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The rise in prevalence of childhood obesity is paralleled by an increase in obesity-related metabolic complications, which add significantly to the population burden of cardiovascular morbidity in the long term. Early detection of obesity-related metabolic complications through appropriate screening strategies forms a crucial aspect of obesity management. We performed a scoping review of international and national guidelines on the management of pediatric obesity to evaluate the recommendations on screening for metabolic complications, namely, hypertension, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Thirty guidelines were included, 23 (76.7%) of which had some guidance on screening for metabolic complications. However, there were significant variations in the extent and details of recommendations for screening for these metabolic complications. There has been no consensus on the body mass index (BMI) thresholds, age of onset, frequency, and screening tests recommended for detecting hypertension, diabetes, dyslipidemia, and non-alcoholic fatty liver disease between guidelines. These variations did not appear to be polarized based on geographical location or population ethnicity. We provide our recommendations on metabolic screening based on the strength of evidence in the guidelines, also incorporating recommendations from key childhood hypertension, diabetes, and lipid guidelines. Appropriate implementation of screening strategies is crucial to improve detection of metabolic complications, to allow for earlier or more intensified interventions for affected children with obesity., (© 2022 World Obesity Federation.)

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group., (© 2022. The Author(s).)

Background: Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population., Methods: We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association., Results: Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55-2.58) and over 60 years (HR: 3.36, 95% CI: 2.47-4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01-1.56), diabetes (HR: 1.46, 95% CI: 1.06-2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07-1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12-1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05)., Conclusion: A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation., (© 2022. The Author(s).)

Background: Diabetes mellitus (DM) is a major public health concern. This study aims to determine frequency, pattern, and potential determinants of dyslipidemia among adults with type 2 DM (T2DM) at Somalia's only diabetes outpatient clinic., Methods: Five hundred twenty-nine consecutive patients with T2DM who applied to our outpatient clinic between January 2020 and June 2020 were included in this cross-sectional hospital-based study. Demographic characteristics of participants, including lipid panel, were extracted from the registry system. Correlation analysis was performed between lipid profile and related parameters. Multivariate binary logistic regression models were used to identify independent determinants of dyslipidemia for further analysis., Results: The overall population's mean age was 51.9 ± 12.2 years, with 177 (33.5%) males. Total and atherogenic dyslipidemias were found in 92.8% and 24.8%, respectively. The most common isolated pattern of dyslipidemia was high non-high-density lipoprotein cholesterol (non-HDL-C) (82.8%), followed by high low-density lipoprotein cholesterol (LDL-C) (72.6%), high total cholesterol (TC) (54.3%), and low HDL-C (48.3%). Females were found to have a higher prevalence of high TC (63.4% vs. 54.2%, p = 0.043) and lower HDL-C (57.4% vs. 46.3%, p = 0.016). High LDL-C with low HDL-C was the most common pattern among combined type dyslipidemias (18.1%), followed by high LDL-C with high triglyceride (TG) (17.8%), as well as low TG with low HDL-C (3.6%). Females had a higher proportion of high LDL-C with low HDL-C than males (20.3% vs. 13.6%, p = 0.036). Age, gender, body mass index, central obesity, spot urinary proteinuria, fasting blood glucose, poor glycemic control, creatinine, and Hs-CRP were all associated with different dyslipidemia patterns in multivariate logistic regression analyses., Conclusions: We found that the prevalence of dyslipidemia, especially atherogenic patterns, was extremely high among Somali T2DM patients. An enhanced health policy should, therefore, be established to detect, treat and prevent dyslipidemia., (© 2022. The Author(s).)

Background: Hypertriglyceridemia is an important feature of dyslipidemia in type 1 and type 2 diabetic patients and associated with the development of atherosclerotic cardiovascular disease. Recently, variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the clinical impact of serum triglyceride variability, and their cumulative exposure estimates on cardiovascular prognosis in diabetic patients., Methods: A total of 25,933 diabetic patients who had serum triglyceride levels measured at least 3 times and did not have underlying malignancy, myocardial infarction (MI), and stroke during the initial 3 years (modeling phase) were selected from three tertiary hospitals. They were divided into a high/low group depending on their coefficient of variation (CV) and cumulative exposure estimate (CEE). Incidence of major adverse event (MAE), a composite of all-cause death, MI, and stroke during the following 5 years were compared between groups by multivariable analysis after propensity score matching., Results: Although there was a slight difference, both the high CV group and the high CEE group had a higher cardiovascular risk profile including male-dominance, smoking, alcohol, dyslipidemia, and chronic kidney disease compared to the low groups. After the propensity score matching, the high CV group showed higher MAE incidence compared to the low CV group (9.1% vs 7.7%, p = 0.01). In contrast, there was no significant difference of MAE incidence between the high CEE group and the low CEE group (8.6% vs 9.1%, p = 0.44). After the multivariable analysis with further adjustment for potential residual confounding factors, the high CV was suggested as an independent risk predictor for MAE (HR 1.19 [95% CI 1.03-1.37])., Conclusion: Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MAE in diabetic patients., (© 2022. The Author(s).)

Background Although the effects of psychological health and optimism have been extensively investigated, data from community-based cohorts assessing the association between psychological health and cardiovascular disease risk factors are sparse, and the concurrent relationship between subjective well-being and cardiovascular health has not been studied. Methods and Results The current cross-sectional study examined the association between well-being and cardiovascular risk factors among 719 individuals living in a middle- to low-income neighborhood. After adjusting for age, sex, race, body mass index, education, smoking status, and exercise status, we found that higher levels of well-being were significantly associated with lower odds of dyslipidemia (odds ratio [OR], 0.7 [95% CI, 0.55-0.85]) and hypertension (OR, 0.8 [95% CI, 0.63-0.92]). Greater well-being was also significantly associated with lower triglyceride levels (mean difference [M diff ], 7.6 [-14.31 to -0.78]), very low-density lipoprotein (M diff , 0.9 [-1.71 to -0.16]), total cholesterol to high-density lipoprotein ratio (M diff , 3.9 [-6.07 to -1.73]), higher high-density lipoprotein levels (M diff , 1.6 [0.46-2.75]), and lower Framingham Risk Scores (M diff , -7.1% [-10.84% to -3.16%]). Well-being also moderated the association between age and arterial stiffness. The strongest association between arterial stiffness and age was found for those with the lowest well-being scores; there was no association between age and arterial stiffness at high levels of well-being. Conclusions In a community-based cohort, individuals reporting higher levels of well-being have lower odds of hypertension and dyslipidemia as well as lower rates of age-dependent increase in vascular stiffness. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03670524.

