Repositioning of the global epicentre of non-optimal cholesterol.

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular risk-changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study.

BACKGROUND: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. METHODS: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. FINDINGS: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. INTERPRETATION: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. FUNDING: Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.

Hypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Hypercholesterolemia is frequently diagnosed in patients with primary biliary cholangitis (PBC). However, its association with the prognosis and lipid metabolism is unknown. In this study, we aimed to investigate the prognostic value of baseline total cholesterol (TC) levels in PBC and characterized the associated lipid metabolism. METHODS: Five hundred and thirty-one patients with PBC without prior cirrhosis-related complications were randomly divided into the derivation and validation cohorts at a ratio of 7:3. Complete clinical data were obtained and analyzed. The endpoints were defined as liver-related death, liver transplantation, and cirrhosis-related complications. Lipidomics was performed in 89 patients and 28 healthy controls. RESULTS: Baseline TC was independently associated with poor liver-related outcomes, and adjusted C-statistics were 0.80 (95% confidence interval [CI]: 0.74-0.85) and 0.88 (95% CI: 0.78-0.91) in the derivation and validation cohorts, respectively. The predictive ability of TC for disease outcomes was stable over time and comparable with the Globe score. The 200 mg/dL cut-off optimally divided patients into low- and high-TC groups. A combination of TC and Globe score provided a more accurate stratification of patients into risk subgroups. Lipidomics indicated an up-regulation of lipid families in high-TC patients. Pathway analysis of 66 up-regulated lipids revealed the dysregulation of glycerophospholipid and sphingolipid metabolism in high-TC patients, which were associated with poor liver-related outcomes. CONCLUSIONS: Our results indicate that patients with PBC having baseline TC levels above 200 mg/dL have unique lipidome characteristics and are at a higher risk of poor liver-related outcomes.

Hypercholesterolemia and the Increased Risk of Vascular Dementia: a Cholesterol Perspective.

PURPOSE OF REVIEW: Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease.Hypercholesterolemia may increase the risk of dementia, but the association between cholesterol and cognitive function is very complex. From the perspective of peripheral and brain cholesterol, we review the relationship between hypercholesterolemia and increased risk of VaD and how the use of lipid-lowering therapies affects cognition. RECENT FINDINGS: Epidemiologic studies show since 1980, non-HDL-C levels of individuals has increased rapidly in Asian countries.The study has suggested that vascular risk factors increase the risk of VaD, such as disordered lipid metabolism. Dyslipidemia has been found to interact with chronic cerebral hypoperfusion to promote inflammation resulting in cognitive dysfunction in the brain.Hypercholesterolemia may be a risk factor for VaD. Inflammation could potentially serve as a link between hypercholesterolemia and VaD. Additionally, the potential impact of lipid-lowering therapy on cognitive function is also worth considering. Finding strategies to prevent and treat VaD is critical given the aging of the population to lessen the load on society. Currently, controlling underlying vascular risk factors is considered one of the most effective methods of preventing VaD. Understanding the relationship between abnormal cholesterol levels and VaD, as well as discovering potential serum biomarkers, is important for the early prevention and treatment of VaD.

Cardiovascular Risk Estimation and Stratification Among Individuals with Hypercholesterolemia.

PURPOSE OF THE REVIEW: This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored. RECENT FINDINGS: The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia.

Subtyping Severe Hypercholesterolemia by Genetic Determinant to Stratify Risk of Coronary Artery Disease.

