Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors.

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Association between gamma glutamyl transpeptidase to HDL-Cholesterol (GGT/HDL-C) ratio and metabolic syndrome resolution after sleeve gastrectomy.

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p = .019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p = .038) showed a significant association with the resolution of MetS. CONCLUSION: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

BACKGROUND: A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. METHODS: We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70 years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. RESULTS: Of the participants who reached the age of 70 years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. CONCLUSION: These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Association between lipid profiles and cigarette smoke among adults in the Persian cohort (Shahedieh) study.

OBJECTIVES: Exposure to cigarette smoke introduces a large amount of nicotine into the bloodstream through the lungs. So, smoking can be a risk factor for many diseases. The present study was conducted to investigate the effect of active and passive cigarette smoke on the blood lipid profile and dyslipidemia. METHODS: This cross-sectional study was performed on 5052 individuals who participated in the recruitment phase of the Shahedieh cohort study. A logistic regression model was used to investigate the relationship between smoking exposure status and lipid profiles. RESULTS: The prevalence of abnormal low-density lipoprotein-cholesterol (LDL-C), abnormal HDL-C, abnormal total cholesterol (TC), abnormal triglyceride (TG), and dyslipidemia were 254 (5.00%), 562 (11.10%), 470 (9.30%), 1008 (20.00%), and 1527 (30.20%), respectively. Adjusting for confounders, it was observed that current smokers had higher odds of having abnormal HDL-C [OR (95% CI), 2.90 (2.28-3.69)], abnormal TG [OR (95% CI), 1.71 (1.38-2.13)] and dyslipidemia [OR (95% CI), 1.86 (1.53-2.25)]. Ex-smokers also had greater odds of abnormal HDL-C [OR (95% CI), 1.51 (1.06-2.16)] compared to non-smokers who were not exposed to cigarette smoke. CONCLUSIONS: The findings indicated that current smokers had higher TG and lower HDL. So, necessary measures should be taken to reduce smoking. The findings also showed that the prevalence of abnormal TG and HDL in ex-smokers was lower than in current smokers. Therefore, the existence of incentive policies to quit smoking seems necessary.

Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study.

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Biomarkers of lipid metabolism in gastric cancer: a case control study.

BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer. METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected. RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage. CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort.

BACKGROUND/AIMS: The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. METHODS: This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65-2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10-1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50-59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70-2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84-2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29-6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10-1.93). This association was similarly observed in Model III. CONCLUSIONS: Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.

Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study.

BACKGROUND: Surgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia. METHODS: A retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery. RESULTS: Noteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251). CONCLUSIONS: Oesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.

Longitudinal study of the impact of the COVID-19 pandemic on diet and physical activity among Latinos of Mexican ancestry.

BACKGROUND: The COVID-19 pandemic caused societal disruption in the United States and most of the world, affecting many aspects of life, including healthcare and health-related behaviors such as diet, food security, and physical activity. Communities with economic and health disparities may have been particularly affected. This study was undertaken to determine how conditions in the early pandemic (January, 2021-February, 2022) affected Latino patients of Mexican Ancestry at high risk of type 2 diabetes mellitus who participated in El Banco por Salud biobank project in Tucson, Arizona. METHODS: Baseline, prepandemic measurements were available in 17, 21, and 60 patients with normal hemoglobin A1c (HbA1c), prediabetes, and type 2 diabetes, respectively. RESULTS: People with healthy HbA1c were significantly younger, less obese, and had higher HDL cholesterol. HbA1c was unaffected by the pandemic in any group. Triglycerides, total and HDL cholesterol levels fell in all groups during the pandemic. Physical activity levels in all groups were remarkably low, with most reporting no engagement in any voluntary physical activity. Engagement in physical activity or its enjoyment was lower in patients with diabetes and prediabetes than in younger, less obese patients. Major diet differences were between men and women and were present before the pandemic. Women consumed significantly more vegetables, fruit, and salad than men. The only pandemic-related change in diet was a drop in egg consumption, possibly explaining the fall in total cholesterol. CONCLUSION: Societal disruption during the COVID-19 pandemic had minimal effects on adverse health-related behaviors, cardiometabolic risk, or changes in glycemic control in a Latino community with diabetes and healthcare disparities in the Southwest US.

The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

INTRODUCTION: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. METHODS AND MATERIALS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. RESULTS: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). CONCLUSION: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

Associations of ECG Signs of Ischemic and Non-Specific Signs of Metabolic Changes in the Myocardium With Unfavorable Cardiovascular Prognosis in a 7-Year Prospective Follow-Up of Young People Under 45 Years.

