Myocardial infarction due to left main coronary artery total occlusion: A unique electrocardiographic presentation.

Left main coronary artery (LMCA) total occlusion typically presents as anterolateral ST-segment myocardial infarction with or without right bundle branch block with left anterior fascicular block, and ST-segment elevation in aVR. On the contrary to the previously described electrocardiographic pattern we describe a distinct electrocardiographic presentation in a patient with total LMCA occlusion characterized by the presence of complete LBBB co-existing with upsloping ST-segment depression in precordial leads leading to symmetrical, tall, positive T waves, the so called de Winter's sign.

Novel Pharmacological Therapies for the Management of Hyperlipoproteinemia(a).

Lipoprotein(a) [Lp(a)] is a well-established risk factor for cardiovascular disease, predisposing to major cardiovascular events, including coronary heart disease, stroke, aortic valve calcification and abdominal aortic aneurysm. Lp(a) is differentiated from other lipoprotein molecules through apolipoprotein(a), which possesses atherogenic and antithrombolytic properties attributed to its structure. Lp(a) levels are mostly genetically predetermined and influenced by the size of LPA gene variants, with smaller isoforms resulting in a greater synthesis rate of apo(a) and, ultimately, elevated Lp(a) levels. As a result, serum Lp(a) levels may highly vary from extremely low to extremely high. Hyperlipoproteinemia(a) is defined as Lp(a) levels > 30 mg/dL in the US and >50 mg/dL in Europe. Because of its association with CVD, Lp(a) levels should be measured at least once a lifetime in adults. The ultimate goal is to identify individuals with increased risk of CVD and intervene accordingly. Traditional pharmacological interventions like niacin, statins, ezetimibe, aspirin, PCSK-9 inhibitors, mipomersen, estrogens and CETP inhibitors have not yet yielded satisfactory results. The mean Lp(a) reduction, if any, is barely 50% for all agents, with statins increasing Lp(a) levels, whereas a reduction of 80-90% appears to be required to achieve a significant decrease in major cardiovascular events. Novel RNA-interfering agents that specifically target hepatocytes are aimed in this direction. Pelacarsen is an antisense oligonucleotide, while olpasiran, LY3819469 and SLN360 are small interfering RNAs, all conjugated with a N-acetylgalactosamine molecule. Their ultimate objective is to genetically silence LPA, reduce apo(a) production and lower serum Lp(a) levels. Evidence thus so far demonstrates that monthly subcutaneous administration of a single dose yields optimal results with persisting substantial reductions in Lp(a) levels, potentially enhancing CVD risk reduction. The Lp(a) reduction achieved with novel RNA agents may exceed 95%. The results of ongoing and future clinical trials are eagerly anticipated, and it is hoped that guidelines for the tailored management of Lp(a) levels with these novel agents may not be far off.

Differential prognostic value of resistin for cardiac death in patients with coronary artery disease according to the presence of metabolic syndrome.

Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in stable coronary artery disease (CAD) patients. We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death and secondary hospitalizations for acute coronary syndrome, arrhythmic event or ischemic stroke. Follow-up data were obtained from 703 patients of whom 79 had a cardiac death (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r = 0.159, p < 0.001) and IL-6 (r = 0.165, p = 0.002), and negatively with high-density lipoprotein-cholesterol (r = - 0.176, p < 0.001). Resistin levels could not predict cardiac death [HR 1.044; 95% CI 0.994-1.096; p = 0.087] neither secondary endpoints [HR 1.025; 95% CI 0.983-1.068; p = 0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independently associated with cardiac death after adjustment for conventional risk factors [HR 1.121; 95% CI 1.045-1.204; p = 0.002). Further adjustment for ejection fraction of left ventricle (LVEF) did not change the association (HR 1.145; 95% CI 1.057-1.240; p = 0.001). Patients with resistin values ≥ 7.6 ng/mL (median level) had 2.8 times higher risk of cardiac death compared to those with resistin levels < 7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR 2.882; 95% CI 1.311-6.336; p = 0.008). Resistin is independently associated with cardiac death in patients with stable CAD and MS.

Statins and statin intensity in peripheral artery disease.

