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Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice.

Diabetic foot ulcers (DFUs) and cardiac autonomic neuropathy (CAN) are severe complications of diabetes mellitus (DM). Both DFU and CAN are associated with increased risk of major cardiovascular events and mortality. Because of the clinical impact of both these conditions, it is important to establish what effect the presence of CAN has on DFU outcomes.This is a narrative review of original research articles identified through an electronic search of PubMed, Scopus, and Google scholar databases until June 2021 exploring CAN in individuals with DFUs. We explored prevalence, patient outcomes (DFU healing and amputation), and mortality.Evidence suggests that the prevalence of CAN is high, ranging from 43% to 66% among those with DFUs. The presence of CAN may also increase the odds of developing DFUs. A single-center, prospective, observational study has suggested that the presence of CAN significantly reduces DFU healing time. The impact on amputation is indeterminate, with conflicting reports from studies reporting either no or increased risk. On the basis of limited evidence, CAN may be associated with increased mortality in individuals with DFUs.The interplay between CAN and DFUs is poorly understood from current literature. Given the high prevalence of CAN in individuals with DFUs and the potential for suboptimal outcomes, further high-quality studies are required to determine future management approaches when both conditions coexist and to establish whether early CAN screening in individuals with diabetes at high risk of foot ulceration may ultimately improve their outlook.

Recent evidence has linked circadian rhythm dysregulation to an increased risk of metabolic disorders. This study explores a potential association between variation in genes regulating the endogenous circadian timing system (clock genes) and the risk of type 2 diabetes (T2D) in a sample of Greek elderly people.Variants within and upstream or downstream of PPARA, PPARD, CLOCK/TMEM165, PER1, PER2 and PER3 genes were genotyped in 716 individuals with T2D (A) and 569 normoglycemic controls (B), and allele frequencies were compared between the groups in a case control study design.Samples were genotyped on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. To avoid the possibility of subjects with prediabetes being included in the control group, people with HbA1c5.7% and fasting glucose100 mg/dl comprised group C (n = 393), for whom a separate analysis was performed (secondary analysis).A protective role against T2D was identified for 14 variants in the PPARA gene. The rs7291444, rs36125344, rs6008384 in PKDREJ, located upstream of PPARA, and rs2859389 in UTS2, located upstream of PER3, demonstrated a protective role against T2D in both analyses. In contrast, rs6744132, located between HES6 and PER2, was positively correlated with T2D risk. Only in the secondary analysis, rs2278637 in VAMP2, located downstream of PER1, and rs11943456 in CLOCK/TMEM165 were found to confer protection against T2D. In a recessive model analysis of all groups, PPARD variants exhibited a protective role against disease.Our findings suggest a possible implication of clock genes in T2D susceptibility. Further studies are needed to clarify the mechanisms that connect circadian rhythm dysfunction and T2D pathogenesis.

Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system. Keywords: Cardiovascular disease, Diabetes mellitus, Randomised controlled trials, Treatment

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

To examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM).We included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests.For DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %).In a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are oral antidiabetic agents that exert their glucose-lowering effect by increasing renal excretion of glucose. These drugs have been reported to beneficially affect cardiovascular (CV) and renal outcomes. However, concerns have recently been raised in relation to increased risk of lower-extremities amputation with canagliflozin and it remains unclear whether and to what extent this side effect could also occur with other SGLT2i. The present expert panel overview focuses on the three SGLT2i available and widely used in the US and Europe, i.e. empagliflozin, canagliflozin and dapagliflozin and only refers briefly to other SGLT2i for which less data are available. The results of large CV outcome trials with these SGLT2i are presented, focusing specifically on the data in relation to amputation risk. The potential pathophysiological mechanisms involved in this side effect are discussed. Furthermore, available data reporting amputation cases in SGLT2i users are critically reviewed. The expert panel concludes that, based on current data, increased amputation risk seems to be related only to canagliflozin, thus representing a drug-effect rather than a SGLT2i class-effect. The exact pathways underlying this drug-induced adverse event, possibly related to off-target drug effects rather than SGLT2 inhibition per se, should be elucidated in future studies. Continuous monitoring and pharmacovigilance is necessary and head to head trials would also be essential to provide definitive conclusions.

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger (p .001) and had lower median admission NIHSS-scores (p .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Lifestyle modification, including a healthy diet, is of paramount importance in the management of diabetes mellitus. To this end, diets have been proposed with low glycemic index (an index of carbohydrate food expressing how quickly this nutrient can increase blood glucose) and glycemic load (an index obtained by multiplying the glycemic index by the grams of carbohydrate, then dividing by 100). The aim of this review was to discuss the potential contribution of diets with low glycemic index and glycemic load in diabetic microvascular complications. Currently, their role to the prevention and delay of microvascular complications in diabetes mellitus remains unclear, and further knowledge is desirable.