AIM: To study ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium and to determine their relationship with unfavorable cardiovascular prognosis in a 7-year prospective observation of young people under 45 years of age. MATERIAL AND METHODS: A cross-sectional population survey of a random sample aged 25-44 years (n=1363) was conducted in Novosibirsk. The survey program used the standardized epidemiological Rose questionnaire. Biochemical tests were used to measure blood concentrations of total cholesterol (C), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and fasting blood plasma glucose. Systolic and diastolic BP (SBP, DBP), the presence of arterial hypertension (AH), body mass index (BMI), waist circumference (WC), and smoking status were assessed. ECG was recorded at rest in 12 standard leads followed by interpretation according to the Minnesota Code. The presence of ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium was determined. Subjects with ECG signs of ischemic changes in the myocardium were selected for long-term follow-up and additional examination by cardiologists. Then the whole cohort was monitored for 7 years, and cardiovascular events were recorded, including using data from the WHO Myocardial Infarction Registry in Novosibirsk. For statistical analysis of the results, cardiovascular events were combined into a composite endpoint. RESULTS: During 7 years, 40 people (27 men and 13 women) had an unfavorable cardiovascular prognosis. Multivariate regression analysis showed that a 7-year unfavorable cardiovascular prognosis in people younger than 45 years was associated with signs of ischemic myocardial alterations identified on the background ECG (OR 5.319, 95% CI: 1.543-18.342, p=0.008) and nonspecific ECG signs of metabolic changes in the myocardium (OR 2.978, 95% CI: 1.216-7.216, p=0.017) regardless of age, gender, the presence of arterial hypertension (AH) and type 2 diabetes mellitus (DM2). CONCLUSION: In young people under 45 years of age, not only ECG signs of ischemic changes in the myocardium, but also nonspecific ECG signs of metabolic changes in the myocardium are associated with an unfavorable cardiovascular prognosis, directly and independently on age and gender, in a long-term, 7-year period.

Sex-based association between high-density lipoprotein cholesterol and adverse outcomes after coronary artery bypass grafting.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is shown to be an independent protective factor against coronary artery diseases (CAD). Yet there are limited studies focusing on the association between HDL-C and coronary artery bypass graft (CABG) surgery outcomes. HYPOTHESIS: Low levels of HDL-C are associated with higher incidence of adverse outcomes in patients undergoing CABG. METHODS: This registry-based study included 17,772 patients who underwent elective isolated CABG between 2007 and 2017. Patients were classified into low and desirable HDL-C groups based on their serum HDL-C levels at admission and were followed for one-year post-surgery. The study population included 13,321 patients with low HDL-C and 4,451 with desirable HDL-C. proportional hazard Cox models were performed to evaluate the association between HDL-C levels and incidence of mortality as well as major adverse cardiovascular and cerebrovascular events (MACCE), while adjusting for potential confounders. Moreover, participants were stratified based on sex and the association was also investigated in each subgroup separately. RESULTS: No significant difference was found between the groups regarding incidence of both mortality and MACCE, after adjusting with Inverse Probability Weighting (IPW) [HR (95%CI): 0.84 (0.46-1.53), p-value:0.575 and HR (95% CI): 0.91 (0.56-1.50), p-value:0.733, respectively]. According to the sex-based subgroup analysis, no significant association was observed after adjustment with IPW analysis. However, as we examined the association between the interaction of HDL-C levels, sex and cardiovascular outcomes, we found a significant association (HR;1.19 (95%CI: 1.04-1.45); p = 0.030). CONCLUSION: HDL-C level was not associated with either mortality or MACCE during one year after CABG procedure. Sex-based analysis showed that in males, HDL-C is significantly more protective against these outcomes, compared to females. Further studies are necessary to elucidate the exact mechanisms mediating such association.

Association between dental scaling and metabolic syndrome and lifestyle.