BACKGROUND: Severe hypercholesterolemia, defined as LDL (low-density lipoprotein) cholesterol (LDL-C) measurement ≥190 mg/dL, is associated with increased risk for coronary artery disease (CAD). Causes of severe hypercholesterolemia include monogenic familial hypercholesterolemia, polygenic hypercholesterolemia, elevated lipoprotein(a) [Lp(a)] hypercholesteremia, polygenic hypercholesterolemia with elevated Lp(a) (two-hit), or nongenetic hypercholesterolemia. The added value of using a genetics approach to stratifying risk of incident CAD among those with severe hypercholesterolemia versus using LDL-C levels alone for risk stratification is not known. METHODS: To determine whether risk stratification by genetic cause provided better 10-year incident CAD risk stratification than LDL-C level, a retrospective cohort study comparing incident CAD risk among severe hypercholesterolemia subtypes (genetic and nongenetic causes) was performed among 130 091 UK Biobank participants. Analyses were limited to unrelated, White British or Irish participants with available exome sequencing data. Participants with cardiovascular disease at baseline were excluded from analyses of incident CAD. RESULTS: Of 130 091 individuals, 68 416 (52.6%) were women, and the mean (SD) age was 56.7 (8.0) years. Of the cohort, 9.0% met severe hypercholesterolemia criteria. Participants with LDL-C between 210 and 229 mg/dL and LDL-C ≥230 mg/dL showed modest increases in incident CAD risk relative to those with LDL-C between 190 and 209 mg/dL (210-229 mg/dL: hazard ratio [HR], 1.3 [95% CI, 1.1-1.7]; ≥230 mg/dL: HR, 1.3 [95% CI, 1.0-1.7]). In contrast, when risk was stratified by genetic subtype, monogenic familial hypercholesterolemia, elevated Lp(a), and two-hit hypercholesterolemia subtypes had increased rates of incident CAD relative to the nongenetic hypercholesterolemia subtype (monogenic familial hypercholesterolemia: HR, 2.3 [95% CI, 1.4-4.0]; elevated Lp(a): HR, 1.5 [95% CI, 1.2-2.0]; two-hit: HR, 1.9 [95% CI, 1.4-2.6]), while polygenic hypercholesterolemia did not. CONCLUSIONS: Genetics-based subtyping for monogenic familial hypercholesterolemia and Lp(a) in those with severe hypercholesterolemia provided better stratification of 10-year incident CAD risk than LDL-C-based stratification.

Hypertriglyceridemia, Hypercholesterolemia, Body Mass Index, and the Risk of Acute Pancreatitis.

OBJECTIVE: The purpose of this work was to check the connection between parameters of lipid profile and body mass index (BMI) in relation to the occurrence of acute pancreatitis within a sample of adults from northern China. METHODOLOGY: A total of 123,214 participants from the Kailuan Group were incorporated into this prospective study. The subjects were categorized into quartiles on the basis of their initial levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). On the basis of BMI classification, the individuals in the study were divided into three distinct groups: normal weight, overweight, and obese. The data were analyzed to explore the correlation between lipid profile and BMI with acute pancreatitis. RESULTS: Over a period of 12.59 ± 0.98 years, during the median follow-up duration, a total of 410 new patients with acute pancreatitis were recorded. The occurrence rate and total occurrence of acute pancreatitis demonstrated an upward trend in correlation with elevated levels of TG, TC, and BMI. Following adjustment for multiple variables, it was observed that individuals in the fourth quartile of TG and TC levels demonstrated the highest likelihood of developing acute pancreatitis. Furthermore, our analysis revealed that a proportion of 19.29% of the correlation between BMI and the likelihood of experiencing acute pancreatitis can be attributed to the influence of elevated TG levels, whereas 12.69% of the association was mediated by higher TC. CONCLUSIONS: We found that hypertriglyceridemia, hypercholesterolemia, and obesity were risk factors for acute pancreatitis, especially in young and middle-aged men.TG and TC were the mediating factors between BMI and the risk of acute pancreatitis.

Dietary cholesterol intake is not associated with the development of chronic kidney disease: Results from two Korean cohort studies.

BACKGROUND AND AIMS: Although dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between cholesterol intake and CKD risk. METHODS AND RESULTS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2019-2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio [HR] per 10 mg increase, 1.00; 95 % confidence interval [CI], 0.99-1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98-1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD. CONCLUSION: Although cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.

Estimating the effect of inclisiran on hypercholesterolemia and primary prevention of cardiovascular disease: the NHANES 1999-2018 study.