Aims To evaluate two definitions of response and the predictive value of baseline covariates for response to actovegin treatment in type 2 diabetic patients with symptomatic diabetic sensorimotor polyneuropathy (DSPN). Methods Response to 6-months treatment with actovegin or placebo was defined as a clinically meaningful decline from baseline to 6 months in (1) both Neuropathy Impairment Score of Lower Limbs (NIS-LL) ≥ 2 points and Total Symptom Score (TSS) > 50% and (2) NIS-LL ≥ 2 points only. Nineteen baseline covariates were evaluated using separate logistic regression models and either both NIS-LL and TSS or NIS-LL response definitions. Results Intention-to-treat analysis included 567 patients. Actovegin treatment compared to placebo was associated with better odds of response (OR [95% CI] of 1.73 [1.21–2.48] for definition 1 and 1.94 [1.33–2.84] for definition 2). Significant interaction with actovegin treatment was noted only for baseline use of angiotensin receptor blockers (ARBs)/angiotensinogen converting enzyme inhibitors (ACEIs), resulting in a reduced treatment response (P = 0.03). Conclusions Actovegin treatment was associated with a clinically meaningful response in neuropathic symptoms and/or impairments in patients with symptomatic DSPN. Since only one predictor of response to actovegin treatment was identified, this drug seems an appropriate therapy for the majority of patients with DSPN.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called “incretin-based therapies” (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on various outcomes and inconsistencies observed in the trials is provided. Overall, available data is favourable to the early deployment of GLP-1RAs in clinical practice, fully in line with recommendations from international scientific guidelines, and based on their effects on glucose metabolism parameters, body weight reduction and CV outcomes. Evidence further suggest that the CV benefits of GLP-1RAs may not be a class effect, with GLP-1 analogues having a greater benefit rather than exendin-based agents.

Aims To examine the prevalence of diabetic chronic kidney disease (DCKD) and its risk factors in adult Greek subjects with type 2 diabetes mellitus (T2DM) in a population from hospital-based diabetes clinics. Methods This is a cross-sectional multicentre study based on data collected from Greek hospital-based diabetes clinics from June 2015 to March 2016. DCKD severity was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines. Multivariate analyses assessed the associations between DCKD and its potential risk factors. Results Among the entire population (n = 1759), the overall prevalence of DCKD was 45% including mild, moderate and severe CKD. Older age, male gender, body-mass index, lack of exercise and diabetes duration were significantly associated with DCKD. Conclusions In Greece, DCKD in T2DM is highly prevalent. It is significantly associated with demographic and lifestyle parameters, as well as T2DM complications, suggesting that further efforts to prevent DCKD should be addressed to subjects with specific characteristics.

Platelet dysfunction plays a role in diabetic macrovascular complications. Several studies have assessed the effect of oral hypoglycemic agents (OHAs) on platelet function. Data from both in vivo and in vitro studies show a favorable effect for most of the traditional glucose-lowering therapies, while evidence is limited for the newer ones. Metformin, sulfonylureas, glitazones and acarbose exert a favorable effect on platelet function. Among incretin therapies, only sitagliptin has so far been demonstrated to have a beneficial effect on platelet aggregation. More in vivo and in vitro evidence is required to increase our knowledge on any potential beneficial effects of OHAs on platelet function. Any such effect may have implications for the reduction of cardiovascular risk in type 2 diabetes mellitus.

Aims To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). Methods We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing’s cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. Results CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). Conclusions CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.

Vitamin D has received increasing interest for its beneficial effect on health. Beyond its conventional role in bone metabolism, emerging evidence suggests a possible link between low vitamin D levels and cardiovascular disease (CVD), including peripheral arterial disease (PAD), and cardiovascular risk factors. Vitamin D interacts either directly with the vascular tree or indirectly through its association with cardiovascular risk factors, but the exact mechanism remains controversial. This review outlines the association between hypovitaminosis D and PAD. Both entities are quite prevalent in the general population and, therefore, their potential association might have important clinical implications. Whether vitamin D deficiency represents a novel risk factor for PAD/CVD, and whether vitamin D supplementation would reduce the burden of CVD still remains to be answered. Until then, vitamin D intake is not recommended for PAD/CVD prevention. Outdoor physical activity, coupled with adequate but safe sun exposure, is a healthy lifestyle practice suggested for the prevention of both PAD and hypovitaminosis D.

