The effect of probiotic consumption on lipid profile, glycemic index, inflammatory markers, and liver function in NAFLD patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND-AIM: Non-alcoholic fatty liver disease (NAFLD1) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients. METHODS: We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD2) with a 95 % confidence interval (CI3). Publication bias and heterogeneity were evaluated in eligible studies. RESULTS: Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (-1.419, -0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR4) [SMD -0.596; 95 % CI (-1.071, -0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (-2.121, -0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.

Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery.

The 21st century is characterized by an increasing incidence and prevalence of obesity and the burden of its associated comorbidities, especially cardiometabolic diseases, which are reaching pandemic proportions. In the late '90s, the "black box" of adipose tissue and energy homeostasis was opened with the discovery of leptin, transforming the adipose tissue from an "inert fat-storage organ" to the largest human endocrine organ and creating the basis on which more intensified research efforts to elucidate the pathogenesis of obesity and develop novel treatments were based upon. Even though leptin was eventually not proven to be the "standalone magic bullet" for the treatment of common/polygenic obesity, it has been successful in the treatment of monogenic obesity syndromes. Additionally, it shifted the paradigm of treating obesity from a condition due to "lack of willpower" to a disease due to distinct underlying biological mechanisms for which specific pharmacotherapies would be needed in addition to lifestyle modification. Subsequently, the melanocortin pathway proved to be an equally valuable pathway for the pharmacotherapy of obesity. Melanocortin receptor agonists have recently been approved for treating certain types of syndromic obesity. Other molecules- such as incretins, implicated in energy and glucose homeostasis- are secreted by the gastrointestinal tract. Glucagon-like peptide 1 (GLP-1) is the most prominent one, with GLP-1 analogs approved for common/polygenic obesity. Unimolecular combinations with other incretins, e.g., GLP-1 with gastric inhibitory polypeptide and/or glucagon, are expected to be approved soon as more effective pharmacotherapies for obesity and its comorbidities. Unimolecular combinations with other compounds and small molecules activating the receptors of these molecules are currently under investigation as promising future pharmacotherapies. Moreover, metabolic and bariatric surgery has also demonstrated impressive results, especially in the case of morbid obesity. Consequently, this broadening therapeutic armamentarium calls for a well-thought-after and well-coordinated multidisciplinary approach, for instance, through cardiometabolic expertise centers, that would ideally address effectively and cost-effectively obesity and its comorbidities, providing tangible benefits to large segments of the population.

Ferroptosis, a new pathogenetic mechanism in cardiometabolic diseases and cancer: Is there a role for statin therapy?

One of the newly recognized types of cell death is ferroptosis which is related to the accumulation of iron and lipid-reactive oxygen species. Ferroptosis is considered a programmed cell death with a different mechanism from apoptosis, necrosis, and autophagy. Emerging evidence suggests that ferroptosis may occur in the context of cardiovascular disease (CVD), cancer, neurodegenerative diseases, and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line therapy for dyslipidemia. The suppression of the HMG-CoA reductase by statins leads to decreased expression of glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation, which in turn results in lipid ROS production and induction of ferroptosis. Experimental data suggest that statins may act as anti-cancer drugs by enhancing tumor cells' ferroptosis. In contrast, statins have also been reported to mitigate ferroptosis in animal models of myocardial ischemia-reperfusion and heart failure. This mini-review presents statin effects on the ferroptosis pathway, based on up-to-date in vivo and in vitro research. Furthermore, the potential impact of these effects on cardiometabolic diseases (e.g., CVD and NAFLD) and cancer is briefly discussed. Overall, there is a need for future studies focusing on statin-induced changes in ferroptosis as a therapeutic approach to such diseases.

Nutrient Intake and Risk Factors for Metabolic Syndrome in Christian Orthodox Church Religious Fasters.

OBJECTIVE: Studies regarding health effects of religious fasting have been increased during the last decade. Our aim was to investigate the impact of adherence to the periodic Christian Orthodox Church (COC) fasting on nutrient intake, body composition, and risk factors for metabolic syndrome (MetS). METHODS: Four-hundred individuals aged 42.6 ± 17.0 years participated in this cross-sectional study. Two-hundred subjects followed the COC fasting since childhood or at least the last twelve consecutive years, and two-hundred subjects did not follow the COC fasting regimes or any other restrictive dietary pattern. Socioeconomic data, lifestyle habits, and physical activity data were collected. Nutritional assessment was performed via two 24 h recalls and a food frequency questionnaire. Anthropometric data and biochemical parameters were also measured. RESULTS: Fasters had a significantly lower daily intake of calories (1547 vs. 1662 kcals, p = 0.009), protein (52 vs. 59 g, p = 0.001), fat (82 vs. 89 g, p = 0.012), and cholesterol (147 vs. 178 g, p = 0.001) compared with non-fasters. Furthermore, fasters reported a healthier way of living, with lower rates of smoking and alcohol consumption (p < 0.001 and 0.002, respectively). Insulin and magnesium levels were significantly higher, whereas levels of urea, transaminases, glucose, and phosphorus were significantly lower, as was DBP in fasters versus non-fasters. Furthermore, MetS prevalence was non-significantly higher in non-faster compared with fasters. CONCLUSION: During a non-fasting period, individuals following the COC fasting recommendations reported lower intake of calories, protein, fat, and cholesterol compared with non-fasters. Fasters tended to have a healthier lifestyle pattern and a lower risk for MetS versus non-fasters. Some biochemical parameters also significantly differed between the two study groups. Further research is warranted to establish the long-term clinical impact of these findings.

