression, but is not associated with increased all-cause mortality. Higher leptin, as well as higher leptin to adiponectin ratio, is associated with CAC progression. Lower leptin levels were associated with all-cause mortality. The association of adipokines and cardiovascular disease in individuals on dialysis is complex and requires further study.

Topics: Adipokines; Adiponectin; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Leptin; Male; Middle Aged; Renal Dialysis; Resistin; Risk Factors; Vascular Calcification

Mediastinal fat has been suggested to be associated with cardiovascular diseases such as carotid stiffness, atherosclerosis and coronary artery calcification. We investigated the possible role of Ad-36-induced obesity in the pathogenesis of the coronary artery disease (CAD). Ad-36 DNA was investigated in the anterior mediastinal fat tissue samples of obese adults with CAD. Seventy-five obese adults with left main coronary artery (LMCA) disease, 28 non-obese adults with valvular heart diseases, and 48 healthy individuals without cardiovascular problems were included as the obese patient group (OPG), non-obese patient group (NOG) and healthy control group (HCG), respectively. We also simultaneously investigated Ad-36 antibodies by serum neutralization test (SNA), and measured leptin and adinopectin levels. Ad-36 antibodies were detected only in 10 patients (13.3%) within the 75 OPG. A statistically significant difference was detected between OPG, NOG and HCG in terms of Ad-36 antibody positivity (p>0.05). Ad-36 DNA was not detected in mediastinal tissue samples of OPG and NOP without PCR inhibitors. We suggest that Ad-36 may not have an affinity for mediastinal adipose tissue in obese patients with left main CAD and valvular heart diseases. Ad-36 antibody positivity results are not sufficient to reach a causal relationship.

Topics: Adenoviruses, Human; Adipogenesis; Adiponectin; Adipose Tissue; Adult; Antibodies, Viral; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; DNA, Viral; Female; Heart Valve Diseases; Humans; Leptin; Male; Mediastinum; Middle Aged; Obesity; Vascular Calcification; Waist-Hip Ratio

Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA.. We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC.. Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men (p < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE.. IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Asian People; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Tumor Necrosis Factor-alpha; United States; Vascular Calcification

The negative relation of serum adiponectin to atherosclerosis becomes a positive association in patients with chronic kidney disease (CKD). We conducted a small-scale cross-sectional observational study, in 101 Japanese male hemodialysis patients, to examine the relationship of serum adiponectin and leptin to abdominal aortic calcification (AAC). The presence of AAC was evaluated from simple X-ray radiographs of the left lateral abdomen. Serum adiponectin was significantly higher in AAC-positive patients [18.8 (13.0-28.1) μg/mL] than in AAC-negative patients [15.4 (8.9-22.8) μg/mL] (p = 0.03), whereas serum leptin did not differ significantly between the two groups. Multiple logistic regression analysis showed that log adiponectin, but not log leptin, was independently and significantly associated in a positive manner with AAC (odds ratio: 16.31, 95% confidence interval: 1.70-156.41, p = 0.02), after adjustment for age, body weight, percentage body fat, hemodialysis duration, prevalence of diabetes mellitus, and other risk factors. In conclusion, we found a positive and independent association of serum adiponectin with AAC in male hemodialysis patients, indicating that the reversed association between serum adiponectin and atherosclerosis in patients with CKD dose not result from increased serum adiponectin due to the impaired urinary secretion.

Topics: Adiponectin; Aged; Aorta, Abdominal; Asian People; Cross-Sectional Studies; Humans; Leptin; Logistic Models; Male; Middle Aged; Radiography; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification

Adipokines are known to predict cardiovascular events, yet their association with coronary artery calcium (CAC), a surrogate marker of coronary atherosclerosis and risk factor for cardiovascular disease (CVD), is unclear. We aimed at assessing the association between adipokines and the severity and progression of CAC in healthy older adults, and at exploring potential modification by gender.. 409 men and women from the Rancho Bernardo Study with no known CVD underwent a chest computed tomography scan to determine baseline CAC severity; 329 returned 4.5 years later for a repeat scan to evaluate CAC progression. Adipokines (IL-6, adiponectin, leptin, and TNF-α) were measured from baseline blood samples. Ordinal linear and logistic regression models were used to determine the association of each adipokine with baseline severity and future progression of CAC.. Adjusting for age and sex, IL-6 and leptin were associated with greater odds of increasing CAC severity (OR = 1.63, 95% CI 1.22-2.19; OR = 1.19, 95% CI 0.99-1.43, respectively, per SD). The association with IL-6 remained significant in models further adjusted for lifestyle, body size, CVD risk factors, and body fat distribution. Adiponectin was associated with CAC progression (OR = 0.68, 95% CI 0.51-0.92 in fully adjusted models). This was modified by sex, with protective effects seen for men (OR = 0.57, 95% CI 0.38-0.85), but not for women (OR = 0.93, 95% CI 0.67-1.32; p-for-interaction = 0.04).. IL-6 and leptin predicted greater CAC severity while adiponectin predicted lower odds of CAC progression. More research is needed to explore biological mechanisms, including differences by sex.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; California; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Disease Progression; Female; Humans; Interleukin-6; Leptin; Linear Models; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Risk Factors; Severity of Illness Index; Sex Factors; Time Factors; Tumor Necrosis Factor-alpha; Vascular Calcification

Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT).. Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples.. Circulating estradiol levels were associated with leptin (β = 0.131, p < 0.001), but not with adiponectin (p > 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, β = -0.138) and total body BMD (p = 0.009, β = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake.. The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC.

Topics: Adipokines; Adiponectin; Aged; Body Composition; Bone Density; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Estradiol; Female; Humans; Leptin; Osteoporosis, Postmenopausal; Postmenopause; Vascular Calcification

Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain.. We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient.. After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques.. In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.

Topics: Angina, Stable; Biomarkers; Cholesterol, HDL; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Humans; Inflammation Mediators; Interleukin-6; Leptin; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Risk Factors; Tomography, X-Ray Computed; Vascular Calcification