Background: Peripheral artery disease (PAD) affects more than 202 million people worldwide. Several studies have shown that patients with PAD are often undertreated, and that statin utilization is suboptimal. European and American guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on lower extremities PAD endpoints and examine whether statin dose (high vs. low intensity) impacts outcomes. Patients and methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of use of statins vs. no statins for PAD patients or studies comparing high vs. low intensity statins were considered to be potentially eligible. We excluded studies with only critical limb threatening ischemia (CLTI) patients. The Medline (PubMed) database was searched up to January 31, 2021. A random effects meta-analysis was performed. Results: In total, 39 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) patients were on statins vs. 139,645 (50.66%) who were not on statins. Statin use was associated with a reduction in all cause-mortality by 42% (HR: 0.58, 95% CI: 0.49-0.67, p<0.01) and cardiovascular death by 43% (HR: 0.57, 95% CI: 0.40-0.74, p<0.01). Statin use was associated with an increase in amputation-free survival by 56% (HR: 0.44, 95% CI: 0.30-0.58, p<0.01). The risk of amputation and loss of patency were reduced by 35% (HR: 0.65, 95% CI: 0.41-0.89, p<0.01) and 46% (HR: 0.54, 95% CI: 0.34-0.74, p<0.01), respectively. Statin use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR: 0.65, 95% CI: 0.51-0.80, p<0.01) and myocardial infarction rates by 41% (HR: 0.59, 95% CI: 0.33-0.86, p<0.01). Among patients treated with statins, the high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR: 0.64, 95% CI: 0.54-0.74, p<0.01) compared to patients treated with low intensity statins. Conclusions: Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MACE, risk for amputation, or loss of patency. Higher statin dose seems to be associated with improved outcomes.

The association of animal and plant protein with successful ageing: a combined analysis of MEDIS and ATTICA epidemiological studies.

OBJECTIVE: The aim of the present study was to investigate the differences between the consumption of plant-based v. animal-based protein-rich diets on successful ageing, as well as to identify the optimal combination of dietary protein intake for facilitating successful ageing in people aged >50 years. DESIGN: A combined analysis was conducted in older adults of the ATTICA and MEDIS population-based cross-sectional studies. Anthropometrical, clinical and sociodemographic characteristics, lifestyle parameters, dietary habits and level of protein intake were derived through standard procedures. Successful ageing was evaluated using the validated Successful Aging Index (SAI) composed of ten health-related social, lifestyle and clinical characteristics. SETTING: Athens area and twenty Greek islands. PARTICIPANTS: A total of 3349 Greek women and men over 50 years old. RESULTS: Participants with high consumption of plant proteins were more likely to be male, physically active, with higher daily energy intake, higher adherence to the Mediterranean diet and higher level of SAI (P < 0·001). Participants with 'Low animal & High plant' and 'High animal & High plant' protein consumption had a 6 and 7 % higher SAI score, respectively, compared with the other participants (P < 0·001). In contrast, 'Low animal & Low plant' and 'High animal & Low plant' protein intake was negatively associated with SAI as compared to the combination of all other consumption categories (P < 0·02). CONCLUSIONS: The consumption of a plant-based protein-rich diet seems to be a beneficial nutritional choice that should be promoted and encouraged to older people since it may benefit both individual's health and prolong successful ageing.

Nutrition, dietary habits, and weight management to prevent and treat patients with peripheral artery disease.

Peripheral artery disease (PAD) affects 3%-10% of the Western population and if remains untreated can have devastating consequences to patients and their families. This review article analyzes how healthy dietary habits can decrease PAD rates when applied in the general population. The aim is to focus on dietary, nutritional and weight management interventions in patients with established PAD. Most adults with PAD are overweight or obese, while three out of four patients are characterized by deficiencies in vitamins and minerals. Weight loss interventions when needed and specialized dietary plans should be routinely recommended in patients with PAD. Appropriate nutritional support is of paramount importance in patients with advanced stages of PAD (critical limb ischemia).

Identification and characterization of a rare variant in apolipoprotein A-IV, p.(V336M), and evaluation of HDL functionality in a Greek cohort with extreme HDL cholesterol levels.