Real world data from a multi-centre study on the effects of cilostazol on pain symptoms and walking distance in patients with peripheral arterial disease.

OBJECTIVE: to assess the effects of cilostazol on pain-free walking distance in PAD patients with IC at 3 and 6 months in a real world, prospective, observational study. We included 1015 PAD patients presenting with IC (71.3% men, 93.5% white, mean age 69.2 ± 8.7 years). Patients were followed up for 6 months by their physicians. RESULTS: Cilostazol significantly increased pain-free walking distance by a median of 285 and 387 m at 3 and 6 months, respectively (p < 0.01 for all comparisons). This effect was significant for patients 50-74 years (but not for those aged ≥ 75 years) and independent of smoking status, changes in physical activity, comorbidities and concomitant medication for PAD (i.e., acetylsalicylic acid and clopidogrel). Furthermore, significant reductions were observed in systolic (from 139 ± 16 to 133 ± 14 mmHg; p < 0.001) and diastolic blood pressure (from 84 ± 9 mmHg to 80 ± 10 mmHg; p < 0.001). Smoking cessation and increased physical activity were reported by the majority of participants. In conclusion, cilostazol was shown to safely decrease pain symptoms and improve pain-free walking in PAD patients with IC in a real world setting. Benefits also occurred in terms of BP and lifestyle changes.

Mediterranean Diet and Obesity-related Disorders: What is the Evidence?

PURPOSE OF REVIEW: Obesity is a chronic disease, a major public health problem due to its association with non-communicable diseases and all-cause mortality. Indeed, people with obesity are at increased risk for a variety of obesity-related disorders including hypertension, dyslipidemia, type 2 diabetes mellitus, cardiovascular disease, and several cancers. Many popular diets with very different macronutrient composition, including the Mediterranean diet (MD), have been used, proposed, and studied for prevention and management of obesity. In particular, MD has been the subject of countless studies over the years and now boasts a large body of scientific literature. In this review, we aimed to update current knowledge by summarizing the most recent evidence on the effect of MD on obesity and obesity-related disorders. RECENT FINDINGS: The negative effects of obesity are partly reversed by substantial weight loss that can be achieved with MD, especially when low-calorie and in combination with adequate physical activity. In addition, the composition of MD has been correlated with an excellent effect on reducing dyslipidemia. It also positively modulates the gut microbiota and immune system, significantly decreasing inflammatory mediators, a common ground for many obesity-related disorders. People with obesity are at increased risk for a variety of medical disorders including hypertension, dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease. Therefore, there is an inevitable need for measures to manage obesity and its related disorders. At this point, MD has been proposed as a valuable nutritional intervention. It is characterized by a high consumption of vegetables, fruit, nuts, cereals, whole grains, and extra virgin olive oil, as well as a moderate consumption of fish and poultry, and a limited intake of sweets, red meat, and dairy products. MD proves to be the healthiest dietary pattern available to tackle obesity and prevent several non-communicable diseases, including cardiovascular disease and type 2 diabetes.

Effect of Serum Lipid Profile on the Risk of Breast Cancer: Systematic Review and Meta-Analysis of 1,628,871 Women.

Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile and breast cancer risk. Databases such as PubMed, EMBASE, and Web of Sciences were searched up to the end of January 2021 using certain MeSH and non-MeSH keywords and combinations to extract related published articles. Twenty-six prospective studies involving 1,628,871 women, of whom 36,590 were diagnosed with breast cancer during the follow-up period met the inclusion criteria. A negative and significant association was found between the HDL-C level and the risk of breast cancer (relative risk (RR): 0.85, 95% CI: 0.72-0.99, I2: 67.6%, p = 0.04). In contrast, TG (RR: 1.02, 95% CI: 0.91-1.13, I2: 54.2%, p = 0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90-1.06, I2: 67.2%, p = 0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70-1.30, I2: 83.5%, p = 0.78) and LDL-C (RR: 0.93, 95% CI: 0.79-1.09, I2: 0%, p = 0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, breast cancer risk was positively correlated with TC (RR: 1.05, 95% CI: 1.01-1.10). Similarly, TG was significantly related to breast cancer development after adjustment for baseline lipids (RR: 0.92, 95% CI: 0.85-0.99) and race (any races mentioned in each study) (RR: 1.80, 95% CI: 1.22-2.65). In the present meta-analysis, HDL-C was inversely related to breast cancer risk. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence that low HDL-C is related to an increased risk for this type of malignancy.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Trend of perceived quality of life and functional capacity in outpatients with chronic heart failure and in treatment with sacubitril/valsartan: a real-life experience.

