Expression of Circulating miR-21 and -29 and their Association with Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is characterized by myocardial hypertrophy, fibrosis, and sarcomeric disarray. OBJECTIVE: To evaluate the expression levels of circulating miR-21 and -29 in patients with HCM and their association with clinical characteristics and myocardial fibrosis. METHODS: In this case-control study, 27 subjects with HCM, 13 subjects with hypertensive cardiomyopathy, and 10 control subjects were enrolled. Evaluation of patients' functional capacity was made by the six-minute walk test. Echocardiographic measurements of left ventricle systolic and diastolic function were conducted. Cardiac magnetic resonance late gadolinium enhancement (LGE) -through a semiquantitative evaluation- was used in the assessment of myocardial fibrosis extent in HCM patients. The expression of miR-21 and -29 in peripheral blood samples of all patients was measured via the method of quantitative reverse transcription polymerase chain reaction. RESULTS: Circulating levels of miR-21 were higher in both hypertensive and HCM (p<0.001) compared to controls, while expression of miR-29 did not differ between the three studied groups. In patients with HCM and LGE-detected myocardial fibrosis in more than 4 out of 17 myocardial segments, delta CT miR-21 values were lower than in patients with myocardial LGE in 3 or fewer myocardial segments (2.71 ± 1.06 deltaCT vs. 3.50 ± 0.55 deltaCT, p=0.04), indicating the higher expression of circulating miR-21 in patients with more extensive myocardial fibrosis. CONCLUSION: MiR-21 was overexpressed in patients with HCM and hypertensive cardiomyopathy. Importantly, in patients with HCM, more extensive myocardial fibrosis was associated with higher levels of miR-21.

Diabetes Mellitus in Acute Coronary Syndrome.

The global prevalence of diabetes mellitus (DM) has led to a pandemic, with significant microvascular and macrovascular complications including coronary artery disease (CAD), which worsen clinical outcomes and cardiovascular prognosis. Patients with both acute coronary syndrome (ACS) and DM have worse prognosis and several pathophysiologic mechanisms have been implicated including, insulin resistance, hyperglycemia, endothelial dysfunction, platelet activation and aggregations as well as plaque characteristics and extent of coronary lesions. Therefore, regarding reperfusion strategies in the more complex anatomies coronary artery bypass surgery may be the preferred therapeutic strategy over percutaneous coronary intervention while both hyperglycemia and hypoglycemia should be avoided with closed monitoring of glycemic status during the acute phase of myocardial infraction. However, the best treatment strategy remains undefined. Non-insulin therapies, due to the low risk of hypoglycemia concurrently with the multifactorial CV protective effects, may be proved to be the best treatment option in the future. Nevertheless, evidence for the beneficial effects of glucagon like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors and sodium glycose cotransporter 2 inhibitors, despite accumulating, is not robust and future randomized control trials may provide more definitive data.

Novel Biomarkers and Their Role in the Diagnosis and Prognosis of Acute Coronary Syndrome.

The burden of cardiovascular diseases and the critical role of acute coronary syndrome (ACS) in their progression underscore the need for effective diagnostic and prognostic tools. Biomarkers have emerged as crucial instruments for ACS diagnosis, risk stratification, and prognosis assessment. Among these, high-sensitivity troponin (hs-cTn) has revolutionized ACS diagnosis due to its superior sensitivity and negative predictive value. However, challenges regarding specificity, standardization, and interpretation persist. Beyond troponins, various biomarkers reflecting myocardial injury, neurohormonal activation, inflammation, thrombosis, and other pathways are being explored to refine ACS management. This review article comprehensively explores the landscape of clinically used biomarkers intricately involved in the pathophysiology, diagnosis, and prognosis of ACS (i.e., troponins, creatine kinase MB (CK-MB), B-type natriuretic peptides (BNP), copeptin, C-reactive protein (CRP), interleukin-6 (IL-6), d-dimers, fibrinogen), especially focusing on the prognostic role of natriuretic peptides and of inflammatory indices. Research data on novel biomarkers (i.e., endocan, galectin, soluble suppression of tumorigenicity (sST2), microRNAs (miRNAs), soluble oxidized low-density lipoprotein receptor-1 (sLOX-1), F2 isoprostanes, and growth differentiation factor 15 (GDF-15)) are further analyzed, aiming to shed light on the multiplicity of pathophysiologic mechanisms implicated in the evolution of ACS. By elucidating the complex interplay of these biomarkers in ACS pathophysiology, diagnosis, and outcomes, this review aims to enhance our understanding of the evolving trajectory and advancements in ACS management. However, further research is necessary to establish the clinical utility and integration of these biomarkers into routine practice to improve patient outcomes.