Abnormalities in the lipid profile are common, but it is often not easy to determine their cause. After exclusion of secondary causes, a primary (genetic) cause of dyslipidaemia should be considered. The most common monogenic dyslipidaemia is familial hypercholesterolemia (FH), but there are other clinically relevant genetic dyslipidaemias, including familial dysbetalipoproteinaemia (FD), monogenic chylomicronaemia and hypoalphalipoproteinemia. It is important to make a genetic diagnosis because it may influence the prognosis of the patient, for determining appropriate treatment goals and because it is relevant for family members. This clinical viewpoint explains the diagnostic process of genetic dyslipidaemias using two cases.

Background: Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda., Methods: In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity., Results: Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4-69.1), hypertension (40.6%; 33.8-47.9), central obesity (39.3%; 32.9-46.1), smoking (36.3%; 30.1-43.1), high BMI (8.0%; 5.0-12.8) and DM (6.5%; 3.7-11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06-1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14-3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21-0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00-1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00-1.06)., Conclusion: There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB., (© 2022. The Author(s).)

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a healthy lifestyle is the first line of therapy for treatment. A healthy dietary pattern is a cornerstone for treating elevated low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG), both of which are hallmarks of dyslipidemia. Much research has been conducted evaluating the effect of different dietary patterns on LDL-C and TG, both eucalorically and with weight loss. Herein we review studies that have evaluated the effects of different dietary patterns on LDL-C and TG. Within the context of a healthy dietary pattern, constituent food and nutrient intakes impact LDL-C and TG lowering. Food- and nutrient-based recommendations for lowering both LDL-C and TG, will also be reviewed. Finally, the suitability of popular diets for patients with dyslipidemia will be discussed. Lifestyle interventions, including dietary intervention, should be individualized and customized to patient preferences to achieve clinically relevant lipid/lipoprotein improvements., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The aim of the study was to analyze the polymorphism of APOE and SLCO1B1 genotype and correlation with blood lipid levels in patients with dyslipidemia in Hunan Province, China., Methods: Concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were retrospectively analyzed from 396 patients with dyslipidemia from 2016 to 2020. The APOE and SLCO1B1 genotypes were detected by PCR-fluorescent probe. SPSS21.0 software was used to analyze the gene frequency and their correlation., Results: The frequency of E3/E3 genotype was the highest in the APOE gene, reaching 64.14%. The concentrations of LDL-C and TC in E4 phenotype group were the highest and were statistically different from those in E2 and E3 phenotype groups (p < 0.05). There were significant differences in E4 phenotype between the dyslipidemia group and the normolipidemia group (p < 0.05). The frequency of *1b/*1b genotype was the highest in the SLCO1B1 gene, reaching 41.41%. The concentrations of TC and LDL-C in the intermediate OA1P1B1 function group were higher than those in the normal OA1P1B1 function group and the differences were statistically significant (p < 0.05)., Conclusions: The genotypes of APOE and SLCO1B1 gene are correlated with concentration of TC and LDL-C, and their genotypes frequency distribution have regional differences.

Cardiovascular diseases (CVD) remain the leading cause of death globally, and further efforts are being undertaken to understand and modify CVD risk factors, such as dyslipidemia (DLD), hypertension, and diabetes. The sedentary lifestyle of most individuals today contributes to the prevalence of these conditions. Uncontrolled dyslipidemia serves as a fertile ground for atherosclerotic plaque formation, while lipoproteins (Lp) act as cofactors for inflammatory processes that cause plaque destabilization leading to subsequent CVD events. As such, many health experts and institutions continue to emphasize the importance of cardiorespiratory fitness (CRF) and muscular strength (MusS) with the intent to reduce atherogenic lipoproteins and proprotein convertase subtilisin kexin type 9 (PCSK-9) expression. Concordantly, the two modes of exercise training (ET), such as aerobic ET (aET) and resistance ET (rET) have both demonstrated to improve CRF and MusS, respectively. Although both modes of ET were shown to independently reduce mortality, participation in both forms resulted in a more pronounced improvement in cholesterol levels and CVD-related mortality. Though reduction of adiposity is not a pre-requisite to achieve better control of DLD through increased CRF and MusS, the beneficial effects of physical activity on the inflammatory processes linked to atherosclerosis are almost always associated with a simultaneous decrease in overall adiposity. It is therefore essential to promote both aET and rET, including weight loss in order to attenuate the risks stemming from atherosclerosis and its proinflammatory components., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The global burden of peripheral arterial disease (PAD) is substantial. Reducing the major modifiable risk factors for noncommunicable disease, including dyslipidaemia, represents a public health priority. Aim is to evaluate the prevalent adequate use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) attainment among patients with PAD of the lower extremities undergoing percutaneous transluminal angioplasty. Patients and methods: We screened PAD patients treated at the University Hospital Zurich (January 2012-December 2018). We excluded patients <18 years, without classifiable severity of PAD, or with missing LDL-C or medication data. In this cross-sectional study, we studied the prevalent LLT use and LDL-C values in target according to the most recent European guidelines. Available clinical data included demographic information, lipid profile, type and dose of LLT, characteristics of the artery obstruction and angioplasty. Results: A total of 2,148 angioplasties were performed in 956 patients: 614 (64%) were men; the mean age was 70.6 (SD 11.4) years. A total of 608 (64%) had a non-critical PAD (Fontaine stage I-IIb), whereas the remaining had a critical limb ischemia or a diabetic foot syndrome. Their median LDL-C value was 2.00 (Q1-Q3: 1.50-2.60) mmol/L. In accordance to the 2016 and 2019 European Society of Cardiology guidelines, the LDL-C target of 1.8 and 1.4 mmol/L was not reached in 63% (n=599) and in 79% (n=760) of patients, respectively. Only 41% (n=390) of patients were on high-intensity statin therapy. Conclusions: The attainment of LDL-C targets, as recommended by current European guidelines, and the use of high-intensity LLT were unsatisfactory in the majority of PAD patients.

