Causal relationship between depression and hypercholesterolemia: A bidirectional 2-sample Mendelian randomization study.

Although observational studies have found both a positive and negative association between depression and hypercholesterolemia, the findings are mixed and contradictory. To our knowledge, this is the first study that employs the bidirectional Mendelian randomization (MR) and multivariable MR analysis with extensive genome-wide association studies (GWAS) data to examine the causal effect between depression and hypercholesterolemia. Using summary statistics obtained from GWAS of individuals with European ancestry, we utilize a bidirectional 2-sample MR approach to explore the potential causal association between hypercholesterolemia and depressive symptoms. Multivariable Mendelian randomization analysis was used to examine whether the direct causal effect of depression on the risk of hypercholesterolemia can be affected by traits associated with the increased risk of hypercholesterolemia. This MR analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted mode, and weighted median methods. Data on the summary level of depression were acquired from a GWAS that involved 500,199 participants. We used summary GWAS datasets for hypercholesterolemia including 206,067 participants. We also used another GWAS databases of hypercholesterolemiat (n = 463,010) to validate our results. By utilizing IVW, it was discovered that there is a possibility of a 31% rise in the risk of hypercholesterolemia due to depression (OR = 1.31, 95% CI = 1.10-1.57, P = .002). We found a consistent causal effect of depression on hypercholesterolemia from the IVW analyses using different hypercholesterolemia datasets. After adjustment of smoking, physical activity, and obesity, there remains significant causal relationship between depression and hypercholesterolemia (OR = 1.25, 95% CI = 1.01-1.54, P = .040). However, we did not find any evidence indicating that hypercholesterolemia leads to depression in the opposite direction. Directional pleiotropy was not observed in the MR-Egger regression analysis. Additionally, the MR-PRESSO analysis validated these discoveries. Neither the leave-one-out sensitivity test nor the funnel plots revealed any outliers. In both the unadjusted and adjusted estimates, depression has a consistent direct causal effect on hypercholesterolemia. Our study has led to an improved comprehension of the causal connections between hypercholesterolemia and depression, which could aid in the prevention and treatment of hypercholesterolemia.

Dyslipidemia and associated factors among adult cardiac patients: a hospital-based comparative cross-sectional study.

BACKGROUND: Atherosclerotic vascular diseases are a leading global cause of morbidity and mortality. Dyslipidemia, a major modifiable risk factor for cardiovascular disease, remains poorly understood among adult cardiac patients in in the study area. This study aims to determine the prevalence of dyslipidemia and identify associated factors in this population. METHODS: Hospital-based comparative cross-sectional study was conducted from May to August 2021. A total of 319 participants (153 cardiac cases, 166 healthy controls, aged ≥ 18) were included in the study. Socio-demographic, anthropometric, behavioral, and clinical data were collected using the WHO STEPS survey instrument through systematic sampling. Overnight fasting blood samples were obtained, and serum lipid profiles were analyzed using a COBAS 6000 analyzer. Data were analyzed with SPSS version 20.0, employing bivariable and multivariable logistic regression. Statistical significance was set at p < 0.05. RESULTS: The overall prevalence of dyslipidemia, encompassing at least one lipid abnormality, was 80.3% among 256 participants. Among cardiac cases, the prevalence rates were as follows: 72.5% for low HDL-cholesterol, 12.4% for hypercholesterolemia, 9.8% for elevated LDL-cholesterol, and 30.1% for hypertriglyceridemia. In controls, corresponding rates were 69.9%, 9.6%, 7.2%, and 32.5%. Significant factors linked to low HDL- cholesterol were female gender (AOR: 2.8, 95% CI 1.7-4.7) and obesity (AOR: 2.8, 95% CI 1.1-7.5). Abdominal obesity was associated with hypercholesterolemia (AOR: 5.2, 95% CI 1.9-14.3) and elevated LDL-cholesterol (AOR: 5.1, 95% CI 1.6-15.8). High blood pressure, overweight, and abdominal obesity were significantly linked to hypertriglyceridemia (p < 0.05). CONCLUSION: Dyslipidemia was high among the study participants. Overweight, obesity, central adiposity, and high blood pressure were significantly associated with dyslipidemia in cardiac patients. This alarms the need for lipid profile assessment for patients periodically, with treatment follow-up to monitor any rising patterns and cardiovascular-related risks.