The incidence of recurrent cardiovascular events among acute coronary syndrome patients treated with generic or original clopidogrel in relation to their sociodemographic and clinical characteristics. The Aegean study.

INTRODUCTION: The use of generic drugs is continuously growing; however, there are limited epidemiological data regarding the therapeutic equivalence of each original drug formulation with its generic counterparts. We evaluated the 12-month composite endpoint of recurrent acute myocardial infarction, ischaemic stroke, cardiac deaths, or hospitalisation due to a major bleeding in acute coronary syndrome (ACS) patients treated with original clopidogrel or a generic clopidogrel formulation, in relation to sociodemographic and clinical characteristics. MATERIAL AND METHODS: Consecutive Greek ACS patients (n = 1194) hospitalised in the Aegean islands and the Attica region were enrolled. Clopidogrel treatment was recorded either as original clopidogrel hydrogen sulphate (Plavix®/Iscover®) or as a generic clopidogrel besylate formulation (Clovelen®). The composite endpoint was recorded at 12-month follow-up. RESULTS: The 12-month composite endpoint was 3.9% (4.6% in the Aegean islands and 3.5% in the Attica area, p > 0.05). The respective incidence in men was 4.0% and in women 3.8% (p > 0.05). Overall, generic and original clopidogrel use was 87% and 13% of patients, respectively. No significant differences were observed between original and generic clopidogrel use and 12-month composite endpoint incidence. Subgroup analysis with gender, region of residence, and clinical and lifestyle factors as strata did not reveal any significant outcomes. Haemorrhage incidence did not exceed 1% in the total sample. CONCLUSIONS: The use of a generic clopidogrel besylate formulation was quite high in both urban and insular areas of Greece and had similar efficacy and safety profile with the original clopidogrel salt, supporting the routine use of this low-cost generic clopidogrel in the management of cardiovascular disease patients.

The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment.

BACKGROUND AND AIMS: Smoking is associated with increased inflammatory process and impairment of fibrinolytic status. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. We aimed to evaluate the impact of CGJ on smoking-induced impairment of inflammatory and fibrinolytic status in healthy smokers. METHODS: We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on three occasions (day 0: baseline, day 7 and day 14) in a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and 20 min after (Sm20) cigarette smoking. Serum levels of intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured as markers of inflammatory and fibrinolytic status, respectively. RESULTS: Treatment with CGJ reduced pSm sICAM-1 levels (p < 0.001), while placebo had no impact on ICAM-1 levels (p = 0.31). Moreover, treatment with CGJ decreased pSm values of PAI-1 (p < 0.001) while placebo had no impact on PAI-1 levels (p = 0.89). Smoking induced an elevation in PAI-1 levels after smoking compared to pro-smoking levels in all study days and in both arms (CGJ and placebo) of the study (p < 0.001 for all). Interestingly, CGJ compared to placebo, attenuated the acute smoking increase in sICAM-1 and PAI-1 levels (p < 0.001 and p = 0.005 respectively). CONCLUSIONS: CGJ consumption improved inflammatory and fibrinolytic status in healthy smokers and attenuated acute smoking induced increase in ICAM-1 and PAI-1 levels. These findings shed further light on the favorable effects of flavonoids in cardiovascular health.

Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients.

OBJECTIVE: Endothelial function is an independent predictor of prognosis in heart failure (HF) subjects. Statins, beyond their lipid lowering role, exert beneficial effect in patients with atherosclerosis. In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function, bone marrow-derived endothelial progenitor cells (EPC) mobilization and inflammatory status according to HF patient status. METHODS: We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). The number of circulating CD34(+)/CD133(+)/KDR(+) EPCs was evaluated by flow cytometry. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery. Serum levels of tumor necrosis factor alpha (TNF-α) were measured by ELISA. RESULTS: Treatment with atorvastatin 40 mg/d significantly increased circulating EPC (p = 0.002), FMD (p = 0.001) and reduced TNF-α (p = 0.01) compared to baseline. Similarly, treatment with atorvastatin 10 mg/day increased circulating EPC (p = 0.01), FMD (p = 0.08) and reduced TNF-α (p = 0.01) compared to baseline. Interestingly, with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III (p = 0.03). CONCLUSIONS: Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects. Moreover, these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects.

Favorable effects of concord grape juice on endothelial function and arterial stiffness in healthy smokers.

BACKGROUND: Smoking is associated with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examined the impact of CGJ on arterial wall properties in healthy smokers. METHODS: We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 minutes after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS: Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P < 0.001) and the placebo group (P < 0.001). Compared with placebo, CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CONCLUSIONS: CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.

Diagnostic and therapeutic potentials of microRNAs in heart failure.