Adequate management of lipid disorders during pregnancy is essential given the association of dyslipidemia with adverse pregnancy outcomes. While there are physiologic changes in lipid levels that occur with normal pregnancy, abnormal alterations in lipids can lead to increased future risk of atherosclerotic cardiovascular disease. There are inherent challenges in the treatment of dyslipidemias during pregnancy and the postpartum period given the lack of adequate data in this population and the contraindication of traditional therapeutic agents. However, it remains of utmost importance to optimize screening and identification of patients at high-risk for atherosclerotic cardiovascular disease so that proper counseling can be provided and the risk for pregnancy complications and downstream cardiovascular complications can be addressed. In this review, we summarize the literature on the association of dyslipidemia in pregnancy with adverse outcomes and discuss considerations for the management of lipid disorders during both pregnancy and breastfeeding., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Klotho deficiency is a significant predictor of cardiovascular disease (CVD)-related mortality and morbidity. However, research assessing the association between klotho and individual risk factors of CVD is limited. This study aimed to explore the association between circulating serum klotho levels and risk factors for CVD in adults., Methods: We used the 2007-2016 National Health and Nutrition Examination Survey and included 13,154 participants for whom serum klotho levels were available. Body mass index (BMI), exercise, smoking status, alcohol consumption, hypertension, dyslipidemia, serum lipid parameters, and blood pressure were considered as CVD risk factors., Results: Circulating klotho levels were negatively associated with being overweight (beta coefficient: - 22.609, p = 0.0025), obesity (beta coefficient: - 23.716, p = 0.0011), current smoking (beta coefficient: - 46.412, p < 0.0001), and alcohol consumption (beta coefficient: - 51.194, p < 0.0001). There was a positive association between serum klotho levels and no history of dyslipidemia (beta coefficient: 15.474, p = 0.0053). Serum klotho levels were significantly decreased by a unit increase in triglycerides (beta coefficient: - 0.117, p = 0.0006) and total cholesterol (beta coefficient: - 0.249, p = 0.0002). There was a significant non-linear relationship between serum klotho levels, triglycerides, and total cholesterol., Conclusions: Lower serum klotho levels are associated with certain CVD risk factors, including high BMI, smoking, alcohol consumption, and lipid parameters (triglycerides and total cholesterol). This study suggests that the soluble klotho level may be a potential marker for CVD risk., (© 2022. The Author(s).)

Purpose: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia., Methods: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients., Findings: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups., Implications: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy., Clinicaltrials: gov identifier: NCT04584736., Competing Interests: Declaration of Interest The authors have indicated that they have no conflicts of interest regarding the content of this article. The sponsor supplied the investigational products and funded the laboratory tests and clinical research coordinator expenses. The funding source had no involvement in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: This study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia., Methods: This was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study., Findings: A total of 388 patients were randomly assigned to the 1PC111 (n = 128), pitavastatin (n = 132), or ezetimibe (n = 128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (-50.50% [14.9%]) compared with either the pitavastatin (-36.11% [11.4%]; P < 0.001) or ezetimibe (-19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non-HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups., Implications: 1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients., Clinicaltrials: gov identifier: NCT04643093., Competing Interests: Declarations of Interest Dr Jong has received honoraria for lectures from Orient EuroPharma, Novartis, Pfizer, and Merck. Dr Chao has received honoraria for lectures from Orient EuroPharma. The other authors have indicated that they have no conflicts of interest of grants, honoraria, consultancies, speakers bureau or advisory board positions, or significant stock holdings received from industry or organizations, regarding the content of this article. The study sponsor had a role in the study design: the collection, analysis, and interpretation of data. The decision to submit the manuscript for publication was made by the authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: While randomized controlled trials have historically served as the gold standard for shaping guideline recommendations, real-world data are increasingly being used to inform clinical decision-making. We describe ways in which healthcare systems are generating real-world data related to dyslipidemia and how these data are being leveraged to improve patient care., Recent Findings: The electronic medical record has emerged as a major source of clinical data, which alongside claims and pharmacy dispending data is enabling healthcare systems the ability to identify care gaps (underdiagnosis and undertreatment) in patients with dyslipidemia. Availability of this data also allows healthcare systems the ability to test and deliver interventions at the point-of-care. Real-world data possess great potential as a complement to randomized controlled trials. Healthcare systems are uniquely positioned to not only define care gaps and areas of opportunity, but to also to leverage tools (e.g., clinical decision support, case identification) aimed at closing them., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The recommendations of the semFYC's Program for Preventive Activities and Health Promotion (PAPPS) for the prevention of cardiovascular diseases (CVD) are presented. The following sections are included: epidemiological review, where the current morbidity and mortality of CVD in Spain and its evolution as well as the main risk factors are described; cardiovascular (CV) risk and recommendations for the calculation of CV risk; main risk factors such as arterial hypertension, dyslipidemia and diabetes mellitus, describing the method for their diagnosis, therapeutic objectives and recommendations for lifestyle measures and pharmacological treatment; indications for antiplatelet therapy, and recommendations for screening of atrial fibrillation, and recommendations for management of chronic conditions. The quality of testing and the strength of the recommendation are included in the main recommendations., (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth., Methods: One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve., Results: Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05)., Conclusions: The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia., (© 2022. The Author(s).)

Aims: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP)., Methods and Results: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was &lt;140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination., Conclusion: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Werner syndrome is a premature ageing disorder caused by biallelic variants in the WRN gene. WRN encodes a dual DNA helicase/exonuclease enzyme. Molecular diagnosis is commonly only made at a late disease stage in the third or fourth decade, when cardinal features have become apparent. We describe a 28 year-old woman who presented with early onset diabetes associated with partial lipodystrophy, severe dyslipidaemia and rapidly progressive liver fibrosis related to non-alcoholic steatohepatitis in the absence of progeroid features. Werner syndrome was diagnosed by trio exome analysis, which revealed compound heterozygous WRN mutations: the known variant c.1290&#95;1293del (p.Asn430Lysfs*7) and the novel intronic splice site variant c.2732+5G>A. cDNA analysis demonstrated this to lead to in-frame skipping of exon 22, predicted to delete most of the zinc binding region of the helicase domain. We suggest that including the WRN gene in genetic analysis of early onset diabetes, lipodystrophy or dyslipidaemia would allow for the opportunity to diagnose some cases of Werner syndrome long before clinical criteria are met, thereby allowing early implementation of important primary prevention interventions., Competing Interests: Declaration of interest Authors have no conflict of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD is associated with dyslipidemia, and cardiovascular mortality remains the leading cause of death. While statins are the first-line therapy in hyperlipidemia, their utilization has been suboptimal. Hence, we examined the use of statins in NAFLD and mortality., Research Design and Methods: Analysis was performed with the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. Longitudinal outcomes were assessed with survival analysis., Results: Of 12,538 NAFLD patients, 6,452 were indicated for hyperlipidemia treatment. Statin usage was highest among high-risk individuals (44.28%) and lowest among low-risk individuals (8.48%). The risk of overall (HR: 0.87, CI: 0.76 to 0.99, p = 0.04) and cancer-related (SHR: 0.73, CI: 0.54 to 0.99, p = 0.04) mortality was significantly lower in NAFLD patients with statins. There was no significant decrease in cardiovascular-related mortality., Conclusion: Over concerns of hepatotoxicity and lack of evidence in reducing mortality events, statins remain underutilized in NAFLD. However, statin use was associated with a significant reduction in overall and cancer-related mortality. The lack of reduction in cardiovascular disease mortality is likely a selection bias of patients, where individuals with higher risk are more likely to receive treatment.

