Phenotypes of Polish primary care patients using hierarchical clustering: Exploring the risk of mortality in the LIPIDOGEN2015 study cohort.

BACKGROUND: Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. METHODS: The baseline cohort of the LIPIDOGEN2015 sub-study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all-cause mortality. RESULTS: A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow-up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non-overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all-cause mortality (HR 3.87, 95% CI: 1.24-15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all-cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3. CONCLUSION: Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Protective Effects of Curcumin on Endothelium: An Updated Review.

Endothelial dysfunction is the common early stage of most cardiovascular afflictions. The endothelium is considered the main mediator of vascular homeostasis via its vasodilator, anti-inflammatory and anticoagulant properties. Among the different endothelial-derived mediators, nitric oxide is produced by nitric oxide synthase and has a critical role in regulating endothelial function. Physiological and pathological processes such as aging and diabetes mellitus are associated with disturbances of endothelial function which, at least at the earliest stage, can be reversed by lifestyle and pharmacological intervention to reduce the risk of incident cardiovascular diseases. Among dietary strategies, curcumin is a cheap and safe nutraceutical polyphenol with proven antioxidant and anti-inflammatory properties. Given the important role of such processes in the development of endothelium dysfunction, a role for curcumin in the prevention or treatment of this condition has been hypothesized. This review summarizes the available literature on the beneficial role of curcumin on vascular endothelial function.

May Measurement Month 2018: an analysis of blood pressure screening campaign results from Poland.

Hypertension remains the most important cardiovascular risk factor in Poland. May Measurement Month is a global initiative organized by the International Society of Hypertension aimed at raising awareness of hypertension and the need for blood pressure (BP) screening and demonstrating the potential of the opportunistic BP measurements. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in 146 sites in May 2018. Blood pressure was measured in 6450 subjects (mean age: 41 ± 15 years; 59% females). After multiple imputation, the age and sex standardized systolic and diastolic BP was 126.7/78.4 mmHg in the whole analysed group, 132.8/81.3 mmHg in subjects taking antihypertensive drugs, and 125.7/78.0 mmHg in those not taking any antihypertensive drugs. After multiple imputation, the proportions of subjects with high BP (systolic ≥140 mmHg or diastolic ≥90 mmHg or on treatment for raised BP) were 22.2% in the whole analysed group, 39.2% in subjects taking antihypertensive drugs, and 18.6% those not taking any antihypertensive drugs. Overall, hypertension was present in 32.8% of participants, among them 38.7% were not aware of the disease, 53.1% were taking antihypertensive drugs, and 32.3% had BP controlled to target (<140/90 mmHg). Blood pressure was increasing with increasing body mass index and alcohol intake. Smokers and project participants with diabetes had increased average BP. In conclusion, this project provides additional evidence for a considerable potential for further reduction of cardiovascular risk through improvement in detection and treatment of hypertension in Poland.

Adiposity May Moderate the Link Between Choline Intake and Non-alcoholic Fatty Liver Disease.

Background: In animal models, histological and biochemical changes are observed in response to choline deficiency. It is unclear whether dietary choline is linked to non-alcoholic fatty liver disease (NAFLD). Objective: We examined the link among liver tests, fatty liver index (FLI), and choline consumption. Furthermore, we evaluated the impact of adiposity on this association. Method: The National Health and Nutrition Examination Survey (NHANES) was used to obtain data on choline intake and liver function biomarkers. Masked variance and weighting methodology were performed to account for the complex NHANES data. Results: Of the 20,643 participants, 46.8% were men and 45.6% had NAFLD (defined as United States FLI ≥30). In a fully adjusted model (for demographic, dietary, and clinical factors), a significant negative association was found between FLI and choline consumption (ß = -0.206, p < 0.001). Participants in the highest quartile (Q4) of choline intake had a 14% lower risk of NAFLD compared with those in the first quartile (Q1). This link was stronger for postmenopausal women; women in Q4 had a 26% lower risk of NAFLD compared with those in Q1. Body mass index (BMI) strongly moderated the link between FLI and choline intake. For example, when choline consumption increased from low (272 mg/d) to high (356 mg/d), FLI decreased from 79.3 to 74.1 in the low BMI category (mean BMI = 22.1 kg/m2) and from 32.1 to 20.6 in the high BMI category (mean BMI =35.9 kg/m2). Conclusions: Our results suggest the presence of a reverse significant association between choline intake and risk of NAFLD. Furthermore, BMI was shown to mediate this relationship since changes in FLI, in relation to choline consumption, were more pronounced in participants with a higher BMI.

Modulation of heat shock proteins by statins.

