Silent coronary artery disease in type 2 diabetes mellitus: the role of Lipoprotein(a), homocysteine and apo(a) polymorphism

BACKGROUND: There is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD) in diabetic patients. We investigated whether Lipoprotein(a), homocysteine and apolipoprotein(a) polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD) in diabetic patients. METHODS: 1,971 type 2 diabetic patients without clinical signs of cardiovascular diseases and with a negative history of CAD were consecutively evaluated. Among them, 179 patients showed electrocardiographic abnormalities suggestive of ischemia or previous asymptomatic myocardial infarction. These 179 patients were subjected to a non-invasive test for CAD (ECG stress testing and/or scintigraphy). Among patients with a highly positive stress testing (n = 19) or a positive scintigraphy (n = 74), 75 showed an angiographically documented CAD (CAD group). Seventy-five patients without CAD (NO CAD group) were matched by age, sex and duration of diabetes to CAD patients. In NO CAD patients an exercise ECG test, a 48-hour ambulatory ECG and a stress echocardiogram were negative for CAD. RESULTS: Lipoprotein(a) levels (22.0 ± 18.9 versus 16.0 ± 19.4 mg/dl; p < 0.05), homocysteine levels (13.6 ± 6.6 versus 11.4 ± 4.9 mmol/l; p < 0.05) and the percentage of subjects with at least one small apolipoprotein(a) isoform (70.7% versus 29.3%; p < 0.0001) were higher in CAD than NO CAD group. Logistic regression analysis showed that apolipoprotein(a) polymorphism (OR:8.65; 95%CI:3.05–24.55), microalbuminuria (OR:6.16; 95%CI:2.21–17.18), smoking (OR:2.53; 95%CI:1.05–6.08), HDL (OR:3.16; 95%CI:1.28–7.81), homocysteine (OR:2.25; 95%CI:1.14–4.43) and Lipoprotein(a) (OR:2.62; 95%CI:1.01–6.79) were independent predictors of asymptomatic CAD. CONCLUSIONS: The present investigation shows an independent association of Lipoprotein(a), homocysteine and apo(a) polymorphism with silent CAD. Other studies are needed to establish whether these parameters are suitable for CAD screening in diabetic patients

Integrated cardiovascular/respiratory control in type 1 diabetes evidences functional imbalance : Possible role of hypoxia

Background: Cardiovascular (baroreflex) and respiratory (chemoreflex) control mechanisms were studied separately in diabetes, but their reciprocal interaction (well known for diseases like heart failure) had never been comprehensively assessed. We hypothesized that prevalent autonomic neuropathy would depress both reflexes, whereas prevalent autonomic imbalance through sympathetic activation would depress the baroreflex but enhance the chemoreflexes. Methods: In 46 type-1 diabetic subjects (7.0 +/- 0.9 year duration) and 103 age-matched controls we measured the baroreflex (average of 7 methods), and the chemoreflexes, (hypercapnic: ventilation/carbon dioxide slope during hyperoxic progressive hypercapnia; hypoxic: ventilation/oxygen saturation slope during normocapnic progressive hypoxia). Autonomic dysfunction was evaluated by cardiovascular reflex tests. Results: Resting oxygen saturation and baroreflex sensitivity were reduced in the diabetic group, whereas the hypercapnic chemoreflex was significantly increased in the entire diabetic group. Despite lower oxygen saturation the hypoxic chemoreflex showed a trend toward a depression in the diabetic group. Conclusion: Cardio-respiratory control imbalance is a common finding in early type 1 diabetes. A reduced sensitivity to hypoxia seems a primary factor leading to reflex sympathetic activation (enhanced hypercapnic chemoreflex and baroreflex depression), hence suggesting a functional origin of cardio-respiratory control imbalance in initial diabetes. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Erectile dysfunction and angiographic extent of coronary artery disease in type II diabetic patients

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Erectile Dysfunction as a Predictor of Cardiovascular Events and Death in Diabetic Patients With Angiographically Proven Asymptomatic Coronary Artery Disease A Potential Protective Role for Statins and 5-Phosphodiesterase Inhibitors