Research Question: Is there an association between fructose and dislipidaemia in polycystic ovary syndrome (PCOS)?, Design: Serum fructose levels were measured in 250 women with PCOS (113 with dislipidaemia, 137 with normolipidaemia) and 460 controls (70 with dislipidaemia, 390 with normolipidaemia). Logistic regression was used to model the relationship between serum fructose levels and dyslipidaemia. Receiver operating characteristic curve analysis was used to assess the ability of serum fructose levels to predict dislipidaemia in women with PCOS, and PCOS in women with dislipidaemia., Results: Patients with PCOS and dislipidaemia had higher serum fructose levels. Triglycerides, total cholesterol and low-density lipoprotein cholesterol increased with increasing serum fructose quartiles in patients with PCOS, whereas high-density lipoprotein cholesterol decreased (all P < 0.001). Among the lipid metabolism-related indicators, triglycerides were most associated with fructose (R = 0.626, P < 0.001). Serum fructose at a cut-off value of 9.79 pmol/µl had a sensitivity of 83.2% and specificity of 66.4% for predicting dislipidaemia in women with PCOS. Lower serum fructose levels were strongly associated with a decreased risk of dislipidaemia in women with PCOS (P < 0.001; OR 0.067; 95% CI 0.027 to 0.170). Moreover, high fructose levels are predictive of PCOS in women with dislipidaemia, with a better diagnostic performance than the androgens typically used as markers., Conclusion: Serum fructose levels are significantly correlated with dislipidaemia in women with PCOS, highlighting the importance of investigating the role of fructose in lipid metabolism of PCOS., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The prevalence of cardiovascular disease (CVD) is high in China, especially in Northwest China, and dyslipidemia in diabetes is a major factor at risk for CVD. The dyslipidemia prevalence, treatment and control among type 2 diabetes mellitus (T2DM) patients in Northwest China were investigated., Methods: In the cross-sectional retrospective research, 1386 medical records of T2DM patients were collected from the Endocrine Department of Tangdu Hospital. And patients' age, sex, diabetes duration, glycated hemoglobin (HbA1c), complications, lipid levels, and drug use were recorded. The patient characteristics, lipid level and lipid-lowering therapy were analyzed., Results: In this study, the dyslipidemia prevalence among T2DM patients was 87.7%, the treatment rate was 68.0%. The overall control rate of low-density lipoprotein cholesterol (LDL-C) was 43.1%, and control rates reached 52.7% for high-risk subjects and 36.1% for very high-risk subjects. The overall control rate of non-high-density lipoprotein cholesterol (non-HDL-C) was 19.8%. HbA1c (%) ≥ 7 was indicated as a major factor predicting failure of LDL-C and non-HDL-C control [odds ratio (OR) 1.521; 2.206, 95% confidence interval (CI) 1.154-2.005; 1.583-3.076)]., Conclusion: Among patients with T2DM, it is high prevalence of dyslipidemia and low rate of treatment and control, and higher HbA1c level is the main factor for poor lipid control. It calls for more efforts to promote early screening, prevention and treatment of dyslipidemia for patients, thereby reducing the risk of CVD., (© 2022. The Author(s).)

Background: The current study aimed to examine the association between drinking water quality and cognitive function and to identify the direct and indirect effects of drinking water quality and dyslipidemia on cognitive function among older adults in China., Methods: Primary data for the study were selected from China Health and Retirement Longitudinal Study (CHARLS, 2015) and 4,951 respondents aged 60 and above were included. Data on drinking water quality were selected from the 2015 prefectural water quality data from the Institute of Public and Environment Affairs in China and measured by the Blue City Water Quality Index. Dyslipidemia was measured by self-reported dyslipidemia diagnosis and lipid panel. Three composite measures of cognitive function included mental status, episodic memory, and global cognition. Mixed effects models were conducted to assess the associations between drinking water quality or dyslipidemia and cognitive function. The mediation effects of dyslipidemia were examined by path analyses., Results: Exposure to high quality drinking water was significantly associated with higher scores in mental status, episodic memory, and global cognition (β = 0.34, p < 0.001 for mental status; β = 0.24, p < 0.05 for episodic memory; β = 0.58, p < 0.01 for global cognition). Respondents who reported dyslipidemia diagnosis had higher scores in the three composite measures of cognitive function (β = 0.39, p < 0.001 for mental status; β = 0.27 p < 0.05 for episodic memory; β = 0.66, p < 0.001 for global cognition). An elevated blood triglycerides was only associated with higher scores in mental status (β = 0.21, p < 0.05). Self-reported dyslipidemia diagnosis was a suppressor, which increased the magnitude of the direct effect of drinking water quality on mental status, episodic memory, and global cognition., Conclusion: Drinking water quality was associated with cognitive function in older Chinese and the relationship was independent of natural or socioeconomic variations in neighborhood environments. Improving drinking water quality could be a potential public health effort to delay the onset of cognitive impairment and prevent the dementia pandemic in older people., (© 2022. The Author(s).)