Social inequality in prevalence of NCD risk factors: a cross-sectional analysis from the population-based Tromsø Study 2015-2016.

OBJECTIVE: We aimed to examine associations between educational level, serving as an indicator of socioeconomic position, and prevalence of WHO-established leading behavioural and biological risk factors for non-communicable diseases (NCDs), in middle-aged to older women and men. DESIGN: Population-based cross-sectional study. SETTING: All inhabitants of the municipality of Tromsø, Norway, aged ≥40 years, were invited to the seventh survey (2015-2016) of the Tromsø Study; an ongoing population-based cohort study. PARTICIPANTS: Of the 32 591 invited; 65% attended, and a total of 21 069 women (53%) and men aged 40-99 years were included in our study. OUTCOME MEASURES: We assessed associations between educational level and NCD behavioural and biological risk factors: daily smoking, physical inactivity (sedentary in leisure time), insufficient fruit/vegetable intake (<5 units/day), harmful alcohol use (>10 g/day in women, >20 g/day in men), hypertension, obesity, intermediate hyperglycaemia and hypercholesterolaemia. These were expressed as odds ratios (OR) per unit decrease in educational level, with 95% CIs, in women and men. RESULTS: In women (results were not significantly different in men), we observed statistically significant associations between lower educational levels and higher odds of daily smoking (OR 1.69; 95% CI 1.60 to 1.78), physical inactivity (OR 1.38; 95% CI 1.31 to 1.46), insufficient fruit/vegetable intake (OR 1.54, 95% CI 1.43 to 1.66), hypertension (OR 1.25; 95% CI 1.20 to 1.30), obesity (OR 1.23; 95% CI 1.18 to 1.29), intermediate hyperglycaemia (OR 1.12; 95% CI 1.06 to 1.19), and hypercholesterolaemia (OR 1.07; 95% CI 1.03 to 1.12), and lower odds of harmful alcohol use (OR 0.75; 95% CI 0.72 to 0.78). CONCLUSION: We found statistically significant educational gradients in women and men for all WHO-established leading NCD risk factors within a Nordic middle-aged to older general population. The prevalence of all risk factors increased at lower educational levels, except for harmful alcohol use, which increased at higher educational levels.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

BACKGROUND: Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. METHODS AND RESULTS: Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). CONCLUSIONS: Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

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.

Assessment of hypercholesterolemia prevalence and its demographic variations in the Republic of Kazakhstan.

Hypercholesterolemia is a major risk factor for cardiovascular disease, the leading cause of death in Kazakhstan. Understanding its prevalence is vital for effective public health planning and interventions. This study aimed to assess the scale of hypercholesterolemia in the Republic of Kazakhstan and to identify differences among distinct population groups. A cross-sectional study involving 6720 participants (a nationally representative survey.) aged 18-69 was conducted from October 2021 to May 2022 across all 17 regions of Kazakhstan. The magnitude of hypercholesterolemia was 43.5%. Cholesterol levels were determined through blood biochemical analysis. Age, sex, geographic location, and ethnicity served as covariates. The majority of participants (65.49%) were from urban areas with an almost equal gender distribution (50.07% male and 49.93% female). The predominant age groups were 18-29 years (25.71%) and 30-39 years (25.12%), and 65.09% identified as Kazakh. The prevalence increased with age, with the 60-69 age group showing the highest rate at 71.14%. Women had slightly higher rates than men. Geographical differences were evident, with regions like Astana city and Almaty region showing significant disparities. Kazakhs had a lower rate compared to other ethnicities. Age, region, and BMI were significant predictors for hypercholesterolemia in both binary and multivariate logistic regression analyses. The study revealed a significant prevalence of hypercholesterolemia in Kazakhstan, with increasing age as a major determinant. Women, especially those over 50, and certain regions showed higher cholesterol levels. The disparities observed across regions and ethnicities suggest the need for targeted public health interventions to address this pressing health concern.