MicroRNAs are a class of evolutionarily small non-coding RNAs of 19 to 25 nucleotides in length, that represent one of the most exciting areas of current medical science as they can regulate a complex regulatory network of gene expression and physiologic processes including differentiation, proliferation and apoptosis in a highly context dependent fashion. Recently, their role in cardiovascular disease and in the regulation of cardiomyocyte size and function, in the action potential, in angiogenesis and in mitochondrial function was recognized. Importantly, they have been evaluated for their prognostic and diagnostic role in heart failure and modification of specific microRNAs levels has been tested as a therapeutic option in experimental heart failure models. In this review article we refer the most emerging evidence, concerning the role of microRNAs in myocardial development in heart failure pathophysiology and prognosis, and their therapeutic implications.

The impact of physical activity on endothelial function in middle-aged and elderly subjects: the Ikaria study.

INTRODUCTION: Exercise training and physical activity (PA) have substantial vascular and cardiac health benefits. Ikaria Island has been recognised as having one of the highest longevity rates worldwide and a high percentage of healthy ageing. We examined the relationship between endothelial function and levels of habitual PA to evaluate the factors related to healthy ageing in this population. METHODS: The study was conducted on a subgroup population of the IKARIA study consisting of 185 middle-aged (40-65 years) and 142 elderly subjects (66-91 years). Endothelial function was evaluated by ultrasound measurement of flow-mediated dilatation (FMD). PA was evaluated using the shortened version of the self-reported International Physical Activity Questionnaire (IPAQ). Subjects in the low PA group (<500 MET/ min/week) were considered as physically inactive and the rest as active. RESULTS: In the overall study population FMD was inversely associated with age (r=-0.24, p<0.001) and middle-aged subjects had higher FMD compared with the elderly (6.26 ± 3.31% vs. 5.21 ± 2.95%, p=0.003). Multiple linear regression analysis revealed that among middle-aged subjects the physically active had higher FMD compared with the physically inactive. Physically active subjects in the middle-aged group showed higher FMD compared with the physically active elderly (p=0.008). However, there was no difference in FMD values between middle-aged inactive subjects and the elderly physically active (p=NS). CONCLUSION: The present study revealed that increased PA was associated with improved endothelial function in middle-aged subjects and that PA in elderly subjects can ameliorate the devastating effects of ageing on arterial wall properties.

Consumption of a boiled Greek type of coffee is associated with improved endothelial function: the Ikaria study.

OBJECTIVE: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria. METHODS: The analysis was conducted on 142 elderly subjects (aged 66-91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as 'low' (< 200 ml/day), 'moderate' (200-450 ml/day), or 'high' (> 450 ml/day). RESULTS: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a 'low', 48% a 'moderate' and 13% a 'high' daily coffee consumption. There was a linear increase in FMD according to coffee consumption ('low': 4.33 ± 2.51% vs 'moderate': 5.39 ± 3.09% vs 'high': 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035). CONCLUSIONS: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.

Association of sarcoidosis with endothelial function, arterial wall properties, and biomarkers of inflammation.

BACKGROUND: Sarcoidosis is an inflammatory disease, which may affect vascular function. The study was designed to assess the impact of sarcoidosis on endothelial function and arterial stiffness. METHODS: Eighty-seven sarcoidosis patients and eighty-seven matched healthy subjects (Cl) were included in the study. Sarcoidosis patients were divided into two groups. Group 1 included patients never treated and group 2 included patients receiving cortisone treatment. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AI75) as a measure of arterial wave reflections. Serum levels of soluble intercellular adhesion molecule-1 and tumor necrosis factor-α (TNF-α), were measured. RESULTS: In the totality of the population, sarcoidosis patients had significantly lower FMD (P < 0.01) and significantly higher AI75 (P < 0.05). There was also a significant difference, between group 1, and Cl in FMD and AI75, but there was no difference between group 2 and Cl in FMD and AI75. AI75 values were significantly correlated with serum levels of intercellular adhesion molecule-1 (ICAM-1) (r = 0.370, P < 0.01) and TNF-α (r = 0.219, P = 0.049). CONCLUSIONS: In the present study, we have shown that sarcoidosis patients have impaired endothelial function and increased arterial stiffness. Sarcoidosis patients on cortisone treatment had no differences compared to controls on the vascular parameters. Moreover, there was a significant correlation between inflammatory process and vascular function impairment. These findings indicate that sarcoidosis patients have impaired vascular function and increased inflammatory status, which may improve with cortisone treatment.

Sociodemographic and lifestyle statistics of oldest old people (>80 years) living in ikaria island: the ikaria study.

Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the "Blue Zones". Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the "Blue Zones". The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the "secrets" of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life.