Background and Aims: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC)., Methods and Results: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose., Conclusions: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

There is limited guidance on laboratory reporting and interpretation of lipids and lipoproteins used in cardiovascular risk stratification. This contributes to inconsistencies in lipid reporting across clinical laboratories. Recently, the Canadian Cardiovascular Society (CCS) published the 2021 CCS guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. A subcommittee of the Working Group on Reference Interval Harmonization of the Canadian Society of Clinical Chemists has developed harmonized lipid reporting recommendations that are aligned with the 2021 CCS guidelines, to improve the standardization of lipid assessment and clinical decision-making. The proposed harmonized lipid reporting recommendations were critically reviewed by a broad range of laboratory and clinical experts across Canada. Feedback from approximately 30 expert reviewers was reviewed by the Working Group on Reference Interval Harmonization lipid subcommittee, and consensus decisions were incorporated into the 2021 harmonized lipid reporting recommendations. In this position statement, we provide 6 recommendations for laboratory reporting of lipid parameters. These recommendations include implementing the new National Institutes of Health equation to replace the Friedewald equation for calculating low-density lipoprotein cholesterol, offering lipoprotein (a), either as an in-house or send-out test, and using assays that report lipoprotein (a) in molar units (nmol/L). We also developed a harmonized lipid reporting format with interpretive comments that includes flagging results based on screening patients using treatment decision thresholds in a primary prevention setting. Overall, harmonized lipid reporting will help bridge the gap between clinical guideline recommendations and clinical laboratory reporting and interpretation, and will improve cardiovascular risk assessment across Canada., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents-especially antisense RNA and monoclonal antibodies-targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Adiponectin is a recognized antiatherogenic molecule; this study was aimed at clarifying the effects of adiponectin variants on lipid and adiponectin levels., Methods: By searching PubMed and Cochrane databases for studies published before March 31, 2022, a total of 86,610 individuals were included in the analysis., Results: Variants of rs2241766 and rs266729 were associated with decreased adiponectin and high-density lipoprotein cholesterol (HDL-C), as well as increased triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the rs1501299 variant was correlated with increased adiponectin and HDL-C, as well as decreased TG, TC, and LDL-C levels. Subgroup analysis indicated that the significant effect of the rs2241766 and rs266729 variants on lipid profile was predominant in Chinese, while the significant effect of the rs1501299 variant on lipid profile was primarily in Caucasians. Moreover, a stronger effect of the rs2241766 and rs1501299 variants on LDL-C levels was observed in males, while a considerable effect of the rs266729 variant on LDL-C levels was observed in children., Conclusions: The present study indicated that Chinese with the rs2241766 and rs266729 variants were at high risk of dyslipidemia, atherosclerosis, or coronary artery disease (CAD). Males with the rs2241766 variant were at high risk of CAD. Children with the rs266729 variant had a high risk to develop dyslipidemia, atherosclerosis, and even early onset of CAD in the future. These findings are beneficial to clinical physicians to choose different management strategies for cardiovascular disease (CVD) prevention., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Guiqing Wang et al.)

Learning Objectives: At the end of the activity, participants will be able to:Summarize important findings and trends involving women and atherosclerotic cardiovascular disease (ASCVD). Characterize the multiple cardiometabolic changes that occur during menopause and the associated ASCVD risk. Discuss the challenges of assessing ASCVD risk and dyslipidemia management in women. Identify women with elevated ASCVD risk and implement guideline-recommended statin therapy.

Introduction and Objectives: Clinical guidelines recommend specific drugs for type 2 diabetes (T2D), hypertension, and dyslipidemia in patients with non-alcoholic fatty liver disease (NAFLD) and/or non-alcoholic steatohepatitis (NASH). We aimed to investigate the differences in prescription trends of antidiabetic, antihypertensive, and lipid-lowering drugs among adult patients according to the presence of comorbid NAFLD and/or NASH., Methods: We conducted a cross-sectional analysis using a large claims database from January 2013 to December 2020., Results: Among 7,716,908 people, 47,157 patients with T2D, 180,050 with hypertension, and 191,348 with dyslipidemia were identified. A total of 8,897, 16,451, and 24,762 patients with NAFLD, as well as 435, 523, and 1033 patients with NASH, had T2D, hypertension, and dyslipidemia, respectively. Among antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2is) and thiazolidine were more frequently prescribed to patients with NAFLD than to those without NAFLD (non-NAFLD) (thiazolidine: 1.4% and 2.8% and SGLT2is: 17.8% and 25.9% for non-NAFLD and NAFLD, respectively [2019-2020]). Among antihypertensive drugs, angiotensin II receptor antagonists exhibited a slightly higher prescription ratio in patients with NAFLD (33.6% vs. 39.0%). Regarding lipid-lowering drugs, fibrates were more frequently prescribed to patients with NAFLD (10.3% vs. 18.4%)., Conclusions: Specific drugs tended to be prescribed to patients with NAFLD. However, the differences in prescription ratios were not considerable. Further investigation is required to confirm the effects of drugs on the prognosis of patients with NAFLD or NASH., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Findings of prior investigations on the association between calcium intake and lipid profiles were inconsistent. We performed a systematic review and meta-analysis on epidemiologic studies to evaluate the relationship of dietary calcium intake with blood lipids and lipoproteins., Data Synthesis: A systematic search up to April 2021 was performed in different electronic databases, including MEDLINE (PubMed), Scopus, Web of Science (ISI), and Google Scholar for epidemiological studies that considered dietary calcium intake as the exposure and reported risk of dyslipidemia or blood lipids and lipoproteins concentrations (as mean ± SD or mean ± SE or median (Inter Quartile Range) as the outcomes of interest in adult populations from both genders (18 years or older), regardless of their health status. Nineteen cross-sectional studies were included in the analysis. Combining estimates from 11 studies (including 33,304 subjects) revealed that individuals in the highest category of calcium intake, compared to the lowest one, had 5.94 mg/dL lower circulating triglyceride (TG) concentration (weighted mean difference (WMD): -5.94; 95% CI: -8.27, -3.62), 4.02 mg/dL lower circulating low-density lipoprotein cholesterol (LDL-c) levels (WMD: -4.02; 95% CI: -7.08, -0.95), and 1.56 mg/dL higher blood high-density lipoprotein cholesterol (HDL-c) (WMD: 1.56; 95% CI: 0.81, 2.30). Although meta-analysis on 13 studies (including 38,714 participants) did not reveal a significant relationship between dietary calcium intake and odds of dyslipidemia or hyperlipidemia in the whole population, the highest vs. lowest level of calcium intake was related to 42% decreased odds of low blood HDL-c levels in females (95% CI: 0.40, 0.84) and 41% increased odds in males (95% CI: 1.21, 1.65)., Conclusions: This meta-analysis demonstrated that individuals with the highest dietary calcium intake might have lower blood TG, LDL-c, and higher HDL-c concentrations as compared to those with the lowest calcium intake. However, the linkage between dietary calcium intake with odds of hyperlipidemia or dyslipidemia was not significant. Because of the cross-sectional nature of included studies, causality could not be proven. Further prospective studies are needed to affirm these findings., Competing Interests: Declaration of competing interest The authors declared no personal or financial conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients., Methods and Results: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04)., Conclusion: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest in connection with submitted material., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: Thyroid cancer (TC) prevalence has been rapidly increasing. While the relationship between thyroid hormones and lipids has been widely investigated, studies regarding dyslipidemia in patients with TC have been scarce and controversial. We aimed to investigate dyslipidemia risk after TC diagnosis compared to the general population without TC., Method: A population-based prospective study was conducted using data from the Korean National Health Insurance Service-National Sample Cohort Database 2.0 (NHIS-NSC DB 2.0), with health insurance claim data of 1,108,369 subjects between 2002 and 2015. The final study sample comprised 466,735 adult subjects without TC or dyslipidemia diagnoses before the index year, 2009. Bidirectional analyses were performed using prospective and retrospective concepts. In the prospective analysis, Kaplan-Meier estimates were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between TC and dyslipidemia. The retrospective analysis involved 1:5 nested case-control matching based on dyslipidemia status and conditional logistic regression analysis., Results: No significant difference in dyslipidemia incidence was observed between TC patients and the control group, in either the prospective matched (log-rank P = 0.483) or non-matched (log-rank P = 0.424) analyses, or the retrospective analysis (P = 0.3724). In the prospective analysis, 193 patients after TC diagnosis showed similar risk of developing dyslipidemia with the 466,542 controls during the median 7 years of follow-up (unadjusted hazard ratio [HR], 1.102; 95% confidence interval [CI], 0.878-1.383; adjusted HR, 0.932; 95% CI, 0.707-1.230). Multiple propensity score-adjusted models showed similar results, and 114 patients and 570 matched controls showed an HR of 0.818 (95% CI, 0.598-1.120). In the retrospective comparison of dyslipidemia risk in 170 patients and 277,864 controls, the odds ratio was 0.822 (95% CI, 0.534-1.266)., Conclusions: Dyslipidemia risk was not significantly different between patients with TC and the general population, in both prospective and retrospective analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Lee, Park, Kang and Lee.)