BACKGROUND: Despite the use of optimal medical therapy, heart failure and reduced left ventricular ejection fraction (HFrEF) remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with HFrEF. The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. METHODS: We enrolled 37 patients (63±10 years old, 76% men) who underwent a total of one-year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular, NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. RESULTS: We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NT-ProBNP, BNP and NYHA class. However, analyzing the ∆% of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). CONCLUSIONS: Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Contrast-induced Nephropathy in Non-cardiac Vascular Procedures, A Narrative Review: Part 1.

Contrast-induced Nephropathy (CIN) is animportant complication of iodinated Contrast Medium (CM) administration, being associated with both short- and long-term adverse outcomes (e.g., cardiorenal events, longer hospital stay and mortality). CIN has been mainly studied in relation to cardiac procedures but it can also occur following non-cardiac vascular interventions. This is Part 1 of a narrative review summarizing the available literature on CIN after non-cardiac vascular diagnostic or therapeutic procedures for aortic aneurysm and carotid stenosis. We discuss the definition, pathophysiology, incidence, risk factors, biomarkers and consequences of CIN in these settings, as well as preventive strategies and alternatives to limit iodinated CM use. Physicians and vascular surgeons should be aware of CM-related adverse events and the potential strategies to avoid it. Clearly, more research in this important field is required.

Contrast-induced Nephropathy in Non-cardiac Vascular Procedures, A Narrative Review: Part 2.

This is Part 2 of a narrative review summarizing the literature on CIN after non-cardiac vascular diagnostic or therapeutic procedures, focusing on Peripheral Artery Disease (PAD) and Renal Artery Stenosis (RAS). Part 1 discussed CIN in relation to aortic aneurysms and carotid stenosis. We comment on the incidence, biomarkers, risk factors and consequences of CIN in patients with PAD or RAS, as well as on strategies to prevent CIN. Future perspectives in the field of CIN in relation to non-cardiac vascular procedures are also considered.

Management of patients with asymptomatic carotid stenosis may need to be individualized: a multidisciplinary call for action. Republication of J Stroke 2021;23:202-212.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Olive Oil Intake and Cardiovascular Disease Prevention: "Seek and You Shall Find".

PURPOSE OF REVIEW: The present narrative review focuses on the up-to-date clinical data on the correlations between olive oil consumption and cardiovascular (CV) diseases (i.e., CHD, stroke, and peripheral artery disease). RECENT FINDINGS: Olive oil contains monounsaturated fats, several antioxidant phenols, and other micronutrients that mediate CV-protective effects via improvements in oxidative stress, endothelial dysfunction, inflammation, thrombosis, blood pressure, and lipid and carbohydrate metabolism. High consumption of olive oil, and in particular the extra-virgin, which is rich in phenolic antioxidants, has been suggested to prevent against coronary heart disease (CHD). The olive oil-induced cardioprotection was further supported by the findings of a very recent analysis of 2 large US prospective cohort studies showing that a higher olive oil intake was related to a lower risk of CV morbidity and mortality after 24 years of follow-up and that replacement of dairy fat, margarine, butter, or mayonnaise with the equivalent amount of olive oil significantly reduced CV risk. There is evidence for associations between olive oil consumption and lower risk for CV diseases. Both health policy makers and physicians should be aware of these associations and thus promote the intake of olive oil in both primary and secondary prevention settings to minimize individual's CV risk.

Α higher ratio of serum uric acid to serum creatinine could predict the risk of total and cause specific mortality- insight from a US national survey.

INTRODUCTION: The link between serum uric acid to serum creatinine ratio (SUA/SCr) and mortality has not been studied yet. METHODS: We prospectively evaluated the association between SUA/SCr and risk of total and cause specific [cardiovascular disease (CVD) and cancer] mortality by applying on the National Health and Nutrition Examination Surveys (NHANES, 1999-2010). Vital status through December 31, 2011 was ascertained. Adjusted Cox proportional hazard regression models were performed to determine the links between SUA/SCr and mortality. RESULTS: Overall, 20,209 individuals were included (mean age = 47.5 years, 48.9% men) and 3523 deaths occurred during the 76.4 months of follow-up. In a fully adjusted model, individuals in the fourth (Q4) and third (Q3) quartile of SUA/SCr had a 44 and 35% greater risk of total mortality [risk ratio (RR): 1.44 (95% confidence interval, 95%CI: 1.05-1.98) and 1.35 (1.10-1.66), respectively], as well as a 69 and 47% higher risk of CVD death [RR: 1.69 (1.09-2.62) and 1.47 (1.14-1.89), respectively] compared with the lowest (Q1) quartile. With regard to SUA/SCr and cancer mortality, a significant association was found only between participants in Q4 and those in Q1 [RR: 1.12 (1.06-1.19)] in the partially adjusted model, whereas this relationship became non-significant after further adjustments [RR: 1.15 (0.96-1.39)]. CONCLUSIONS: This is the first time that SUA/SCr has been associated with total and cause specific mortality in a large, representative sample of US adults. Further studies are needed to confirm these findings and establish their clinical implications.