Heat shock proteins (HSP or stress proteins) are intracellular molecules that participate in physiological cell metabolism and growth, although they are known to be involved in many stress conditions. Statins inhibit the action of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), which is important in the synthesis of cholesterol and essential isoprenoid intermediates, thereby lowering circulating low-density lipoprotein cholesterol (LDL), a major risk factor for cardiovascular disease (CVD). This review provides new insights into the mechanisms of action of statins in the regulation of HSPs. A better understanding of this involvement can help in development of new and more effective treatment strategies for CVD.

The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.

The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. METHODS: ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and <80, and ≥80 mL/min, and an exploratory ≥95-mL/min analysis. RESULTS: A total of 1,095 subjects were randomized to edoxaban and 1,104 to enoxaparin-warfarin. Mean age was 64.3±10 and 64.2±11 years. Mean time in therapeutic range was progressively lower with reducing CrCl strata, being 66.8% in those with CrCl >30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. CONCLUSION: Given the small number of events in ENSURE-AF, no effect of renal (dys)function was demonstrated in comparing edoxaban to enoxaparin-warfarin for cardioversion; efficacy and safety of edoxaban remained consistent even in patients with normal or supranormal renal function.

IMPROVE-IT: what have we learned?

PURPOSE OF REVIEW: Recent studies and dyslipidemia treatment guidelines indicate that combination lipid-lowering therapy is frequently needed and its use has increased in recent years. Ezetimibe and simvastatin as a fixed dose is an efficacious treatment choice based on positive results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). In this review, we discuss recent controversies surrounding ezetimibe and provide clinical perspective on the results of the IMPROVE-IT study. RECENT FINDINGS: IMPROVE-IT is the first trial that demonstrates a significant clinical benefit of a nonstatin hypolipidemic agent (ezetimibe) used in combination with statin (simvastatin) therapy in patients who have experienced an acute coronary syndrome. For almost a decade, the use of ezetimibe was limited by a relative lack of definitive evidence. However, the most recent Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound study showed greater coronary plaque regression by statin/ezetimibe combination compared with statin monotherapy. The results of the IMPROVE-IT trial are fostering new debate about the value of adjunctive low-density lipoprotein cholesterol lowering over and above a statin. SUMMARY: Ezetimibe/simvastatin combination, either as a single pill or as the combined use of the individual compounds, represents a well-tolerated and efficacious choice for dyslipidemia treatment in high-risk subjects, including patients with diabetes. Limited additional risk for adverse events compared with simvastatin monotherapy is observed, and an individualized, patient-centered approach to therapy is recommended.

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent.

Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk. D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

Lipids, blood pressure and kidney update 2014.

This paper is an effort to review all the most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2014. Irrespective of advances, the options for improving simultaneous hypercholesterolemia and hypertension management (as well as its complication - chronic kidney disease) remain a problem. Recommending hypolidemic, hypotensive and kidney disease drugs to obtain therapy targets in cardiovascular, diabetic, elderly and kidney disease (=high risk) patients might strengthen risk factor control, improve compliance and the therapy efficacy, and in the consequence reduce the risk of cardiovascular events and mortality rate. That is why the authors have decided to summary and discuss the recent scientific achievements in the field of lipid, blood pressure and kidney.

Nutrition, Nutraceuticals and Bioactive Compounds in the Prevention and Fight against Inflammation.

Chronic low-grade systemic inflammation is a key factor involved in the pathogenesis of many diseases and their complications (Figure 1) [...].

Is COVID-19 another case of the obesity paradox? Results from an international ecological study on behalf of the REPROGRAM Consortium Obesity study group.

Introduction: Obesity has emerged as one of the major risk factors of severe morbidity and cause-specific mortality among severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected individuals. Patients with obesity also have overlapping cardiovascular diseases and diabetes, which make them increasingly vulnerable. This novel ecological study examines the impact of obesity and/or body mass index (BMI) on rates of population-adjusted cases and deaths due to coronavirus disease 2019 (COVID-19). Material and methods: Publicly available datasets were used to obtain relevant data on COVID-19, obesity and ecological variables. Group-wise comparisons and multivariate logistic regression analyses were performed. The receiver operating characteristic curve (ROC) was plotted to compute the area under the curve. Results: We found that male BMI is an independent predictor of cause-specific (COVID-19) mortality, and not of the caseload per million population. Countries with obesity rates of 20-30% had a significantly higher (approximately double) number of deaths per million population to both those in < 20% and > 30% slabs. We postulate that there may be a U-shaped paradoxical relationship between obesity and COVID-19 with the cause-specific mortality burden more pronounced in the countries with 20-30% obesity rates. These findings are novel along with the methodological approach of doing ecological analyses on country-wide data from publicly available sources. Conclusions: We anticipate, in light of our findings, that appropriate targeted public health approaches or campaigns could be developed to minimize the risk and cause-specific morbidity burden due to COVID-19 in countries with nationwide obesity rates of 20-30%.