Background There are few studies on the association with Kawasaki disease in children and the family's history of cardiovascular disease (CVD). The aim of this study was to identify the association of increased risks for Kawasaki disease in children with a family history of CVD. Methods and Results Clinical data of children born in 2008 and 2009 (n=917 707) were obtained from the National Health Insurance Service and the National Health Screening Program for Infants and Children for this study. The cohort consisted of 495 215 participants (53.8%) who completed the family history questionnaire for children 54 to 60 months old. Family history of CVD included 5 medical conditions: hypertension, dyslipidemia, myocardial infarction, stroke, and diabetes. Kawasaki disease was defined using the disease code, intravenous immunoglobulin prescription, and use of antipyretics for more than 25 days. Severe Kawasaki disease was defined as diagnosis of accompanied cardiac/coronary artery complications or intravenous immunoglobulin use ≥2 times. The incidence rate of Kawasaki disease was 124/100 000 person-years (95% CI, 117.5-131.5) for children <2 years old, 95/100 000 person-years (95% CI, 90.5-100.4) in children 2 to 5 years old, and 14/100 000 person-years (95% CI, 12.6-15.6) in children >5 years old. After propensity-score matching, 829 participants with a family history of CVD were diagnosed as having Kawasaki disease (0.68% [95% CI, 0.63-0.72]), and 690 patients with Kawasaki disease (0.56% [95% CI, 0.52-0.61]) had no family history of CVD. The family history of CVD was associated with increased risk for Kawasaki disease (risk ratio, 1.20 [95% CI, 1.08-1.32]) but not for severe Kawasaki disease (risk ratio, 1.23 [95% CI, 0.92-1.65]). Conclusions In this nationwide propensity-score matched study, those with a family history of CVD had a significantly greater risk of Kawasaki disease compared with those who had no family history of CVD.

Background Determine the prevalence and predictors associated with underdiagnosis and undertreatment of modifiable cardiovascular disease (CVD) risk factors (hypertension, dyslipidemia, glucose intolerance/diabetes) among adult survivors of childhood cancer at high risk of premature CVD. Methods and Results This was a cross-sectional study of adult-aged survivors of childhood cancer treated with anthracyclines or chest radiotherapy, recruited across 9 US metropolitan regions. Survivors completed questionnaires and in-home clinical assessments. The comparator group was a matched sample from the National Health and Nutrition Examination Survey. Multivariable logistic regression estimated the risk (odds ratios) of CVD risk factor underdiagnosis and undertreatment among survivors compared with the National Health and Nutrition Examination Survey. Survivors (n=571; median age, 37.7 years and 28.5 years from cancer diagnosis) were more likely to have a preexisting CVD risk factor than the National Health and Nutrition Examination Survey (n=345; P <0.05 for all factors). While rates of CVD risk factor underdiagnosis were similar (27.1% survivors versus 26.1% National Health and Nutrition Examination Survey; P =0.73), survivors were more likely undertreated (21.0% versus 13.9%, P =0.007; odds ratio, 1.8, 95% CI, 1.2-2.7). Among survivors, the most underdiagnosed and undertreated risk factors were hypertension (18.9%) and dyslipidemia (16.3%), respectively. Men and survivors who were overweight/obese were more likely to be underdiagnosed and undertreated. Those with multiple adverse lifestyle factors were also more likely undertreated (odds ratio, 2.2, 95% CI, 1.1-4.5). Greater health-related self-efficacy was associated with reduced undertreatment (odds ratio, 0.5; 95% CI, 0.3-0.8). Conclusions Greater awareness of among primary care providers and cardiologists, combined with improving self-efficacy among survivors, may mitigate the risk of underdiagnosed and undertreated CVD risk factors among adult-aged survivors of childhood cancer. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03104543.