Red Yeast Rice and Statin Therapy in Patients with Hypercholesterolemia and the Comorbidities: A Retrospective Cohort Study on Lipid-Lowering Effects and Cardiovascular Outcomes.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of [Formula: see text] years, absence of RYR or statin treatment, and a treatment duration of [Formula: see text] days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin ([Formula: see text]) or combined use ([Formula: see text]) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group ([Formula: see text]) and increased glycohemoglobin levels in the statin group at the three-month mark ([Formula: see text]). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all [Formula: see text]). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted.

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.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020.

BACKGROUND AND AIMS: Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. METHODS: Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. RESULTS: A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. CONCLUSIONS: Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

Perfil clínico de la hipercolesterolemia severa en 156.000 adultos en atención primaria / Clinical profile of severe hypercholesterolemia in 156.000 adults in primary care

Objetivo Estimar la frecuencia y el perfil clínico de la hipercolesterolemia severa (HS) y del fenotipo de hipercolesterolemia familiar (HF) en el ámbito de atención primaria, en un área sanitaria de la comunidad de Madrid (CAM). Material y métodos Estudio transversal, multicéntrico de sujetos con tarjeta sanitaria adscritos a 69 centros de salud (área NorOeste/CAM). Se definió HS como colesterol ≥300mg/dl o colesterol-LDL ≥220mg/dl en alguna analítica realizada (1-1-2018 a 30-12-2021), y fenotipo de HF como cLDL ≥240mg/dl (≥160mg/dl si tratamiento hipolipemiante), con triglicéridos <200mg/dl y TSH <5μIU/ml. Resultados Se analizaron 156.082 adultos ≥18años con perfil lipídico disponible. 6.187 sujetos tenían HS (3,96% de las analíticas estudiadas; IC95%: 3,87-4,06%). El tiempo medio de evolución del diagnóstico de hiperlipemia en la historia clínica informatizada fue 10,8años; el 36,5% tenían hipertensión, el 9,5%, diabetes, y el 62,9%, sobrepeso/obesidad. El 83,7% tomaban hipolipemiantes (65,7% de baja/moderada y 28,6% de alta/muy-alta intensidad). El 6,1% tenían enfermedad cardiovascular (94,2% tratados con hipolipemiantes), con colesterol LDL <55, <70 y <100mg/dl de 1,8%, 5,8% y 20,2%, respectivamente (vs 1%, 2,3% y 11,2% si no había enfermedad cardiovascular). Mil seiscientos sujetos tenían fenotipo de HF (IC95%: 1,03%, 0,98-1,08%). Conclusiones Cuatro de cada 100 pacientes analizados en atención primaria tienen HS. Hay un elevado nivel de tratamiento farmacológico, pero de insuficiente intensidad, y escaso logro de objetivos terapéuticos. Uno de cada 100 tiene fenotipo de HF. La identificación de ambas situaciones por registros informatizados permitiría su detección más precisa y precoz y establecer estrategias preventivas cardiovasculares. (AU)

