Differences between repeated lipid profile measurements in a tertiary hospital over a short time period.

BACKGROUND: Measurement of the plasma lipid profile, mainly low-density lipoprotein cholesterol (LDL-C), is widely used in the management of hospitalized patients as part of their cardiometabolic risk assessment. In common practice, LDL-C is calculated indirectly by the Friedewald equation. For many years, fasting of 8-14 h is needed to obtain an accurate lipid profile measurement, although recent guidelines do not necessitate it. The aim of this study was to find patients with two consecutive LDL-C measurements taken over a short time period on the same admission to see if a significant difference exists and to suggest reasons that may explain it. We also aim to define whether the difference between LDL-C calculated by the Friedewald equation is diminished while using the newer Martin/Hopkins, de Cordova or Sampson/NIH equations. METHODS: This was a retrospective cohort study performed in one medical center in Israel. In a five-year time period, 772 patients with two repeated LDL-C measurements taken on the same admission were found. The median time gap between tests was 2 days. Correlations between laboratory results and LDL-C measurements were determined. RESULTS: A total of 414 patients (53.6%) had a difference greater than the acceptable total error of 8.9% in LDL-C calculation using the Friedewald equation, with a mean 25.8% difference between the two tests. Newer LDL-C calculations showed less diversity. Non-HDL-C was found as the only variable with a major correlation with LDL-C results in all equations. A weaker correlation was found with HDL-C. Triglycerides showed an even weaker correlation, and glucose differences had no correlation with LDL-C differences. CONCLUSIONS: Repeated LDL-C measurements can vary widely, even during a short period of hospitalization. In this study, more than half of the patients had a significant difference between their consecutive LDL-C results. This wide difference between two consecutive tests was diminished using newer calculations, yet not well explained. The fasting state likely has no effect on LDL-C levels. The results of this study might emphasize that many factors influence LDL-C calculation, especially in the disease state. Further research is needed, especially in looking for a more accurate LDL-C calculation from existing formulas.

Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study.

PURPOSE: Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS: This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS: All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION: Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.

Rewriting DNA in the body lowers cholesterol.

Verve Therapeutics says its base-editing approach may help prevent heart disease in many people.

Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding trial.

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA's role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants' mean age was 35 years, 70% were women, the mean BMI was 28 kg/m2, and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: -12 mg/dl) as were total cholesterol (-16 mg/dl), HDL-C (-5 mg/dl), apoA-1 (-9 mg/dl) and apoB-100 (-5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.

Low-Density Lipoprotein Cholesterol Levels in Adults With Coronary Artery Disease in the US, January 2015 to March 2020.

This study uses National Health and Nutrition Examination Survey data to examine lipid control among adults in the US with coronary artery disease from January 2015 to March 2020.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment.

The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.

Clinical utility of lipid ratios as potential predictors of metabolic syndrome among the elderly population: Birjand Longitudinal Aging Study (BLAS).

BACKGROUND: Elderly adults are at higher risk of developing metabolic syndrome (MetS). The present study aims to investigate the relationship between lipid ratios and MetS in the elderly population. METHODS: This study was conducted on elderly population of Birjand during 2018-2019. The data of this study was driven from Birjand Longitudinal Aging Study (BLAS). The participants were selected based on multistage stratified cluster sampling. Patients were categorized into quartiles according to the lipid ratios (TG/HDL-C, LDL-C/HDL-C, non-HDL/HDL-C), and the relationship between lipid ratio quartiles and MetS was determined by Logistic Regression using Odds Ratio. Finally, the optimal cut-off for each lipid ratio in MetS diagnosis was calculated according to the Area Under the Curve (AUC). RESULTS: This study included 1356 individuals, of whom 655 were men and 701 were women. In our study, the crude prevalence of MetS was 792 (58%), including 543 (77.5%) women and 249 (38%) men. Increasing trends were observed in quartiles of all lipid ratios for TC, LDL-C, TG, and DBP. TG/HDL was also the best lipid ratio to diagnose the MetS, based on NCEP ATP III criteria. One unit increased in level of TG/HDL resulted in 3.94 (OR: 3.94; 95%CI: 2.48-6.6) and 11.56 (OR: 11.56; 95%CI: 6.93-19.29) increasing risk of having MetS in quartile 3 and 4 compared to quartile 1, respectively. In men and women, the cutoff for TG/HDL was 3.5 and 3.0, respectively. CONCLUSIONS: Our results showed that the TG/HDL-C is superior to the LDL-C/HDL-C and the non-HDL /HDL-C to predict MetS among the elderly adults.