Objective Low Ankle-Brachial Blood Pressure Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease (PAD). We sought to investigate the association of low ABI with early risk of stroke recurrence in patients with acute cerebral ischemia (ACI) and without history of symptomatic PAD. Methods Consecutive patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and no previous history of PAD were prospectively evaluated with ABI measurements. Demographic characteristics, vascular risk factors and secondary prevention therapies were documented. An ABI ≤0.90 in either leg was considered as evidence of asymptomatic PAD, and an ABI >0.90 was considered as normal. Patients with elevated ABI (>1.30) were excluded. The outcome of interest was recurrent stroke during 30-day follow-up. Results A total of 176 patients with acute cerebral ischemia (mean age 64 ± 14 years, 59.1% men, 76.7% AIS) were evaluated. Asymptomatic PAD was detected in 14.8% (95%CI: 10.2–20.8%) of the studied population. The following factors were independently associated with low ABI on multivariate logistic regression models, after adjustment for potential confounders: coronary artery disease ( p = 0.008), diabetes mellitus ( p = 0.017) and increasing age ( p = 0.042). The cumulative 30-day recurrence rate was higher in patients with low ABI (19.2%; 95%CI: 4.1–34.3) compared to the rest (3.3%; 95%CI: 0.4–6.2%; p = 0.001). Atherothrombotic stroke (ASCO grade I; p p = 0.002) and low ABI ( p = 0.004) were independent predictors of stroke recurrence on multivariate Cox regression models adjusting for confounders. Conclusions Low ABI appears to be associated with a higher risk of early recurrent stroke in patients with ACI and no history of symptomatic PAD.

The present review outlines the various issues of breast pathology in diabetes. Diabetic mastopathy is an uncommon proliferation of fibrous tissue in the breast that mimics tumour. Breast arterial calcifications represent calcium deposits in the media of arterioles and are more frequently detected on mammograms of diabetic subjects. Importantly, type 2 diabetes mellitus (T2DM) has been associated with breast cancer, but the mechanism underlying this association is complex, since the two entities frequently co-exist and seem to share common aetiological factors and pathways. Furthermore, diabetes has been suggested to negatively affect breast cancer outcomes, but it is unclear whether better glycaemic control would ameliorate prognosis. Preliminary data suggest that antidiabetic treatment may also influence both the incidence and prognosis of breast cancer. However, available evidence is inconclusive and further research is needed. Therefore, treatment of diabetes should not be determined by its potential effect on breast cancer.

Neuropathy needs to be diagnosed early to prevent complications, such as neuropathic pain or the diabetic foot. It is obvious that diagnosis of neuropathy needs to be improved. New peripheral nerve function tests that appear to facilitate diagnosis are now emerging. This review outlines the new tests that have been proposed for the diagnosis of diabetic distal symmetric polyneuropathy, the commonest form of neuropathy in diabetes. New tests are classified into those mainly assessing large-fiber function (tactile circumferential discriminator, steel ball-bearing, and automated nerve conduction study) and those mainly assessing small-fiber function (NeuroQuick and Neuropad). Emerging tests are promising but must be evaluated in prospective studies. Moreover, their cost-effectiveness needs more careful appraisal. The clinician should, therefore, still rely on established modalities to diagnose neuropathy, but wider use of the new tests is expected in the near future.

The manifestations of diabetes in the hand were much discussed in the 1970s and 1980s. The present review aims to revisit the diabetic hand and to discuss the pathology of the hand that may be clinically important in diabetic patients. In the strict sense of the term, the "diabetic hand" encompasses the three most widely studied conditions which have traditionally been associated with diabetes, namely limited joint mobility, Dupuytren's contracture and trigger finger. There is evidence that these entities are significantly more frequent in patients with diabetes and also that they may be associated with diabetes duration, poor metabolic control and presence of microvascular complications. In a more general sense, though, there are other conditions affecting the hands, which also occur more frequently in diabetes. From a practical point of view, increased alertness both for neuropathic hand ulcers in patients with profound neuropathy and for diabetic hand infections is absolutely necessary. Recently, reduced hand strength is beginning to be recognized as a further complication of diabetes. Thus, the hand may reveal substantial pathology in diabetes, and ideally, clinical examination should not ignore it.

Objective: To investigate the potential association between serum inflammatory cytokine levels and post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure. Patients and methods: The study included 42 patients (group A: 20 men, mean age of 54.5 ± 6.8 years) with NYHA I or II heart failure and 54 patients (group B: 25 men, mean age of 52.9 ± 7.1 years) without heart failure. All patients had undergone total thyroidectomy and were euthyroid on a stable thyroxine replacement dose. Serum Interleukin-1b (IL-1b), Tumor Necrosis Factor α (TNF-α), Interleukin-6 (IL-6), TSH, T 3, T 4 , fT 3 and fT 4 were measured. Results: Both groups exhibited a significant positive correlation between IL-6 and levothyroxine replacement dosage (group A: r = 0.708, p r = 0.345, p = 0.012) and a negative correlation between IL-6 and T 3 (group A: r = −0.342, p = 0.023, group B: r = −0.294, p = 0.035). Significant independent predictors of levothyroxine replacement dosage were IL-6 ( p p = 0.007) in group A (58.3% of dosage variation) and only IL-6 ( p = 0.012) in group B (10.1% of dosage variation). Conclusions: In both groups, a significant positive correlation was observed between IL-6 and levothyroxine replacement dosage, but this correlation was stronger in group A. In the same group, there was evidence for a more pronounced influence of cytokines on levothyroxine dosage.