Objective To examine the frequency of severe hypercholesterolemia (HS) and its clinical profile, and the phenotype of familial hypercholesterolemia (FH), in the primary-care setting in a large health area of the Community of Madrid (CAM). Material and methods Multicenter study of subjects with a health card assigned to 69 health centers (Northwest/CAM area). HS was defined as cholesterol ≥300mg/dL or LDL-cholesterol ≥220mg/dL in any analysis performed (1-1-2018 to 12-30-2021); and FH phenotype as c-LDL ≥240mg/dL (≥160mg/dL if lipid-lowering treatment) with triglycerides <200mg/dL and TSH <5μIU/mL. Results 156,082 adults ≥18years with an available lipid profile were analyzed. 6187 subjects had HS (3.96% of the laboratory tests studied, 95%CI: 3.87-4.06%). The mean evolution time of the diagnosis of hyperlipidemia in the computerized clinical record was 10.8years, 36.5% had hypertension, 9.5% diabetes and 62.9% overweight/obesity. 83.7% were taking lipid-lowering drugs (65.7% low/moderate and 28.6% high/very high intensity). 6.1% had cardiovascular disease (94.2% treated with lipid-lowering agents), with LDL-cholesterol <55, <70 and <100mg/dL of 1.8%, 5.8% and 20.2%, respectively (vs. 1%, 2.3% and 11.2% if no cardiovascular disease). 1600 subjects had FH phenotype (95%CI: 1.03%, 0.98-1.08%). Conclusions Four out of 100 patients analyzed in primary care have HS, with high treatment level, but insufficient intensity, and poor achievement of treatment goals. One in 100 have the FH phenotype. The identification of both dyslipidemias by computerized records would allow their more precise and early detection and establish cardiovascular preventive strategies. (AU)

Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults.

OBJECTIVE: To evaluate the contemporary trends of lipid concentrations, cholesterol evaluation, hypercholesterolemia awareness, and statin use among individuals with severe dyslipidemia (low-density lipoprotein cholesterol [LDL-C] level ≥190 mg/dL) between 2011 and 2020. PATIENTS AND METHODS: This serial cross-sectional analysis included nonpregnant adults ≥20 years of age from the National Health and Nutrition Examination Survey between 2011 and 2020. Age-adjusted weighted trends of LDL-C, triglycerides, cholesterol evaluation in the past 5 years, hypercholesterolemia awareness, and documented statin use among individuals with severe dyslipidemia were estimated. RESULTS: Among 24,722 participants included, the prevalence of severe dyslipidemia was 5.4% (SE: 0.2%) which was stable across the study period (Ptrend=.78). Among individuals with severe dyslipidemia (mean age: 55.3 [SE: 0.7] years; 52.2% females; 68.8% non-Hispanic White), LDL-C (224.3 [SE: 4.2] mg/dL in 2011-2012 to 224.2 [SE: 4.6] mg/dL in 2017-2020; Ptrend =.83), and triglyceride (123.3 [SE: 1.1] mg/dL in 2011-2012 to 101.8 [SE: 1.1] mg/dL in 2017-2020; Ptrend=.13), levels remained stable from 2011 to 2020. The rates of cholesterol evaluation in the past 5 years (72.0% [SE: 5.7%] in 2011-2012 to 78.0% [SE: 4.8%] in 2017-2020; Ptrend=.91), hypercholesterolemia awareness (48.1% [SE: 5.5%] in 2011-2012 to 51.9% [SE: 5.8%] in 2017- 2020; Ptrend=.77), and documented statin use (34.7% [SE: 4.5%] in 2011-2012 to 33.4% [SE: 4.0%] in 2017-2020; Ptrend=.28) remained stagnant in individuals with severe dyslipidemia between 2011 and 2020. CONCLUSION: Among individuals with severe dyslipidemia, cholesterol evaluation and hypercholesterolemia awareness rates were stable at ∼75% and ∼50% in the past decade. Only ∼34% of individuals with severe dyslipidemia took statins between 2011 and 2020, which likely contributed to the stable LDL-C levels noted across the study period. Further investigations into the determinants of statin use and adherence to statins are needed.

Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study.

BACKGROUND: Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment. METHODS AND RESULTS: Eligible patients were those aged ≥75 years who had low-density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid-lowering drugs. Participants were randomly assigned into a diet-only or diet-plus-ezetimibe group. Baseline and 24-week follow-up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow-up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30-1.17), 0.44 (95% CI, 0.21-0.94), and 0.44 (95% CI, 0.21-0.93), respectively (trend P=0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed. CONCLUSIONS: The KEEP study indicated that higher campesterol levels without lipid-lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe. REGISTRATION: URL: https://www.umin.ac.jp; unique identifier: UMIN000017769.