Additive effect between homocysteine and low-density-lipoprotein cholesterol upon incidence of novel carotid plaque formation: data from a Chinese community-based cohort.

OBJECTIVE: Homocysteine (HCY) has been associated with carotid plaque in cross-sectional studies, but the prospective relationship between HCY and incident carotid plaque has not been well established. The purpose of this study was to investigate the association between HCY and incidence of novel carotid plaque in a Chinese community-based population without pre-existing carotid atherosclerosis and to assess the additive effect of HCY and low-density lipoprotein cholesterol (LDL-C) on the incidence of novel plaque. METHODS: At baseline, we measured HCY and other risk factors in subjects aged ≥ 40 years. All participants underwent carotid ultrasound examinations at baseline and after an average of 6.8 years of follow-up. Incidence of plaque was identified if plaque was absent at baseline, but plaque was detected at the end of follow-up. A total of 474 subjects were included in the analysis. RESULTS: The incidence of novel carotid plaque was 24.47%. Multivariate regression analyses showed that HCY was independently associated with a 1.05-fold-higher likelihood for incident novel plaque (adjusted odds ratio [OR] = 1.05, 95% confidence interval [CI]: 1.01-1.09, P = 0.008). Using tertile 1 and tertile 2 for reference, the top HCY tertile (T3) showed a 2.28-fold-higher likelihood for incident plaque (adjusted OR = 2.28, 95%CI: 1.33-3.93, P = 0.002). The combination of HCY T3 and LDL-C ≥ 3.4 mmol/L had the highest risk for novel plaque formation (adjusted OR = 3.63, 95%CI: 1.67-7.85, P = 0.001) compared to those without either condition. In the LDL-C ≥ 3.4 mmol/L subgroup, HCY was significantly associated with incidence of plaque (adjusted OR = 1.16, 95%CI: 1.04-1.28, P = 0.005, P-interaction = 0.023). CONCLUSION: In the Chinese community-based population, HCY was independently associated with the incidence of novel carotid plaque. There were additive effect between HCY and LDL-C on the incidence of plaque, the highest risk was observed in individuals with both high HCY levels and LDL-C ≥ 3.4 mmol/L. Our findings suggest that HCY may be a potential target for preventing the incidence of carotid plaque, particularly in individuals with elevated LDL-C levels.

Método indirecto para la verificación del intervalo de referencia del perfil lipídico / Indirect method for the verification of the lipid profile reference range

Introducción: La dislipidemia es uno de los problemas más frecuentes en los niños y adolescentes y su estudio es importante debido a su fuerte correlación con la enfermedad cardiovascular aterosclerótica en adultos. Muchos países desarrollaron valores de referencia nacionales investigando los lípidos séricos utilizando datos basados en la población nacional propia. Nuestro objetivo fue verificar el intervalo de referencia del perfil lipídico calculando las curvas de percentiles a través del método indirecto en nuestra población pediátrica. Materiales y métodos: Se analizaron los resultados de nuestra base de datos utilizando el método indirecto. Luego de aplicar filtros y criterios de exclusión se calcularon los percentiles 25, 50, 75, 95 y 99 para colesterol total (CT), colesterol HDL (C-HDL), colesterol no HDL (C-no-HDL), triglicéridos (TG) y colesterol LDL (C-LDL) y para el C-HDL además se calculó el percentil 10. El valor de referencia para el cambio (RCV) se utilizó para determinar si existía diferencia clínicamente significativa entre los valores de percentiles obtenidos y los utilizados en el consenso de la SAP. Resultados: No se evidenció diferencia clínicamente significativa contra los valores propuesto por la SAP, excepto para los TG para las edades 1,5,7 años en el percentil 95 y para la edad de 8 años en el percentil 75 y 95; para el C-HDL en el percentil 10 para las edades 1,16 y 17 años. Discusión: Se obtuvieron los percentiles de los lípidos y se compararon con los valores de referencia utilizados por el consenso en el que están basados las guías (AU)