Background and Aims: The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort., Methods: We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up., Results: The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (< 0.02 kg/m 2 ) to 1.17 in the second (0.02-1.29), and 1.46 in the highest tertile (> 1.29) (p for interaction < 0.001). Associations of each 1-unit of BMI (kg/m 2 ) increase with incident dyslipidemia were more prominent in the AA carriers (OR = 1.50, 95%CI [1.26-1.80], p < 0.001), while much weaker in the GA (OR = 1.10) or GG carriers (OR = 1.09) (p for interaction  = 0.002). Similar results were found for the risk of incident higher triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL-c), or the longitudinal changes in log 10 -TG (all p for interaction ≤ 0.02)., Conclusions: BMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Non-communicable diseases like systemic arterial hypertension (SAH) and dyslipidemia are poorly studied in terms of patient journey aspects. This semi-systematic review provides evidence synthesis for the management of SAH and dyslipidemia in Brazil and also discusses challenges faced by patients at the local level along with a suggested care approach by local experts., Methods: A semi-systematic review using both structured literature databases (Embase and Medline) and unstructured scientific records (WHO, IPD, MOH and Google) on hypertension and dyslipidemia in the English language from 2010 to 2019 was performed by reviewers. After two-level screening based on pre-defined criteria, patient journey touchpoints and prevalence information were extracted from the included articles. Data gaps were bridged through the insights of local experts., Results: Prevalence of hypertension and dyslipidemia in Brazil were 23% and 40.8%, respectively. Awareness of dyslipidemia was found in a larger proportion (58.1%) than in SAH (22.2%). Similarly, screening for hypertension (97%) and dyslipidemia (55.4%) were found to be effective, while treatment was (62.9%) and (30.0%) for hypertension and dyslipidemia, respectively., Conclusion: There were important gaps on patient awareness and treatment of dyslipidemia and hypertension. Limited patient education, regional disease distribution, and treatment allocation, along with limited resources for diagnosis and treatment are the key challenges., (© 2022. The Author(s).)

Background: Undertreated risk factors are major contributors to the burden of cardiovascular disease (CVD). Those with arthritis have an increased prevalence of CVD risk factors. CVD risk factors are often asymptomatic, which may be a barrier their treatment. Arthritis causes pain and immobility, and is a common reason for individuals to seek healthcare. Our aims were to (1) examine the relationship between arthritis and CVD risk factors in Australian adults, and (2) calculate the proportion of CVD risk factors that could be reduced if individuals with arthritis were targeted., Methods: This cross-sectional study uses data from the 2017-18 Australian National Health Survey which included 13,776 participants, categorised into young (18-39 years), middle aged (40-64 years) and older (≥ 65 years) adults. Hypertension, height and weight were measured. Arthritis, dyslipidemia and diabetes were self-reported. The associations between arthritis and CVD risk factors were examined using logistic regression, and the population attributable fraction (PAF) of arthritis for each CVD risk factor was calculated., Results: Arthritis was reported by 4.0% of young adults, 28.8% of middle-aged adults and 54.5% of older adults. Those with arthritis were at increased odds of obesity (2.07 fold in young, 1.75 fold in middle-aged and 1.89 fold in older adults), increased odds of diabetes (5.70 fold in young, 1.64 fold in middle-aged and 1.37 fold in older adults), increased odds of hypertension (2.72 fold in young, 1.78 fold in middle-aged and 1.48 fold in older adults) and an increased odds of dyslipidaemia (4.64 fold in young, 2.14 fold in middle-aged and 1.22 fold in older adults) compared to those without arthritis. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. This elevated chance remained significant even after adjusting for obesity, with the exception of diabetes in the older population. The PAF of the presence of arthritis for having at least one CVD risk factor was 30.7% in middle-aged adults and 70.4% in older adults., Conclusion: Australian adults of all ages with arthritis are at increased odds of having CVD risk factors. For young and middle-aged adults, this increased odds remains significant even when adjusted for obesity. Presentation to healthcare practitioners with arthritis is an opportunity to screen for asymptomatic CVD risk factors with the potential of improving outcomes for both diseases. By adopting an approach of managing arthritis and CVD risk factors in parallel, rather than in silos, we could reduce the burden of CVD risk factors by 20-30%., (© 2022. The Author(s).)

Background and Aims: There is increasing evidence that lifestyle factors play an important role in the development of hypertension and dyslipidemia. However, existing research usually evaluated these risk factors individually (such as physical activity, smoking, drinking, obesity and so on), rather than joint evaluation. The aim of this study was to quantify the association between a combination of a healthy lifestyle and the risk of hypertension and dyslipidemia., Methods and Result: A healthy lifestyle score was created based on 4 factors: never smoking, moderate to high-intensive physical activity, no alcohol drinking, and normal body mass index. We calculated the healthy lifestyle score using the cumulative number of health factors for each individual. Also, a multivariate analysis was used to assess the relationship between healthy lifestyle and hypertension and dyslipidemia. Among 6446 participants, 650 (10.08%) had lowest healthy lifestyle score (0) and 627 (9.72%) had highest healthy lifestyle score (4), respectively. The adjustment model indicated that participants with the highest score (score: 4), which integrated the four lifestyles, had significantly lower ORs for hypertension compared with the lowest score (score: 0) (0.21; (95%CI: 0.10, 0.43 P-trend< 0.001)). In the adjustment models, compared with lowest healthy lifestyle score, the ORs of highest healthy lifestyle score was: 0.17; (95%CI: 0.07, 0.42 P-trend<0.001) for dyslipidemia., Conclusion: Hypertension and dyslipidemia were negatively correlated with healthy lifestyle score. Interventions with healthy lifestyle to reduce hypertension, dyslipidemia and promote population health are warranted., Competing Interests: Declaration of competing interest No conflicts were reported., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Treating blood pressure (BP) alone may provide only limited benefits while it is recommendable to manage the total cardiovascular risk. To date, several studies have shown that concomitant treatment of hypertension and dyslipidemia with non-pharmacological approaches and/or metabolically neutral antihypertensive drugs and statins produce a significantly greater reduction of the risk of developing cardiovascular disease. Thus, in this review article, we summarize the available evidence regarding non-pharmacological and pharmacological approaches with a favourable effect on both BP and lipids., (© 2022. The Author(s).)