BACKGROUND: Hypercholesterolemia has been identified as an independent predictor of cardiovascular disease (CVD). Inclisiran, an innovative small interfering RNA agent, is anticipated to result in a notable reduction of approximately 50% in low-density lipoprotein cholesterol (LDL-C) levels. Given its transformative impact, this study scrutinized the eligibility of the US population for inclisiran treatment and evaluated its potential effects on hypercholesterolemia and the primary prevention of CVD. METHODS: This study applied the eligibility criteria from the ORION 10 and 11 trials to the 1999-2018 National Health and Nutrition Examination Survey (NHANES) dataset to estimate the size of the eligible population for atherosclerotic cardiovascular disease (ASCVD) and ASCVD-risk equivalents. Utilizing the reduction in LDL-C levels from ORION 10, this study predicted the impact of inclisiran on LDL-C levels among ASCVD patients. Similarly, leveraging the changes in lipid levels from ORION 11, this study predicted inclisiran's effect on the 10-year change in CVD risk and preventable CVD events in the ASCVD-risk equivalents population, employing the Framingham CVD Risk Score. RESULTS: The study identified 579 ASCVD patients (5 million) and 382 ASCVD-risk equivalents (2.66 million) who met the eligibility criteria from ORION 10 and 11. Among the ASCVD population, 3.5 million (70.2%) would achieve a ≥ 50% reduction in LDL-C levels after treatment. Furthermore, 4.6 million (91.3%) would achieve LDL-C levels < 70 mg/dL, and 3.8 million (75%) would achieve LDL-C levels < 55 mg/dL after treatment. For the ASCVD-risk equivalents population, the estimated 10-year CVD risk would decrease from 25.3 to 17.7%, an absolute reduction of 7.6% and a relative reduction of 30% following inclisiran treatment, potentially preventing 202,353 CVD events over a decade, including 138,084 coronary heart disease cases, 37,351 strokes, and 23,894 congestive heart failure cases. CONCLUSIONS: Inclisiran has the potential to substantially reduce the prevalence of hypercholesterolemia and prevent nearly 200,000 CVD events in eligible US adults.

Sleep and nighttime behavior disorders in older adults: associations with hypercholesterolemia and hypertriglyceridemia at baseline, and a predictive analysis of incident cases at 12 months follow-up.

INTRODUCTION: Sleep disorders, particularly insomnia and obstructive sleep apnea, are associated with dyslipidemia in the general population. The study's aim was to explore the association between pathological Cholesterol and Triglyceride levels, and sleep and nighttime behavior disorders (SNBD) in older adults, whether they might predict SNBD onset, and to emphasize the role of body mass index (BMI) in this association. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between hypercholesterolemia, hypertriglyceridemia, and SNBD at baseline and at 12 months. Relevant confounders, particularly BMI, were adjusted for. RESULTS: Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 years (IQR: 68, 78). At baseline, 357 (16%) had SNBD and 327 (18%) at 12 months; 187 of them were incident cases. There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, P-value = 0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, P-value = 0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, P-value < 0.001). Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR = 1.43, 95%CI: 1.13,1.80, P-value = 0.003), even after adjustment for confounding factors (adj. OR = 1.36, 95%CI: 1.06,1.74, P-value = 0.016) and (BMI-adj. OR = 1.29, 95%CI: 1.00,1.66, P-value = 0.048). None of the dyslipidemia forms did predict incident cases at 12 months. CONCLUSIONS: Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. The association was independent of BMI. None of the dyslipidemia forms did predict incident SNBD over 12 months. Sleep disorders should motivate a systematic screening of dyslipidemia in older adults and vice versa.

Identifying high cholesterol in the ambulance setting: a mixed-methods cohort study to tackle health inequality.