Introduction: Dyslipidemia is one of the most common problems in children and adolescents and its study is important because of its strong correlation with atherosclerotic cardiovascular disease in adulthood. Many countries have developed national reference values investigating serum lipids using data based on their own national population. Our aim was to verify the lipid profile reference range by calculating percentile curves through the indirect method in our pediatric population. Materials and methods: The results of our database were analyzed using the indirect method. After applying filters and exclusion criteria, the 25th, 50th, 75th, 95th, and 99th percentiles were calculated for total cholesterol (TC), HDL cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), triglycerides (TG), and LDL cholesterol (LDL-C); for HDL-C, the 10th percentile was also calculated. The reference change values (RCV) were used to determine whether there was a clinically significant difference between the percentile values obtained and those used in the consensus of the Argentine Association of Pediatrics (SAP). Results: There was no clinically significant difference with the values proposed by the SAP, except for TG for ages 1, 5, and 7 years at the 95th percentile and for age 8 years at the 75th and 95th percentile; and for HDL-C at the 10th percentile for ages 1, 16, and 17 years. Discussion: Lipid percentiles were obtained and compared with the reference values used by the consensus on which the guidelines are based (AU)

Comparison of the accuracy of the Friedewald, Martin, and Sampson formulas to estimate very low levels of low-density lipoprotein cholesterol.

INTRODUCTION: The Martin (MF) and Sampson (SF) formulas have shown greater accuracy for low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL compared to the Friedewald formula (FF); however, some disagreement is maintained. Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are alternatives to assessing cardiovascular risk in patients with very low LDL-C. The objective was to evaluate the accuracy of FF, MF, and SF formulas to estimate LDL-C < 70 mg/dL vs. directly measured LDL-C (LDLd-C) and to compare non-HDL-C and Apo-B levels between the groups of patients with concordant vs. discordant LDL-C. MATERIAL AND METHODS: This was a prospective clinical study with measurements of lipid profile and LDLd-C in 214 patients with triglycerides < 400 mg/dL. For each formula, the estimated LDL-C was compared with the LDLd-C, and the correlation, the median difference, and the discordance rate were evaluated. Non-HDL-C and Apo-B levels were compared between the groups with concordant and discordant LDL-C. RESULTS: The estimated LDL-C was < 70 mg/dL in 130 (60.7%) patients by FF, 109 (50.9%) by MF, and 113 (52.8%) by SF. The strongest correlation was found between LDLd-C and Sampson estimated LDL-C (LDLs-C) (R2 = 0.778), followed by Friedewald-estimated LDL-C (LDLf-C) (R2 = 0.680) and Martin estimated LDL-C (LDLm-C) (R2 = 0.652). Estimated LDL-C < 70 mg/dL was lower than LDLd-C, with the largest median absolute difference (25-75th) of -15 (-19 to -10) with FF. For estimated LDL-C < 70 mg/dL, the discordant rate was 43.8%, 38.1%, and 35.1%, reaching for 62.3%, 50.9%, and 50% when LDL-C < 55 mg/dL by FF, SF, and MF, respectively. Patients in the discordant group presented significantly higher levels of non-HDL-C and ApoB for all 3 formulas (p < 0.001). CONCLUSION: FF was the most inaccurate formula to estimate very low LDL-C. Despite MF and SF showing better results, their frequency in underestimating LDL-C was still considerable. In patients with falsely low estimated LDL-C, apoB and non-HDL-C were significantly higher, reflecting its true high atherogenic burden.

Insulin resistance and body mass index are associated with TSPO PET in cognitively unimpaired elderly.

Metabolic risk factors are associated with peripheral low-grade inflammation and an increased risk for dementia. We evaluated if metabolic risk factors i.e. insulin resistance, body mass index (BMI), serum cholesterol values, or high sensitivity C-reactive protein associate with central inflammation or beta-amyloid (Aß) accumulation in the brain, and if these associations are modulated by APOE4 gene dose. Altogether 60 cognitively unimpaired individuals (mean age 67.7 years (SD 4.7); 63% women; 21 APOE3/3, 20 APOE3/4 and 19 APOE4/4) underwent positron emission tomography with [11C]PK11195 targeting TSPO (18 kDa translocator protein) and [11C]PIB targeting fibrillar Aß. [11C]PK11195 distribution value ratios and [11C]PIB standardized uptake values were calculated in a cortical composite region of interest typical for Aß accumulation in Alzheimer's disease. Associations between metabolic risk factors, [11C]PK11195, and [11C]PIB uptake were evaluated with linear models adjusted for age and sex. Higher logarithmic HOMA-IR (standardized beta 0.40, p = 0.002) and BMI (standardized beta 0.27, p = 0.048) were associated with higher TSPO availability. Voxel-wise analyses indicated that this association was mainly seen in the parietal cortex. Higher logarithmic HOMA-IR was associated with higher [11C]PIB (standardized beta 0.44, p = 0.02), but only in APOE4/4 homozygotes. BMI and HOMA-IR seem to influence TSPO availability in the brain.