The present study was undertaken to assess the effect of statins on collagen type I degradation and C-reactive protein in patients with coronary artery disease and atrial fibrillation. One hundred six patients with coronary artery disease and atrial fibrillation were studied: 40 (36 men, mean age 72 +/- 8 years) treated with a statin and 66 (48 men, mean age 74 +/- 9 years) not treated with a statin. Serum concentrations of carboxy-terminal telopeptide of collagen type I, an index of collagen type I degradation, and high-sensitivity C-reactive protein were measured in all patients. Carboxy-terminal telopeptide of collagen type I levels were significantly higher (p0.001) in statin-treated patients (0.64 ng/ml, 95% confidence interval [CI] 0.57 to 0.71) compared with nonstatin-treated patients (0.38 ng/ml, 95% CI 0.31 to 0.44). These changes were independent of cholesterol levels (before or after therapy). Statin-treated patients had significantly lower (p0.001) C-reactive protein levels (0.25 mg/dl, 95% CI 0.23 to 0.28) compared to statin nonusers (1.1 mg/dl, 95% CI 0.92 to 1.25). In conclusion, this study suggests that therapy with statins in patients with coronary artery disease and atrial fibrillation is associated with an increase in collagen degradation and an attenuation of inflammation, independently of cholesterol lowering.

Objective: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. Patients and methods: The study included 40 patients (12 men) with a mean age of 56.52 ± 6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, as well as TSH, T 3 and T 4 were measured (ELISA). Results: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose ( r = 0.551, p = 0.001) and with dose per kilogram of body weight ( r = 0.482, p = 0.002). There was also a significant negative linear correlation between serum IL6 and T 3 ( r = −0.322, p = 0.043), as well as between serum IL6 and T 3 /T 4 ratio ( r = −0.332, p = 0.036). A further significant ( r = 0.419, p = 0.007) positive association was demonstrated between IL6 and TNF-α. However, no association was found between T 3 or T 3 /T 4 ratio and TNF-α or IL1b. Conclusions: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T 3 and T 3 /T 4 ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T 3 and imply a role for IL6 in determining thyroxine replacement dose among these patients.

The presence of systemic inflammation determined by elevations in high-sensitivity C-reactive protein (hs-CRP) has been associated with persistence of atrial fibrillation (AF). The influence of inflammation markers, such as hs-CRP, on the recurrences of lone AF, however, has not been clarified. We tested the hypothesis of whether, in patients with a first paroxysmal episode of lone AF, the hs-CRP levels were elevated, and whether elevated hs-CRP could predict the recurrence rate of lone AF in patients without antiarrhythmic drugs. Using a case-control study design, the hs-CRP levels in 125 patients with a documented symptomatic first paroxysmal episode of lone AF was compared with the hs-CRP levels in 65 control patients. hs-CRP levels are presented as median values with the interquartile range (25th to 75th percentiles). The hazard ratio compared the 75th percentile of hs-CRP with the 25th percentile. In the arrhythmia group, hs-CRP was higher than in the control patients (median 0.23 mg/dl, interquartile range 0.12 to 0.49, vs 0.087 mg/dl, interquartile range 0.058 to 0.098, p

It has been reported that circulating matrix metalloproteinase (MMP) levels are upregulated in patients with chronic heart failure. However, experimental studies indicate that differences in the profiles of MMPs and tissue inhibitors of metalloproteinase (TIMPs) may exist in ischemic compared with nonischemic cardiomyopathy. This study examined whether circulating levels of MMPs and TIMP-1 are related to the pathogenesis of heart failure. Circulating levels of MMP-2, MMP-3, and TIMP-1 were assessed in 52 patients with compensated end-stage chronic heart failure, including 26 patients (mean 64 +/- 7 years; 10 men) with ischemic cardiomyopathy (IC) and 26 (mean age 66 +/- 6 years; 14 men) with idiopathic dilated cardiomyopathy (IDC). Serum MMP-2 (p0.001) and MMP-3 (p0.001) levels were higher in patients with IDC than in those with IC. Serum TIMP-1 levels were lower in patients with IDC (p = 0.011) than in those with IC. This study shows that in patients with compensated end-stage chronic heart failure, circulating levels of MMP-2, MMP-3, and TIMP-1 are associated with the pathogenesis of heart failure.

Little is known regarding the outcomes of endovascular and surgical treatment of penetrating ulcers in the abdominal aorta. The potential benefit of conservative management of asymptomatic disease is also debatable. A systematic review of the literature was undertaken to investigate these issues.