ObjectivesWe sought to investigate whether erectile dysfunction (ED) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease (CAD) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED.BackgroundCase-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available.MethodsType 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire.ResultsDuring a follow-up period of 47.2 ± 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p = 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p < 0.001). Among patients with CAD and ED, the Kaplan-Meier method showed that the statin (Mantel log-rank test: 3.921; p = 0.048) and 5-phosphodiesterase (5-PDE) inhibitor use (Mantel log-rank test: 4.608; p = 0.032) were associated with a lower rate of MACE. Cox regression analysis showed that statin use (HR 0.66; 95% CI 0.46 to 0.97; p = 0.036) reduced MACE. Treatment with 5-PDE inhibitors did not enter the model, but its p value was very near to the significant level (HR 0.68; 95% CI 0.46 to 1.01; p = 0.056).ConclusionsOur data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED

Evaluation of circulating sRAGE in osteoporosisaccording to BMI, adipokines and fracture risk: a pilot observational study

Background: Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. Results: Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. Conclusions: The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis

Relationship between apolipoprotein(a) size polymorphism and coronary heart disease in overweight subjects

BACKGROUND: Overweight is associated with an increased cardiovascular risk which is only partially explained by conventional risk factors. The objective of this study was to evaluate lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to coronary heart disease (CHD) in overweight subjects. METHODS: A total of 275 overweight (BMI ≥ 27 kg/m(2)) subjects, of which 155 had experienced a CHD event, 337 normal weight subjects with prior CHD and 103 CHD-free normal weight subjects were enrolled in the study. Lp(a) levels were determined by an ELISA technique and apo(a) isoforms were detected by a high-resolution immunoblotting method. RESULTS: Lp(a) levels were similar in the three study groups. Overweight subjects with CHD had Lp(a) concentrations significantly higher than those without [median (interquartile range): 20 (5–50.3) versus 12.6 (2.6–38.6) mg/dl, P < 0.05]. Furthermore, overweight subjects with CHD showed a higher prevalence of low molecular weight apo(a) isoforms than those without (55.5% versus 40.8%, P < 0.05) and with respect to the control group (55.5% versus 39.8%, P < 0.05). Stepwise regression analysis showed that apo(a) phenotypes, but not Lp(a) levels, entered the model as significant independent predictors of CHD in overweight subjects. CONCLUSIONS: Our data indicate that small-sized apo(a) isoforms are associated with CHD in overweight subjects. The characterization of apo(a) phenotypes might serve as a reliable biomarker to better assess the overall CHD risk of each subject with elevated BMI, leading to more intensive treatment of modifiable cardiovascular risk factors

Correlation between HIV disease and lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan

Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However, interpreting the impact of HIV infection on lipid metabolism is difficult because of various associated factors, including antiretroviral drugs and demographic characteristics. A few studies have associated HIV infection with lipid metabolism in antiretroviral-naïve HIV-infected patients. Because there were no data in this regard from Japan, the present study examined the impact of HIV infection, as well as demographic and clinical features, on lipid metabolism in antiretroviral-naïve HIV-infected patients in Japan. We performed a cross-sectional study to examine the impact of HIV disease, demographic and clinical characteristics on lipid metabolism among 168 HIV-infected Japanese men who were antiretroviral naïve and who did not have hemophilia, including patients who took medication for dyslipidemia. The mean age of the patients was 45.7 years; 0.6% of the patients took medication to dyslipidemia. The mean CD4 lymphocyte count was 289/μL, the mean baseline log10 HIV viral load was 4.2 HIV-1 RNA copies/mL, and 22% of the patients had a history of AIDS-defining events. A higher HDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.043). Also, a higher LDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.003). Infection with HIV was associated with dyslipidemia in antiretroviral-naïve patients. More advanced HIV disease was associated with less favorable lipid homeostatic profiles. These results are similar to findings from other countries

Soluble RAGE Plasma Levels in Patients with Coronary Artery Disease and Peripheral Artery Disease

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE

Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening

<p>Abstract</p> <p>Background</p> <p>Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care.</p> <p>Methods</p> <p>DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented.</p> <p>Results</p> <p>The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint.</p> <p>Conclusions</p> <p>These results suggest that the systematic detection of silent ischemia in high-risk asymptomatic patients with diabetes is unlikely to provide any major benefit on hard outcomes in patients whose cardiovascular risk is controlled by an optimal medical treatment.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00627783">NCT00627783</a></p