Evaluation of the efficacy and safety of bempedoic acid in women and men: Pooled analyses from phase 3 trials.

BACKGROUND AND AIMS: Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid. METHODS: Patients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) "on statins" and 2) "low-dose or no statin". Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex. RESULTS: Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p ≤ 0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (-21.2% vs. -17.4%; p = 0.044), non-HDL-C (-17.3% vs. -12.1%; p = 0.003), TC (-13.8% vs. -10.5%; p = 0.012), and Apo B (-16.0% vs. -11.3%; p = 0.004) in the ASCVD and/or HeFH on statins pool. Women had similar reductions to men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes. CONCLUSIONS: In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.

Bempedoic acid lowers high-sensitivity C-reactive protein and low-density lipoprotein cholesterol: Analysis of pooled data from four phase 3 clinical trials.

BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hsCRP), a marker for atherosclerotic cardiovascular disease risk, is reduced by bempedoic acid. We assessed the relationship between changes in low-density lipoprotein cholesterol (LDL-C) and hsCRP in relation to baseline statin use. METHODS: Pooled data from four phase 3 trials (patients on maximally tolerated statins [Pool 1] and patients receiving no or low-dose statins [Pool 2]) were used to determine the proportion of patients with baseline hsCRP ≥2 mg/L who achieved hsCRP <2 mg/L at week 12. The percentage of patients who achieved hsCRP <2 mg/L and guideline-recommended LDL-C (Pool 1, <70 mg/dL; Pool 2, <100 mg/dL) was determined for patients on statins in Pool 1 and those not on statins in Pool 2, as was the correlation between percent changes in hsCRP and LDL-C. RESULTS: Overall, 38.7% in Pool 1 and 40.7% in Pool 2 with baseline hsCRP ≥2 mg/L achieved hsCRP <2 mg/L with bempedoic acid, with little effect from background statin. Among patients taking a statin in Pool 1 or not taking a statin in Pool 2, 68.6% and 62.4% achieved hsCRP <2 mg/L. Both hsCRP <2 mg/L and United States guideline-recommended LDL-C were achieved more often with bempedoic acid vs. placebo (20.8% vs. 4.3%, respectively, in Pool 1 and 32.0% vs. 5.3%, in Pool 2). Changes in hsCRP and LDL-C were only weakly correlated (Pool 1, r = 0.112; Pool 2, r = 0.173). CONCLUSIONS: Bempedoic acid significantly reduced hsCRP irrespective of background statin therapy; the effect was largely independent of LDL-C lowering.

De-escalation of antiplatelet therapy in patients with coronary artery disease: Time to change our strategy?

Dual antiplatelet therapy (DAPT) is the gold standard after acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Because local and systemic ischemic complications can occur particularly in the early phase (i.e. 1-3 months) after ACS or PCI, the synergistic platelet inhibition of aspirin and a P2Y12 inhibitor is of the utmost importance in this early phase. Moreover, the use of the more potent P2Y12 inhibitors prasugrel and ticagrelor have shown to further reduce the incidence of ischemic events compared to clopidogrel after an ACS. On the other hand, prolonged and potent antiplatelet therapy are inevitably associated with increased bleeding, which unlike thrombotic risk, tends to be stable over time and may outweigh the benefit of reducing ischemic events in these patients. The duration and composition of antiplatelet therapy remains a topic of debate in cardiology due to competing ischemic and bleeding risks, with guidelines and recommendations considerably evolving in the past years. An emerging strategy, called "de-escalation", consisting in the administration of a less intense antithrombotic therapy after a short course of standard DAPT, has shown to reduce bleeding without any trade-off in ischemic events. De-escalation may be achieved with different antithrombotic strategies and can be either unguided or guided by platelet function or genetic testing. The aim of this review is to summarize the evidence and provide practical recommendations on the use of different de-escalation strategies in patients with ACS and CCS.

Prevention of sudden cardiac death in patients with chronic kidney disease.

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients' prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.

Protective role of nutraceuticals against myocarditis.