Evaluation of Friedewald's Formula for Plasma LDL-Cholesterol Estimation.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can contribute to atherosclerosis if it is oxidized within the walls of arteries. Therefore, LDL-C plays an important role in cardiovascular disease risk assessment and prevention. The current study aims to evaluate the validity of Friedewald's formula in the Taiwanese population. METHODS: In this analytical cross-sectional study, a data set containing 31,729 results was used and lipid profiles of all samples were measured using the Beckman Coulter AU680 clinical chemistry analyzer. This study was conducted from September 2016 to August 2019. RESULTS: The agreement between the direct and calculated LDL-C was significant with Pearson's correlation coefficient (r) of 0.904 (p < 0.001). Mean LDL-C levels were 99.3 ± 32.8 mg/dL and 95.3 ± 37.6 mg/dL for direct and calculated LDC-C, respectively. CONCLUSIONS: Good agreement was observed between direct and calculated LDC-C. Therefore, it can be concluded that Friedewald's formula is applicable in LDL-C estimation when the direct method is not affordable.

Grado de consecución de los objetivos lipídicos a largo plazo en una cohorte de pacientes con síndrome coronario agudo en práctica clínica real / Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice

Introduction and objectives According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. Methods This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. Results A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88–111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. Conclusions Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7–10 years), especially in patients with recurrent ACS (AU)

Introducción y objetivos Según los recientes estudios epidemiológicos europeos, el grado de control lipídico de los pacientes de muy alto riesgo vascular es subóptimo. En este estudio se han analizado las características epidemiológicas, los factores de riesgo cardiovascular, el perfil lipídico, la recurrencia y el grado de consecución de los objetivos lipídicos a largo plazo, según las Guías ESC/EAS, en una cohorte de pacientes con síndrome coronario agudo (SCA), en condiciones de práctica clínica real. Métodos Estudio de cohorte retrospectivo de los pacientes con diagnóstico de SCA ingresados en la unidad coronaria de un hospital de tercer nivel, entre el 1 de enero de 2012 y el 31 de diciembre de 2015, y seguidos hasta marzo de 2022. Resultados Se estudiaron 826 pacientes. Durante el periodo de seguimiento se observó una mayor prescripción de terapia hipolipemiante combinada, principalmente estatinas de alta y moderada intensidad y ezetimibe. A los 24 meses del SCA, un 33,6% de los pacientes vivos tenían un LDL < 70 mg/dl y en un 9,3% los niveles eran < 55 mg/dl. Al final del seguimiento (101 [88–111] meses), las correspondientes cifras eran del 54,5 y 21,1%. Un 22,1% de los pacientes presentaron un evento coronario recurrente, y solamente un 24,6% de ellos alcanzaron un nivel de LDL < 55 mg/dl. Conclusiones El cumplimiento de los objetivos recomendados por las Guías ESC/EAS en pacientes con SCA, es subóptimo, tanto a los 2 años como a largo plazo (7-10 años) desde el evento, y en especial en los pacientes con SCA recurrente (AU)

The correlation between the serum LDL-C/Apo B ratio and lumbar bone mineral density in young adults.

BACKGROUND: Numerous studies have confirmed that atherosclerosis is related to osteoporosis (OP), and patients with atherosclerosis are more prone to OP. The ratio of low-density lipoprotein cholesterol (LDL-C) to apolipoprotein B (Apo B) is the valid indicator of atherosclerosis. Nevertheless, conclusions regarding relation between LDL-C/Apo B ratio and bone mineral density (BMD) are still lacking. As a result, this study concentrated on investigating the relationship between LDL-C/Apo B ratio and lumbar BMD in the young adult population according to the National Health and Nutrition Examination Survey (NHANES). METHODS: Information of 2027 young adults (age 20-40 years) from NHANES database was obtained for this cross-sectional study. The correlation between serum LDL-C/Apo B ratio and lumbar BMD was explored through weighted multiple stratified linear regression, while the smooth curve fitting model was utilized for analyzing nonlinear relation. In the nonlinear relation, the inflection point was calculated by saturation threshold analysis. The weighted two-piecewise linear regression model was constructed. RESULTS: After covariates were adjusted, the relation between serum LDL-C/Apo B ratio and lumbar BMD varied by sex (males: ß = -0.0126, 95% CI -0.0892, 0.0640; females: ß = 0.0322, 95% CI -0.0367, 0.1011). By performing age-stratified subgroup analysis, the association also varied by age and sex. Males aged 20-30 years presented a negative trend (ß = -0.0570, 95% CI -0.1656, 0.0517), and males with the age of 31-40 years showed a positive trend (ß = 0.0810, 95% CI -0.0312, 0.1931). Women showed a positive trend by age (females of 20-30 years: ß = 0.0051, 95% CI -0.0935, 0.1036; females of 31-40 years: ß = 0.0265, 95% CI -0.0767, 0.1296). In race-stratified subgroup analysis, the relations varied by sex and race. To be specific, non-Hispanic black males showed a negative trend (ß = -0.0754, 95% CI -0.2695, 0.1188), and males of other races exhibited a positive trend. The trend was positive for women of all races. CONCLUSION: Differences were detected in the association between serum LDL-C/Apo B ratio and lumbar BMD among cases aged 20-40 years across sex, age, and race/ethnicity. In addition, the inflection points in U-shaped relationships were also calculated.