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.

Low-Density Lipoprotein Cholesterol and Statin Usage Are Associated With Rates of Pseudarthrosis Following Single-Level Posterior Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the relationships of low-density lipoprotein cholesterol and statin usage with pseudarthrosis following single-level posterior or transforaminal lumbar interbody fusion (PLIF/TLIF). SUMMARY OF BACKGROUND DATA: Hypercholesterolemia can lead to atherosclerosis of the segmental arteries, which branch into vertebral bone through intervertebral foramina. According to the vascular hypothesis of disc disease, this can lead to ischemia of the lumbar discs and contribute to lumbar degenerative disease. Yet, little has been reported regarding the effects of cholesterol and statins on the outcomes of lumbar fusion surgery. MATERIALS AND METHODS: TriNetX, a global federated research network, was retrospectively queried to identify 52,140 PLIF/TLIF patients between 2002 and 2021. Of these patients, 2137 had high cholesterol (≥130 mg/dL) and 906 had low cholesterol (≤55 mg/dL). Perioperatively, 18,275 patients used statins, while 33,415 patients did not. One-to-one propensity score matching for age, sex, race, and comorbidities was conducted to balance the analyzed cohorts. The incidence of pseudarthrosis was then assessed in the matched cohorts within the six-month, one-year, and two-year postoperative periods. RESULTS: After propensity score matching, high-cholesterol patients had greater odds of developing pseudarthrosis six months [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.28-2.33], one year (OR: 1.59, 95% confidence interval (CI): 1.20-2.10), and two years (OR: 1.57, 95% CI: 1.20-2.05) following a PLIF/TLIF procedure. Patients with statin usage had significantly lower odds of developing pseudarthrosis six months (OR: 0.74, 95% CI: 0.69-0.79), one year (OR: 0.76, 95% CI: 0.71-0.81), and two years (OR: 0.77, 95% CI: 0.72-0.81) following single-level PLIF/TLIF. CONCLUSIONS: The findings suggest that patients with hypercholesterolemia have an increased risk of developing pseudarthrosis following PLIF/TLIF while statin use is associated with a decreased risk. The data presented may underscore an overlooked opportunity for perioperative optimization in lumbar fusion patients, warranting further investigation in this area.

Clinical profile of severe hypercholesterolemia in 156,000 adults in primary care. / Perfil clínico de la hipercolesterolemia severa en 156.000 adultos en atención primaria.

OBJECTIVE: To examine the frequency of severe hypercholesterolemia (HS) and its clinical profile, and the phenotype of familial hypercholesterolemia (FH), in the primary-care setting in a large health area of the Community of Madrid (CAM). MATERIAL AND METHODS: Multicenter study of subjects with a health card assigned to 69 health centers (Northwest/CAM area). HS was defined as cholesterol ≥300mg/dL or LDL-cholesterol ≥220mg/dL in any analysis performed (1-1-2018 to 12-30-2021); and FH phenotype as c-LDL ≥240mg/dL (≥160mg/dL if lipid-lowering treatment) with triglycerides <200mg/dL and TSH <5µIU/mL. RESULTS: 156,082 adults ≥18years with an available lipid profile were analyzed. 6187 subjects had HS (3.96% of the laboratory tests studied, 95%CI: 3.87-4.06%). The mean evolution time of the diagnosis of hyperlipidemia in the computerized clinical record was 10.8years, 36.5% had hypertension, 9.5% diabetes and 62.9% overweight/obesity. 83.7% were taking lipid-lowering drugs (65.7% low/moderate and 28.6% high/very high intensity). 6.1% had cardiovascular disease (94.2% treated with lipid-lowering agents), with LDL-cholesterol <55, <70 and <100mg/dL of 1.8%, 5.8% and 20.2%, respectively (vs. 1%, 2.3% and 11.2% if no cardiovascular disease). 1600 subjects had FH phenotype (95%CI: 1.03%, 0.98-1.08%). CONCLUSIONS: Four out of 100 patients analyzed in primary care have HS, with high treatment level, but insufficient intensity, and poor achievement of treatment goals. One in 100 have the FH phenotype. The identification of both dyslipidemias by computerized records would allow their more precise and early detection and establish cardiovascular preventive strategies.