Myocarditis is an inflammatory disease of the myocardium that mostly affects young adults. The disease is commonly caused by viral infection, medications, autoimmune disorders, and inflammatory conditions. Nearly 50% of the cases of myocarditis are due to post-viral immune response in a setting of an identifiable or non-identifiable infection. The clinical manifestation is nonspecific ranging from asymptomatic courses to sudden death in infants and young patients. This review describes the properties of phytochemicals as plant-derived active ingredients which can be used in the prevention and treatment of myocarditis and its associated risk factors. Meanwhile, it has illustrated epidemiological analyses, mechanism of action, and the metabolism of phytochemicals in animal and human clinical trials. We also mentioned the precise mechanism of action by which phytochemicals elicit their anti-viral, anti-inflammatory, antioxidant, and immunomodulatory effects and how they regulate signal transduction pathways. Nevertheless, comprehensive clinical trials are required to study the properties of phytochemicals in vivo, in vitro, and in silico for a proper management of myocarditis. Our findings indicate that phytochemicals function as potent adjunctive therapeutic drugs in myocarditis and its related complications.

Killing the Culprit: Pharmacological Solutions to Get Rid of Cholesterol Crystals.

Cholesterol crystals (CCs) play a key role in the pathophysiology of cardiovascular diseases (CVD) via triggering inflammation, plaque formation and subsequently plaque rupture. Although statins can stabilize plaques via calcification and alteration of the lipid composition within plaques, there is still a high residual risk of CVD events among statins users. Several studies have tried to blunt the detrimental effects of cholesterol crystals by pharmacological interventions. Cyclodexterins (CDs) and other nanoformulations, including polymers of CDs and liposomes, have the ability to dissolve CCs in vitro and in vivo. CDs were the first in their class that entered clinical trials and showed promising results, though their ototoxicity outweighed their benefits. Moreover, small molecules with structural similarity to cholesterol may also perturb cholesterol-cholesterol interactions and prevent from expansion of 2D crystalline domains to large 3D CCs. The results from ethyl eicosapentaenoic acid and ursodeoxycholic acid were encouraging and worth further consideration. In this review, the significance of CCs in pathogenesis of CVD is discussed and pharmacological agents with the ability to dissolve CCs or prevent from CCs formation are introduced.

Effects of Implementing Personalized Health Education in Ambulatory Care on Cardiovascular Risk Factors, Compliance and Satisfaction with Treatment.

Aim and Methods: Data from the CARDIOPLUS study (a prospective, multicenter, non-interventional study, which was conducted among patients and physicians from ambulatory patient care in Poland) were used to assess whether primary care behavioral counseling interventions to improve diet, increase physical activity, stop smoking and reduce alcohol consumption improve outcomes associated with cardiovascular (CVD) risk factors, metabolic parameters, compliance and satisfaction with treatment in adults. The study was carried out throughout Poland in the period from July to December 2019. Results: The study included 8667 patients­49% women and 51% men aged (63 ± 11 years)­and 862 physician-researchers. At the 3-month follow-up, there was a significant reduction in body weight (p = 0.008); reduction of peripheral arterial pressure, both systolic (p < 0.001) and diastolic (p < 0.001); reduction in total cholesterol levels (p < 0.001), triglycerides (p < 0.001), and LDL cholesterol (p < 0.001). The percentage of respondents who fully complied with the doctor's recommendations increased significantly. The respondents assessed their own satisfaction with the implemented treatment as higher (by about 20%). Conclusions: As a result of pro-health education in the field of lifestyle modifications, a significant reduction of risk factors for cardiovascular diseases, as well as improved compliance and satisfaction with pharmacological treatment, was observed. Thus, appropriate personalized advice on lifestyle habits should be given to each examinee in a positive, systematic way following the periodic health check-ups in order to reduce the person's risk and improve the effectiveness of the treatment.

Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia.

Cachexia, a multifactorial and often irreversible wasting syndrome, is often associated with the final phase of several chronic disorders. Although cachexia is characterized by skeletal muscle wasting and adipose tissue loss, it is a syndrome affecting different organs, which ultimately results in systemic complications and impaired quality of life. The pathogenesis and underlying molecular mechanisms of cachexia are not fully understood, and currently there are no effective standard treatments or approved drug therapies to completely reverse cachexia. Moreover, adequate nutritional interventions alone cannot significantly improve cachexia. Other approaches to ameliorate cachexia are urgently needed, and thus, the role of medicinal plants has received considerable importance in this respect due to their beneficial health properties. Increasing evidence indicates great potential of medicinal plants and their phytochemicals as an alternative and promising treatment strategy to reduce the symptoms of many diseases including cachexia. This article reviews the current status of cachexia, the molecular mechanisms of primary events driving cachexia, and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action, which may hold promise as an alternative treatment modality for the management of cachexia. Based on our review of various in vitro and in vivo models of cachexia, we would conclude that phytochemicals may have therapeutic potential to attenuate cachexia, although clinical trials are required to unequivocally confirm this premise.