The causal effects of lipid traits on kidney function in Africans: bidirectional and multivariable Mendelian-randomization study.

BACKGROUND: Observational studies have investigated the effect of serum lipids on kidney function, but these findings are limited by confounding, reverse causation and have reported conflicting results. Mendelian randomization (MR) studies address this confounding problem. However, they have been conducted mostly in European ancestry individuals. We, therefore, set out to investigate the effect of lipid traits on the estimated glomerular filtration rate (eGFR) based on serum creatinine in individuals of African ancestry. METHODS: We used the two-sample and multivariable Mendelian randomization (MVMR) approaches; in which instrument variables (IV's) for the predictor (lipid traits) were derived from summary-level data of a meta-analyzed African lipid GWAS (MALG, n = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (n = 13,612) & the Africa Wits-IN-DEPTH partnership for Genomics studies (AWI-Gen) dataset (n = 10,603). The outcome IV's were computed from the eGFR summary-level data of African-ancestry individuals within the Million Veteran Program (n = 57,336). A random-effects inverse variance method was used in our primary analysis, and pleiotropy was adjusted for using robust and penalized sensitivity testing. The lipid predictors for the MVMR were high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG). FINDINGS: We found a significant causal association between genetically predicted low-density lipoprotein (LDL) cholesterol and eGFR in African ancestry individuals ß = 1.1 (95% CI [0.411-1.788]; p = 0.002). Similarly, total cholesterol (TC) showed a significant causal effect on eGFR ß = 1.619 (95% CI [0.412-2.826]; p = 0.009). However, the IVW estimate showed that genetically predicted HDL-C ß = -0.164, (95% CI = [-1.329 to 1.00]; p = 0.782), and TG ß = -0.934 (CI = [-2.815 to 0.947]; p = 0.33) were not significantly causally associated with the risk of eGFR. In the multivariable analysis inverse-variance weighted (MVIVW) method, there was evidence for a causal association between LDL and eGFR ß = 1.228 (CI = [0.477-1.979]; p = 0.001). A significant causal effect of Triglycerides (TG) on eGFR in the MVIVW analysis ß = -1.3 ([-2.533 to -0.067]; p = 0.039) was observed as well. All the causal estimates reported reflect a unit change in the outcome per a 1 SD increase in the exposure. HDL showed no evidence of a significant causal association with eGFR in the MVIVW method (ß = -0.117 (95% CI [-1.252 to 0.018]; p = 0.840)). We found no evidence of a reverse causal impact of eGFR on serum lipids. All our sensitivity analyses indicated no strong evidence of pleiotropy or heterogeneity between our instrumental variables for both the forward and reverse MR analysis. INTERPRETATION: In this African ancestry population, genetically predicted higher LDL-C and TC are causally associated with higher eGFR levels, which may suggest that the relationship between LDL, TC and kidney function may be U-shaped. And as such, lowering LDL_C does not necessarily improve risk of kidney disease. This may also imply the reason why LDL_C is seen to be a poorer predictor of kidney function compared to HDL. In addition, this further supports that more work is warranted to confirm the potential association between lipid traits and risk of kidney disease in individuals of African Ancestry. FUNDING: Wellcome (220740/Z/20/Z).

Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.

Association between Dietary Patterns and Serum Low Density Lipoprotein Cholesterol in Japanese Women and Men: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

AIMS: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. METHODS: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. RESULTS: We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001). CONCLUSION: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.