BACKGROUND: Individuals with low socio-economic status (SES) have disproportionate rates of cardio- vascular disease (CVD) but poorer engagement with preventative health. This study aimed to compare characteristics of individuals with and without hyperlipidaemia and describe their health behaviours. METHODS: A mixed-methods study between January and December 2022. Patients aged ≥40 years using the ambulance service with blood pressure of ≥140/90 had their total cholesterol measured using a point of care device. Data including blood pressure, smoking status, National Early Warning Score 2 and clinical frailty scale (CFS) were analysed. RESULTS: Of 203 patients (59% female, mean age 65.7 years), 115 (56.7%) had total cholesterol ≥5.1 mmol/L. Thirty patients (14.8%) sought treatment and received either statins (n = 9; 4.4%), dietary modification (n = 7; 3.4%) or no further intervention (n = 14; 6.9%), whilst 85 patients (41.9%) took no further action. Lower CFS (OR 0.53 [0.31-0.93]) and higher total cholesterol (OR 2.07 [1.03-2.76]) predicted seeking further management. SES was not associated with hyperlipidaemia or likelihood of seeking further management, rather this was dictated by competing co-morbidity, poor health literacy and digital divide. CONCLUSIONS: Undiagnosed hyperlipidaemia exists in patients using the ambulance service, irrespective of SES. Individual and healthcare system factors prevent engagement in cholesterol lowering behaviours.

Exploring sex variations in the incidence of cardiovascular events: a counterfactual decomposition analysis.

BACKGROUND: Some cardiovascular risk factors (CVRFs) that occur differently in men and women can be addressed to reduce the risk of suffering a major adverse cardiovascular event (MACE). Furthermore, the development of MACE is highly influenced by social determinants of health. Counterfactual decomposition analysis is a new methodology that has the potential to be used to disentangle the role of different factors in health inequalities. This study aimed to assess sex differences in the incidence of MACE and to estimate how much of the difference could be attributed to the prevalence of diabetes, hypertension, hypercholesterolaemia and socioeconomic status (SES). METHODS: Descriptive and counterfactual analyses were conducted in a population of 278 515 people with CVRFs. The contribution of the causal factors was estimated by comparing the observed risk ratio with the causal factor distribution that would have been observed if men had been set to have the same factor distribution as women. The study period was between 2018 and 2021. RESULTS: The most prevalent CVRF was hypercholesterolaemia, which was similar in both sexes, while diabetes was more prevalent in men. The incidence of MACE was higher in men than in women. The main causal mediating factors that contributed to the sex differences were diabetes and SES, the latter with an offsetting effect. CONCLUSIONS: This result suggests that to reduce the MACE gap between sexes, diabetes prevention programmes targeting men and more gender-equal salary policies should be implemented.

Factors associated with prolonged QTc interval in Iranian population: MASHAD cohort study.

AIM: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women. METHODS: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation. RESULTS: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors. CONCLUSIONS: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients.

Comorbid Conditions Are Associated With Cognitive Impairment in Native Hawaiians and Pacific Islanders.

We examined the association between comorbid conditions and mild cognitive impairment (MCI) in Native Hawaiians and Pacific Islanders (NHPI) (n = 54). Cross-sectional, self-reported questionnaires were utilized to collect demographic, comorbid conditions, and MCI (via the AD8 index) data. Separate logistic regression models were conducted to investigate the relationship between comorbid conditions and MCI, adjusting for other covariates. We found significantly increased odds of MCI in those reporting high blood pressure (OR = 5.27; 95% CI: [1.36, 20.46]; p = 0.016), high cholesterol (OR = 7.30; 95% CI: [1.90, 28.14], p = 0.004), and prediabetes or borderline diabetes (OR = 4.53; 95% CI: [1.27, 16.16], p = 0.02) compared with those not reporting these respective conditions. These data show that hypertension, hypercholesterolemia, and prediabetes are associated with MCI in the NHPI community, suggesting that preventive strategies to reduce chronic conditions may also potentially slow cognitive decline in underrepresented/understudied NHPI.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

[Relationship between hypercholesterolemia and osteoarthritis (preliminary results)].