High-Density Lipoprotein cholesterol (HDL-C) levels do not correlate well with Coronary Artery Disease (CAD) risk, while HDL functionality affects atherogenesis and is a better prognostic marker for CAD. Often, the extreme HDL-C levels have a multigenic origin. Here, we searched for single-nucleotide polymorphisms (SNPs) in ten genes of HDL metabolism in a Greek cohort with very low (<10th percentile, n = 13) or very high (>90th percentile, n = 21) HDL-C. We also evaluated the association between HDL-C levels, HDL functionality (anti-oxidant capacity) and CAD in the subjects of this cohort. Individuals with low HDL-C levels had higher triglyceride levels, lower apoA-I levels, decreased HDL anti-oxidant capacity and higher incidence of CAD compared with individuals with control or high HDL-C levels. With next generation sequencing we identified 18 exonic SNPs in 6 genes of HDL metabolism and for selected amino acid changes we performed computer-aided structural analysis and modeling. A previously uncharacterized rare apolipoprotein A-IV variant, apoA-IV [V336M], present in a subject with low HDL-C (14 mg/dL) and CAD, was expressed in recombinant form and structurally and functionally characterized. ApoA-IV [V336M] had similar α-helical content to WT apoA-IV but displayed a small thermodynamic stabilization by chemical unfolding analysis. ApoA-IV [V336M] was able to associate with phospholipids but presented reduced kinetics compared to WT apoA-IV. Overall, we identified a rare apoA-IV variant in a subject with low HDL levels and CAD with altered biophysical and phospholipid binding properties and showed that subjects with very low HDL-C presented with HDL dysfunction and higher incidence of CAD in a Greek cohort.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

The association of protein and carbohydrate intake with successful aging: a combined analysis of two epidemiological studies.

PURPOSE: Previous studies have reported associations between levels of protein and carbohydrate intake with several health outcomes. Yet, their effect on successful (or healthy) aging remains unknown. The purpose of the present work was to investigate the association of protein and carbohydrate intake levels with successful aging. METHODS: A cross-sectional analysis was carried out on the participants of two epidemiological studies; the ATTICA and the MEDIS studies. Anthropometrical, clinical and socio-demographic characteristics, dietary habits, and lifestyle parameters were derived through standard procedures. Successful aging was evaluated using a validated index (SAI) composed of 10 health-related social, lifestyle and clinical characteristics. RESULTS: SAI levels were lower in low protein-high carbohydrate diet group (B = - 0.08, p = 0.04), but higher in high protein-high carbohydrate group (B = 0.06, p = 0.04), as compared to low protein and low carbohydrate diet, in participants living in insular areas. Protein-carbohydrate diet was not associated with SAI (all p's > 0.05) among participants living in urban areas (p for diet-study interaction < 0.001). CONCLUSIONS: A high protein diet seems to be beneficial for older islanders in terms of successful aging; stating a hypothesis for a potential diet-environmental interaction that may be related to the quality of foods consumed and, consequently the sources of nutrients.

The association between homocysteine levels, Mediterranean diet and cardiovascular disease: a case-control study.

The aim was to investigate the association between homocysteine (Hcy) and acute coronary syndrome (ACS) and to test the potential moderating role of Mediterranean diet. An age and gender matched case-control study was conducted among 1491 patients with a first ACS event and 3037 adults free of cardiovascular disease (CVD). Adherence to the Mediterranean diet was measured using the MedDietScore (range 0-55). An increase in Hcy levels was associated with a 1% and 3% higher likelihood of ACS among younger (<45 yrs) and middle-aged (45-60yrs) adults (p's < 0.05), but not in older adults (p = 0.13). Moreover, Hcy was associated with 3% (95%CI: 1.01-1.06) increase in the likelihood of ACS among those who did not adhere to the Mediterranean diet. Hence, Hcy is apparently independently associated with ACS among younger and middle-aged individuals. The inverse association between Mediterranean diet adherence and Hcy highlights a disease-preventing effect of the Mediterranean diet on CVD.

The Association between Green and Black Tea Consumption on Successful Aging: A Combined Analysis of the ATTICA and MEDiterranean ISlands (MEDIS) Epidemiological Studies.

Tea is one of the most-widely consumed beverages in the world with a number of different beneficial health effects, mainly ascribed to the polyphenolic content of the tea catechins. The aim of this study was to examine the consumption of green, black, or no tea, in relation to the previously validated successful ageing index (SAI; higher values "healthier" ageing) in a combined analysis of adults aged >50 years old from the ATTICA (n = 1128 adults from Athens, Greece metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek island and Mani) studies. After adjusting for age, sex, smoking, and coffee consumption, green tea was positively associated with SAI (b ± SE: 0.225 ± 0.055, p < 0.001), while black tea was negatively associated with SAI (unstandardized b coefficient ± Standard error: -0.807 ± 0.054, p < 0.001). Green tea (vs black tea) consumption, had higher odds of a SAI of over 3.58 out of 10 (OR: 1.77, 95% CI: 1.38-2.28). Green tea consumption was also associated with higher levels of physical activity (p < 0.001) and reduced likelihood of hypertension (p = 0.006) compared with black tea. Two possible mechanisms are that green tea possesses high levels of catechins such as (-)-epigallocatechin 3-gallate and l-theanine compared with black tea. Therefore, the present analysis supports both the role of green tea constituents in successful ageing, as well as its role as an important component of an overall healthy diet in adults aged 50 years and over from these two epidemiological studies.