Beyond cardiovascular risk: Implications of Familial hypercholesterolemia on cognition and brain function.

Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly prevalent in the population. Besides being an important causative factor of cardiovascular diseases, FH has been considered an early risk factor for Alzheimer's disease. Cognitive and emotional behavioral impairments in LDL receptor knockout (LDLr-/-) mice are associated with neuroinflammation, blood-brain barrier dysfunction, impaired neurogenesis, brain oxidative stress, and mitochondrial dysfunction. Notably, today, LDLr-/- mice, a widely used animal model for studying cardiovascular diseases and atherosclerosis, are also considered an interesting tool for studying dementia. Here, we reviewed the main findings in LDLr-/- mice regarding the relationship between FH and brain dysfunctions and dementia development.

Serious Adverse Events of Inclisiran in Patients With Hypercholesterolemia, a Meta-Analysis of ORION Trials.

BACKGROUND: Several studies have been conducted over the years to find an effective and safe therapeutic agent to treat hypercholesterolemia. Inclisiran is a novel drug being studied for its efficacy and safety in reducing low-density lipoprotein cholesterol levels in patients to reduce the risk of cardiovascular diseases. No previous study was done to review the trials for the serious adverse events of this drug. The primary objective of this research is to investigate the incidence of serious adverse events of this drug. DESIGN: A systematic review and meta-analysis of clinical trials is performed. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov, from their inception till July 3, 2023, was performed for ORION trials, studying the efficacy and safety of inclisiran. The random-effects model was used in the meta-analysis to provide a pooled proportion of serious adverse events. The risk of bias in each study was assessed by the Cochrane Risk of Bias Tool. RESULTS: From 319 studies searched from the databases, only 8 relevant articles remained after a detailed evaluation. These studies, having a total of 4981 patients, were involved in the analysis, with a pooled estimate showing a nonsignificant incidence of serious adverse events. Each adverse event was studied individually, and product issues and endocrine disorders had the highest odds ratio among them. All included studies were classified as moderate quality. CONCLUSION: Following systematic review and meta-analysis, we found no significant differences in any serious adverse events following the administration of inclisiran. However, larger ongoing trials will provide additional data to evaluate the safety profile of this agent.

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.

Does Awareness of Malaysian Healthy Plate Associate with Adequate Fruit and Vegetable Intake among Malaysian Adults with Non-Communicable Diseases?

The healthy eating plate concept has been introduced in many countries, including Malaysia, as a visual guide for the public to eat healthily. The relationship between Malaysian Healthy Plate (MHP) and adequate fruit and vegetable (FV) intake among morbid Malaysian adults is unknown. Hence, we investigated the relationship between awareness of the MHP and FV intake among morbid Malaysian adults. National survey data on 9760 morbid Malaysian adults aged 18 years and above were analyzed. The relationship between awareness of MHP and FV intake among Malaysian adults with obesity, diabetes mellitus, hypertension, and hypercholesterolemia were determined using multivariable logistic regression controlling for sociodemographic characteristics and lifestyle risk factors. Our data demonstrated that MHP awareness is associated with adequate FV intake among the Malaysian adults with abdominal obesity (adjusted odds ratio (aOR): 1.86, 95% confidence interval (CI): 1.05-3.29), diabetes mellitus (aOR: 4.88, 95% CI: 2.13-22.18), hypertension (aOR: 4.39, 95% CI: 1.96-9.83), and hypercholesterolemia (aOR: 4.16, 95% CI: 1.48-11.72). Our findings indicated the necessity for ongoing efforts by policymakers, healthcare professionals, and nutrition educators to promote the concept of MHP and ensure that morbid Malaysian adults consume a sufficient intake of FV or adopt a healthy eating pattern to achieve and maintain optimal health.

[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.