AIM: To evaluate the relationship of hypercholesterolemia (HCE) with clinical, instrumental, and laboratory parameters in osteoarthritis (OA) in a multicenter, cross-sectional study. MATERIALS AND METHODS: The study included 183 patients aged 40-75 years, with a confirmed diagnosis of stage I-III OA (ACR) of the knee joints, who signed an informed consent. The mean age was 55.6±10.7 years (40 to 75), body mass index was 29.3±6.3 kg/m2, and disease duration was 5 [1; 10] years. For each patient, a case record form was filled out, including anthropometric indicators, medical history, clinical examination data, an assessment of knee joint pain according to VAS, WOMAC, KOOS and comorbidities. All patients underwent standard radiography and ultrasound examination of the knee joints and laboratory tests. RESULTS: HCE was detected in 59% of patients. Depending on its presence or absence, patients were divided into two groups. Patients were comparable in body mass index, waist and hip measurement, and disease duration but differed significantly in age. Individuals with elevated total cholesterol levels had higher VAS pain scores, total WOMAC and its components, an overall assessment of the patient's health, a worse KOOS index, and ultrasound findings (reduced cartilage tissue). HCE patients showed high levels of cholesterol, low-density lipoproteins, triglycerides, STX-II, and COMP (p<0.05). However, after stratification by age, many initial intergroup differences became insignificant, and differences in the WOMAC pain score persisted. CONCLUSION: The results of the study confirmed the high prevalence of HCE in OA patients (59%). Patients with OA and increased total cholesterol have more intense pain in the knee joints.

Geographic distribution of United States clinical trial sites utilized for guideline changing studies of cholesterol management.

BACKGROUND: This study aimed to evaluate the geographic distribution of United States (US) clinical trial sites utilizedfor guideline changing studies of cholesterol management. METHODS: Randomized trials evaluating pharmacologic interventions for cholesterol treatment and reporting location data (ie, zip code of trial sites) were identified. Location data was abstracted from ClinicalTrials.gov. RESULTS: Half of US counties were over 30 miles from a study site and, social determinants of health were more favorable in counties with versus without clinical trial sites. CONCLUSIONS: Stakeholders such as regulatory bodies andtrial sponsors should incentivize and support infrastructure that would enable a larger number of US counties to be utilized for clinical trial sites. TRIAL REGISTRATION: Not applicable.

Cholesterol Screening in Children: Is a Universal Approach Working?

PURPOSE OF REVIEW: Ample evidence supports that an individual's lifetime risk of atherosclerotic cardiovascular disease correlates to long-term, cumulative exposure to circulating cholesterol levels, beginning in childhood. Selective screening strategies based on family history fail to identify many children with hypercholesterolemia. Universal cholesterol screening in childhood is a worthwhile goal. However, cholesterol screening rates through childhood remain low. RECENT FINDINGS: Mounting evidence clarifies the barriers to cholesterol screening in children. Specific strategies to foster universal screening in childhood have been proposed. SUMMARY: We present an overview of the present state of childhood cholesterol screening, summarizing historical and contemporary guidelines and collating evidence of low adherence to current guidelines. We contend that novel approaches to universal cholesterol screening in childhood are warranted, and we present potential opportunities for improvement. We call for new and universal pediatric cholesterol screening guidelines.

The burden of hypercholesterolemia and ischemic heart disease in an ageing world.

Despite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability worldwide, with ischemic heart disease (IHD) being responsible for half of CVD deaths. Hypercholesterolemia is a major causal risk factor for IHD. Although the availability of effective cholesterol-lowering drugs largely increased in the last few years, we are still facing disparities in the awareness of dyslipidaemia as a CVD-associated risk factor and therefore in health expenditure among different world areas. Although no significant changes have been reported globally in the levels of plasma cholesterol in the last three decades, relevant differences among world areas according to their economic status can be observed. Only high-income countries have experienced an improvement in plasma lipid profile which translated into a substantial decrease in the deaths and disabilities due to IHD, whereas countries in other income groups showed no reduction or even an increase. As expected, most of the deaths for IHD attributable to high LDL-C occur in people aged 60 years and above, although significant differences can be observed according to income. Altogether these observations suggest the need for measures to reduce the gap in treating hypercholesterolemia among income groups, with special attention to women and older people.

Association of meal timing of energy, macronutrients and foods with hypercholesterolaemia in the US adults.

Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003-2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.