Purpose: LDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C-lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician., Methods: This multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching., Findings: A fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up., Implications: In a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mildly elevated bilirubin, a by-product of hemoglobin breakdown, might mitigate cardiometabolic risk factors including adiposity, dyslipidemia, and high blood pressure (BP). We investigated the cross-sectional relationship between (total) bilirubin and baseline cardiometabolic risk factors in 467,519 UK Biobank study participants., Methods: We used multivariable-adjusted linear regression to estimate associations between bilirubin levels and risk factors of cardiometabolic diseases including body mass index (BMI), waist and hip circumferences (WC, HC), waist-to-hip ratio (WHR), fat mass (FM), and trunk FM, and the blood lipids: apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apoB/apoA-I, lipoprotein (a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL/HDL, TC/HDL, triglycerides (TG). Log-transformed bilirubin was modelled with restricted cubic splines and predicted mean values with 99% confidence intervals (CI) for each risk marker were estimated, separately. Second, we applied principal component analysis (PCA) for dimension reduction to in turn six anthropometric traits (height, weight, BMI, WC, HC, and WHR) and all above lipids. Last, we estimated associations (99%CI) between bilirubin and three components of the metabolic syndrome, i.e. WC, TG, and BP using logistic regression., Results: After multivariable adjustments, higher levels of bilirubin were inversely associated with indicators of general adiposity (BMI and FM) and of body fat distribution (WC, HC, WHR, and trunk FM) in both men and women. For example, women with mildly elevated bilirubin (95 th percentile equal to 15.0 µmol/L), compared to women with low bilirubin (5 th percentile equal to 4.5 µmol/L), had on average a 2.0 kg/m 2 (99% CI 1.9-2.1) lower BMI. Inverse associations were also observed with dyslipidemia among men and women. For example, mildly elevated bilirubin among men (95 th percentile equal to 19.4 µmol/L) compared to low levels of bilirubin (5 th percentile equal to 5.5 µmol/L) were associated with approx. 0.55 mmol/L (99% CI 0.53-0.56) lower TG levels, with similar inverse associations among women. Multiple-trait analyses using PCA confirmed single-trait analyses. Men and women with mildly elevated bilirubin levels ≥ 17.1 µmol/L, compared to low-normal bilirubin < 10 µmol/L had 13% (99% CI 8%-18%) and 11% (99% CI 4%-17%) lower odds of exceeding systolic BP levels of ≥ 130 mm Hg, respectively., Conclusions: Higher levels of bilirubin were inversely associated with cardiometabolic risk factors including adiposity, dyslipidemia, and hypertension., (© 2022. The Author(s).)

Purpose: Women are increasingly concerned by coronary heart disease (CHD), with peculiarities of their own, particularly concerning risk factors. The aim of the study was to assess the risk factors for CHD in Lebanese women over forty., Patients and Methods: A case-control study was carried out in 6 hospitals in Beirut and Mount-Lebanon, from December 2018 to December 2019 including 1500 patients (1200 controls and 300 cases). Women were stratified into pre- and post-menopausal groups. Personal and medical data were collected from hospital records and during an interview where validated questionnaires were used. Binary logistic regressions were performed to investigate potential predictors of CHD in the 2 groups., Results: In post-menopausal women, dyslipidemia (adjusted odds ratio [aOR], 3.018; 95% confidence interval, 2.102-4.332), hypertension (aOR: 2.449, [1.386-4.327]), a family history of CHD (aOR: 2.724, [1.949-3.808]), cigarette smoking (aOR: 2.317, [1.574-3.410]) and common non-rheumatic joint pain (aOR: 1.457, [1.053-2.016]) were strongly associated with CHD. Conversely, living in Mount Lebanon seemed protective, compared to Beirut (aOR: 0.589, [0.406-0.854]), as well as having a moderate monthly income (aOR: 0.450, [0.220-0.923]), adhering to a Mediterranean diet (aOR: 0.965, [0.936-0.994]), and practicing physical activity [PA] (aOR: 0.396, [0.206-0.759] and 0.725, [0.529-0.992], respectively for high and moderate vs low PA). In pre-menopausal women, dyslipidemia (aOR: 6.938, [1.835-26.224]), hypertension (aOR: 6.195, [1.318-29.119]), family histories of dyslipidemia (aOR: 6.143, [1.560-24.191]) and CHD (aOR: 4.739, [1.336-16.805]) reached statistical significance., Conclusion: The identification of factors associated with CHD in women, some of which are frequent and trivialized in post-menopause, underlines the need to put in place specific and dedicated CHD prevention strategies in women., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2022 Ghaddar et al.)

Purpose of Review: To review current progress in the use of polygenic risk scores for lipid traits and their use in the diagnosis and treatment of lipid disorders., Recent Findings: Inherited lipid disorders, including those causing extremes of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides were initially identified as monogenic traits, in which a single rare variant with large effect size is responsible for the phenotype. More recently, a polygenic basis for many lipid traits has also been identified. Patients with polygenic dyslipidemia can be identified through the use of polygenic risk scores (PRSs), which collapse information from a handful to several million genetic variants into a single metric., Summary: PRSs for lipid traits may aid in the identification of the genetic basis for the lipid phenotype in individual patients, may provide additional information regarding the risk of cardiovascular disease, and could help in guiding therapeutic decision making., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Low-density lipoprotein (LDL) cholesterol reduction by statin therapy is dose-dependent, varies among different statins, and has wide inter-individual variability. The present study aimed to compare mean LDL cholesterol reduction and its variability achieved with different doses of the three statins most frequently used in monotherapy or combined with ezetimibe in a real clinical setting., Methods: Of 5620 cases with primary hypercholesterolemia on the Spanish Arteriosclerosis Society Registry, 1004 with non-familial hypercholesterolemia and complete information on drug therapy and lipid profile were included., Results: The lowest mean percentage LDL cholesterol reduction was observed with simvastatin 10 mg (32.5 ± 18.5%), while the highest mean percentage LDL reduction was obtained with rosuvastatin 40 mg (58.7 ± 18.8%). As to combined treatment, the lowest and highest mean percentage LDL cholesterol reductions were obtained with simvastatin 10 mg combined with ezetimibe (50.6 ± 24.6%) and rosuvastatin 40 mg combined with ezetimibe (71.6 ± 11.1%), respectively. Factors associated with a suboptimal response were male sex, lower age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol reduction (OR 0.603, p < 0.001)., Conclusion: In a real clinical setting, rosuvastatin was superior to the other statins in lowering LDL cholesterol, both as monotherapy or combined with ezetimibe. Factors associated with a suboptimal response in LDL cholesterol decline were male sex, age, body mass index, and baseline LDL cholesterol levels. Combined treatment was associated with less variability in LDL cholesterol improvement., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)