Prothrombotic genetic risk factors in patients with very early ST-segment elevation myocardial infarction.

The contribution of prothrombotic genetic risk factors in the pathogenesis of premature acute myocardial infarction (MI) is controversial. We examined the prevalence of prothrombotic polymorphisms (G1691A of factor V gene [FV Leiden] and G20210A of prothrombin [FII] gene), deficiencies of natural anticoagulants (protein C, protein S and antithrombin III) and antiphospholipid syndrome (APS) in patients with early ST-segment elevation MI (STEMI). We recruited 255 consecutive patients who had survived a STEMI ≤ 35 years of age (224 men). The control group consisted of 400 healthy individuals matched with cases for age and sex. G20210A polymorphism of FII gene was more frequent in young patients than in controls (7.4 vs. 3.5%, p = 0.023). The odds ratio (OR) for STEMI for carriers versus non-carriers was 2.239 (95% CI 1.102-4.250). The adjusted OR for major cardiovascular risk factors was 2.569 (95% CI 1.086-6.074). The risk was increased by 22-fold (95% CI 9.192-66.517) when G20210A polymorphism was present in combination with smoking. There was no difference in the prevalence of FV Leiden between patients and controls (7.8 vs. 6.5%, p = 0.512). There was only one patient (0.4%) with protein C deficiency and one with APS (0.4%). G20210A polymorphism of FII gene may be associated with increased risk of premature STEMI and the risk increases substantially when smoking is present. The contribution of other prothrombotic disorders such as deficiencies of protein C, protein S and antithrombin III and APS was minimal in this cohort.

The fundamental importance of smoking cessation in those with premature ST-segment elevation acute myocardial infarction.

PURPOSE OF REVIEW: Smoking is the most prevalent risk factor among young patients suffering acute myocardial infarction (AMI). In this review, we will present data on the detrimental consequences of continued smoking with regard to the recurrence of coronary events after an AMI at an early age. RECENT FINDINGS: A prospective study with long-term follow-up of young survivors of AMI showed that continuation of smoking after a first episode of AMI was the strongest independent predictor of further cardiac events. In particular, persistent smokers had ∼2.5 times higher risk of a new coronary event when compared with nonsmokers. This emphasizes the fundamental importance of initiating smoking cessation treatment in all smokers with AMI during hospitalization. Extrapolating the results of previous studies showing the benefits of smoking cessation in middle-aged or elderly coronary patients, an even greater benefit should be expected in young patients because of their specific characteristics, which are presented in the current review. SUMMARY: Young persistent smokers after a premature AMI constitute a high-risk subgroup for a recurrence of cardiac events. Therefore, smoking cessation is a key issue for improving their prognosis and all smokers should be offered effective antismoking treatment at the time of initial hospitalization.

Exclusive olive oil consumption has a protective effect on coronary artery disease; overview of the THISEAS study.

OBJECTIVE: The aims of the current report are to present the demographic characteristics, clinical characteristics/biochemical indices and lifestyle habits of the population and to explore the potential association of exclusive olive oil consumption, in relation to lifestyle factors, with coronary artery disease risk. DESIGN: Demographic, lifestyle, dietary and biochemical variables were recorded. Logistic regression analysis was performed in order to estimate the relative risks of developing coronary artery disease. SETTING: The Hellenic study of Interactions between Single nucleotide polymorphisms and Eating in Atherosclerosis Susceptibility (THISEAS), a medical centre-based case-control study conducted in Greek adults. SUBJECTS: We consecutively enrolled 1221 adult patients with coronary artery disease and 1344 adult controls. RESULTS: A higher prevalence of the conventional established risk factors was observed in cases than in controls. Physical activity level was higher in controls (1·4 (sd 0·2) than in cases (1·3 (sd 0·3); P<0·001). Regarding current and ex-smokers, the case group reported almost double the pack-years of the control group (54·6 (sd 42·8) v. 28·3 (sd 26·3), respectively; P<0·001). Exclusive olive oil consumption was associated with 37 % lower likelihood of developing coronary artery disease, even after taking into account adherence to the Mediterranean diet (OR=0·63; 95 % CI 0·42, 0·93; P=0·02). CONCLUSIONS: Exclusive olive oil consumption was associated with lower risk of coronary artery disease, even after adjusting for adoption of an overall healthy dietary pattern such as the Mediterranean diet.