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications.

Mitochondria provide energy to the cell during aerobic respiration by supplying ~95% of the adenosine triphosphate (ATP) molecules via oxidative phosphorylation. These organelles have various other functions, all carried out by numerous proteins, with the majority of them being encoded by nuclear DNA (nDNA). Mitochondria occupy ~1/3 of the volume of myocardial cells in adults, and function at levels of high-efficiency to promptly meet the energy requirements of the myocardial contractile units. Mitochondria have their own DNA (mtDNA), which contains 37 genes and is maternally inherited. Over the last several years, a variety of functions of these organelles have been discovered and this has led to a growing interest in their involvement in various diseases, including cardiovascular (CV) diseases. Mitochondrial dysfunction relates to the status where mitochondria cannot meet the demands of a cell for ATP and there is an enhanced formation of reactive-oxygen species. This dysfunction may occur as a result of mtDNA and/or nDNA mutations, but also as a response to aging and various disease and environmental stresses, leading to the development of cardiomyopathies and other CV diseases. Designing mitochondria-targeted therapeutic strategies aiming to maintain or restore mitochondrial function has been a great challenge as a result of variable responses according to the etiology of the disorder. There have been several preclinical data on such therapies, but clinical studies are scarce. A major challenge relates to the techniques needed to eclectically deliver the therapeutic agents to cardiac tissues and to damaged mitochondria for successful clinical outcomes. All these issues and progress made over the last several years are herein reviewed.

Diabetes Mellitus and Chronic Obstructive Pulmonary Disease: An Overview.

Chronic obstructive pulmonary disease (COPD) is a common disease with an increasing prevalence, characterised by persistent respiratory symptoms and airflow limitation. Apart from cigarette smoking, certain occupational and environmental exposures, low socioeconomic status and genetic factors may contribute to the pathogenesis of COPD. Comorbidities, e. g. diabetes mellitus (DM), can negatively affect quality of life, COPD outcomes and cardiovascular risk. The present narrative review considers the potential links between COPD and DM, such as systemic inflammation, oxidative stress, hypoxaemia and hyperglycaemia. The effects of antidiabetic drugs on lung function and COPD outcomes, as well as the possibility of common therapeutic modalities are also briefly considered. Further research is needed in this field to elucidate these relationships as well as their potential clinical implications in daily practice.

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study.

AIM: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). PATIENTS AND METHODS: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. RESULTS: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. CONCLUSIONS: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.

A Greater Flavonoid Intake Is Associated with Lower Total and Cause-Specific Mortality: A Meta-Analysis of Cohort Studies.

Introduction: The links between flavonoid intake and mortality were previously evaluated in epidemiological studies. The aim of the present study was to perform a systematic review and meta-analysis of cohort studies evaluating the link of flavonoid consumption with total and cause-specific mortality. Methods: Prospective cohort studies reporting flavonoid intake and mortality data published up to 30th April 2019 (without language restriction) were searched using PubMed, Scopus and EMBASE database. Generic inverse variance methods and random effects models were used to synthesize pooled and quantitative data. Sensitivity analysis was also performed by a leave-one-out method. Results: Overall, 16 articles met the inclusion criteria (nine studies were performed in Europe, five in the USA, one in Asia and one in Oceania); a total of 462,194 participants (all adults aged >19 years) with 23,473 mortality cases were included in the final analysis. The duration of follow-up ranged from 4.8 to 28 years. Most of the studies assessed flavonoid intake using food frequency questionnaires, whereas four studies used interviews and 1 study used 4-day food records. The meta-analysis showed that flavonoid consumption was inversely and significantly associated with total (relative risk (RR): 0.87, 95% confidence interval (CI) = 0.77-0.99) and cardiovascular disease mortality risk (RR: 0.85, 95%CI = 0.75-0.97), but not cancer (0.86, 95%CI = 0.65-1.14) mortality risk. These findings remained robust in sensitivity analyses. Conclusions: The present findings highlight the potential protective role of flavonoids against total and cause-specific mortality. These results support the recommendations for flavonoid-rich foods intake to prevent chronic diseases.