PURPOSE: Periodontal disease is a risk factor for diabetes and metabolic syndrome, and non-surgical periodontal treatment has been shown to help maintain stable blood sugar in diabetic patients. Determining the level of preventive scaling in patients with metabolic syndrome will help manage the disease. The purpose of this study was to investigate the extent to which people with metabolic syndrome or bad lifestyle performed scaling and the association between preventive scaling and metabolic syndrome or lifestyle in a large population. METHODS: This study was conducted on adults aged 20 years or older from January 2014 to December 2017 in the National Health Insurance System (NHIS) database. Among 558,067 people who underwent health checkups, 555,929 people were included. A total of 543,791 people were investigated for preventive scaling. Metabolic syndrome components were abdominal obesity, lower high density lipoprotein cholesterol (HDL)-C, high triglycerides, high blood pressure and hyperglycemia. Unhealthy lifestyle score was calculated by assigning 1 point each for current smokers, drinkers, and no performing regular exercise. RESULTS: When multiple logistic regression analysis was performed after adjusting for age, sex, income, body mass index (BMI), smoking, drinking and regular exercise, the Odds ratios (OR) and 95% confidence intervals (CI) of the group with 5 metabolic syndrome components were 0.741 (0.710, 0.773) (p<0.0001). After adjustment for age, sex, income, BMI, smoking, drinking, regular exercise, diabetes, hypertension and dyslipidemia, the OR (95% CI) of the group with unhealthy lifestyle score = 3 was 0.612 (0.586, 0.640) (p<0.0001). CONCLUSIONS: The more metabolic syndrome components, and the higher unhealthy lifestyle score, the less scaling was performed.

A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk.

High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.

Diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most frequent liver disease, closely related with metabolic risk factors such as obesity, insulin resistance, dyslipidemia, diabetes mellitus, and metabolic syndrome. In this context, γ-Glutamyl transpeptidase (GGT) and high-density lipoprotein cholesterol (HDL-C) have shown correlations with steatosis severity and metabolic syndrome, respectively. This positions the GGT/HDL-C ratio as a potential diagnostic indicator for NAFLD. OBJECTIVE: To assess the diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery. METHODS: We conducted an analytical cross-sectional study, designed as a diagnostic test evaluation. A secondary database of 249 adults with obesity was analyzed. The optimal cut-off point was ascertained using three methodologies, and five adjustment models were constructed for the total population, further stratified by sex. RESULTS: The optimal cut-off point was 20.5 U/mmol and the AUC of the ratio was 0.81 (95% CI: 0.64-0.98), with sensitivity and specificity being 82.5% and 77.8%, respectively. In the overall group with an elevated GGT/HDL-C ratio, the prevalence of NAFLD increased by 14% (PR: 1.14; 95% CI: 1.04-1.33). Specifically, women displaying this altered ratio showed a 19% increased prevalence (PR: 1.19; 95% CI: 1.07-1.42) compared to those with normal values. CONCLUSIONS: The GGT/HDL-C ratio is a promising biomarker for the diagnosis of NAFLD in an adult population living with obesity.

Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model.

We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.

Impacts of pro-inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta-analysis.

Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL-6 gene) C allele was linked to higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high-density lipoprotein cholesterol (HDL-C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL-6 inhibition with ziltivekimab or canakinumab may benefit high-risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.

Asociación entre los marcadores lipídicos en la infancia/ adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática / Association between lipid markers in childhood/ adolescence and cardiovascular events in adulthood: A systematic review

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Taking appreciation to heart: appreciation at work and cardiovascular risk in male employees.

Introduction: While perceived appreciation at work has been associated with self-reported health and wellbeing, studies considering biological health markers are lacking. In this study, we investigated whether appreciation at work would relate to coronary heart disease (CHD) risk as well as the specificity of this proposed association. Methods: Our study comprised a total of 103 male participants, including apparently healthy, medication-free, non-smoking men in the normotensive to hypertensive range (n = 70) as well as medicated hypertensive and CHD patients (n = 33). CHD risk was assessed by blood pressure [mean arterial pressure (MAP)], the diabetes marker glycated hemoglobin A1c (HbA1c), blood lipids [total cholesterol (TC)/high-density lipoprotein-cholesterol (HDL-C) ratio], coagulation activity (D-dimer and fibrinogen), and inflammation [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)]. Perceived appreciation at work, as well as potentially confounding psychological factors (social support, self-esteem, and work strain due to a lack of appreciation), were measured by self-report questionnaires. Results: We found higher appreciation at work to relate to lower overall composite CHD risk (p's ≤ 0.011) and, in particular, to lower MAP (p's ≤ 0.007) and lower blood lipids (p's ≤ 0.031) in medication-free participants as well as all participants. This overall association was independent of confounding factors, including related psychological factors (p's ≤ 0.049). Discussion: Our findings indicate that appreciation at work might be an independent health-promoting resource in terms of CHD risk. Implications include that encouraging appreciation at work may help reduce the development and progression of CHD.