The impact of smoking on long-term outcome of patients with premature (≤35years) ST-segment elevation acute myocardial infarction.

BACKGROUND: There are few data regarding the long-term prognosis of young survivors of acute myocardial infarction (AMI). We explored the long-term outcome in individuals who had sustained a premature ST-segment elevation AMI. METHODS: We recruited 257 consecutive patients who had survived their first AMI ≤35years of age. Patients were followed up for up to 18years. Clinical end points included all major adverse coronary events (MACE): cardiac death, readmission for acute coronary syndrome, arrhythmias, or coronary revascularization due to clinical deterioration. RESULTS: The most prevalent risk factor at presentation was smoking (93.7%). Follow-up data were obtained from 237 patients (32.2±3.7years old). The median follow-up period was 9.1years. During follow-up, 139 (58.6%) patients reported continuation of smoking. Ninety-one (38.4%) patients had recurrent MACE (13 deaths, 59 acute coronary syndromes, 2 arrhythmias, and 17 revascularizations). Multivariable Cox regression analysis showed that persistence of smoking, left ventricular ejection fraction (LVEF), and reperfusion therapy (fibrinolysis or primary coronary angioplasty) were independent predictors of MACE after adjustment for conventional risk factors. Continuation of smoking remained an independent predictor for MACE after additional adjustments for LVEF (hazard ratio 2.154, 95% CI 1.313-3.535, P=.002) or reperfusion treatment (hazard ratio 2.327, 95% CI 1.423-3.804, P=.001). Harrell c statistic showed that the model with persistent smoking had the best discriminatory power compared with models with LVEF or reperfusion treatment. CONCLUSIONS: In the era of statins and reperfusion treatment, continuation of smoking is the strongest independent long-term predictor for recurrent MACE in young survivors of premature AMI.

Effect of green tea on postprandial antioxidant capacity, serum lipids, C-reactive protein and glucose levels in patients with coronary artery disease.

PURPOSE: Cardiovascular risk factors have been identified in the postprandial state, particularly in patients with coronary artery disease (CAD). Tea consumption has been linked to cardiovascular risk reduction, but the beneficial effect of tea has not been investigated under postprandial conditions. The objective was to examine the effect of green tea on postprandial levels of plasma total antioxidant capacity (TAC), serum lipids, C-reactive protein (CRP) and glucose in patients with CAD. METHODS: In a randomized controlled, parallel design with 2 arms, 43 patients with CAD were assigned to consume breakfast consisting of bread, butter and 330 ml water or tea (4.5 g green tea/330 ml, providing approximately 400 mg catechins). Blood samples were drawn immediately before and 1.5, 3 and 5 h after breakfast. TAC was measured in plasma with the ferric reducing antioxidant power of plasma and oxygen radical absorbance capacity assays. Total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, CRP, uric acid and pancreatic lipase levels were measured in serum. RESULTS: Tested biomarkers did not differ between tea and water group at baseline, 1.5, 3 and 5 h (P > 0.05) postprandially. However, TAC increased 1.5 and 3 h after consumption of breakfast with tea (P < 0.005), but no change was observed after consumption of breakfast with water. Serum triglycerides levels significantly increased 3 h after breakfast with water (P = 0.031), but not after breakfast with tea. Serum uric acid decreased 1.5 h after breakfast with tea (P = 0.038). Pancreatic lipase, CRP, total cholesterol, HDL-C, LDL-C and glucose levels remained unchanged after breakfast with tea at any time point (P > 0.05). CONCLUSIONS: Tea consumption did not affect selected biomarkers at any postprandial time point in patients with CAD.

Is inverse association between lipoprotein(a) and diabetes mellitus another paradox in cardiometabolic medicine?

INTRODUCTION: The impact of Type II Diabetes mellitus (T2DM) on cardiovascular disease (CVD) is well-established, while lipoprotein(a) [Lp(a)] has recently emerged as a recognized CVD risk factor. The rising prevalence of T2DM resulting from modern lifestyles and the development of specific Lp(a)-lowering agents brought the association between T2DM and Lp(a) in the forefront. AREAS COVERED: Despite advancements in T2DM treatment, diabetic patients remain at very-high risk of CVD. Lp(a) may, to some extent, contribute to the persistent CVD risk seen in diabetic patients, and the coexistence of T2DM and elevated Lp(a) levels appears to synergistically amplify overall CVD risk. The relationship between T2DM and Lp(a) is paradoxical. On one hand, high Lp(a) plasma concentrations elevate the risk of diabetic microvascular and macrovascular complications. On the other hand, low Lp(a) plasma concentrations have been linked to an increased risk of developing T2DM. EXPERT OPINION: Comprehending the association between T2DM and Lp(a) is critical due to the pivotal roles both entities play in overall CVD risk, as well as the unique aspects of their relationship. The mechanisms underlying the inverse association between T2DM and Lp(a) remain incompletely understood, necessitating further meticulous research.

Inclisiran: the preclinical discovery and development of a novel therapy for the treatment of atherosclerosis.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. Lipid lowering therapy (LLT) constitutes the cornerstone of ASCVD prevention and treatment. However, several patients fail to achieve therapeutic goals due to low treatment adherence or limitations of standard-of-care (SoC) LLTs. Inclisiran represents a pivotal low-density lipoprotein cholesterol (LDL-C) lowering agent aiming to address current unmet needs in LLT. It is the first available small interfering RNA (siRNA) LLT, specifically targeting PCSK9 mRNA and leading to post-transcriptional gene silencing (PTGS) of the PCSK9 gene. AREAS COVERED: Promising phase III trials revealed an ~ 50% reduction in LDL-C levels with subcutaneous inclisiran administration on days 1 and 90, followed by semiannual booster shots. Coupled with inclisiran's favorable safety profile, these findings led to its approval by both the EMA and FDA. Herein, the authors highlight the preclinical discovery and development of this agent and provide the reader with their expert perspectives. EXPERT OPINION: The evolution of gene-silencing treatments offers new perspectives in therapeutics. Inclisiran appears to have the potential to revolutionize ASCVD prevention and treatment, benefiting millions of patients. Ensuring widespread availability of Inclisiran, as well as managing additional healthcare costs that may arise, should be of paramount importance.

NT-proBNP/cardiac troponin T ratio >7.5 on the second day of admission can differentiate Takotsubo from acute coronary syndrome with good accuracy.

BACKGROUND: Takotsubo syndrome (TTS) is not usually diagnosed until patients with suspected acute coronary syndrome (ACS) and echocardiographically detected apical aneurysm are found to have "normal" coronary angiography (CA). Our aim was to explore whether cardiac biomarkers can contribute to the early diagnosis of TTS. METHODS: Ratios of N-terminal-pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT) both expressed in pg/mL [admission and the 3 following days] were compared in 38 patients with TTS and 114 ACS patients of whom 58 had non-ST-elevation myocardial infarction (NSTEMI). RESULTS: NT-proBNP/cTnT ratio at admission and during the following 3 days was significantly higher in TTS compared to patients with ACS [18.4 (8.7-41.7) vs 2.9 (0.8-6.8), 29.6 (14.3-53.7) vs 1.2 (0.5-2.7), 30.0 (11.6-50.9) vs 1.7 (0.5-3.0), 27.8 (11.3-42.6) vs 1.4 (0.6-2.8), respectively, all <0.001]. Βest discrimination of TTS from ACS was possible with the ratio of NT-proBNP/cTnT on the 2nd day. A cut-off value of NT-proBNP/cTnT ratio >7.5 had a sensitivity of 97.3%, a specificity of 95.4% and an accuracy of ∼96% in detecting TTS as opposed to ACS. Furthermore, the ratio of NT-proBNP/cTnT preserved its discriminatory value in the subgroup of patients with NSTEMI. In particular, an NT-proBNP/cTnT ratio >7.5 on the 2nd day had a sensitivity of 97.3%, a specificity of 91.4%, and an accuracy of 93.7% in differentiating TTS from NSTEMI. CONCLUSIONS: An NT-proBNP/cTnT ratio >7.5 on the 2nd day of admission can be useful for the early identification of TTS among selected patients initially presenting with ACS, a ratio more clinically useful in the setting of NSTEMI.

Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (p-value = 2.63 × 10-25). PGS000012 was associated with a modest increase in CAD risk by 2.2% (p-value = 9.58 × 10-4). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.