Development Of Atherosclerotic Cardiovascular Disease Research Articles

Abstract 4134572: Assessing Sex Differences in the Relationship Between Social Isolation and Incident Atherosclerotic Cardiovascular Disease and Death Using Data from the U.S. Health and Retirement Study

Background: Inadequate social connection has been associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and mortality. There are insufficient and conflicting data on whether sex differences play a role in this relationship. Therefore, we sought to further examine the relationship between sex, social isolation, and these subsequent events. Methods: We analyzed Health and Retirement Study (HRS) and RAND data collected biennially from 8,987 individuals enrolled from 2004-2020 who completed at least 1 Leave Behind Questionnaire (LBQ). Social isolation was determined from LBQ data using a previously validated 6-item scale where scores of 3 or greater indicated social isolation. Development of ASCVD was classified as new self-reported myocardial infarction or stroke at any follow-up assessment. Mortality was determined with RAND longitudinal data, which was available for all individuals. We examined the incidence of ASCVD in socially isolated and not socially isolated individuals using a cumulative incidence function accounting for the competing risk of death. Results: Mean age at baseline LBQ survey was 55.7 years and 43% of the sample were male. In the sample, 23% identified as Black, 63% identified as White, and 13% identified as Other. Social isolation was present in 1,653 (18%) individuals at their baseline survey. ASCVD developed in 484 (5%) participants, and 593 (7%) participants died over the study’s follow-up period. Cumulative incidence analysis showed no significant difference in ASCVD incidence between socially isolated and non-socially isolated groups for either sex (male p-value: 0.15; female: 0.09) (Figure). However, the incidence of death was significantly increased for both socially isolated sexes (male p-value: <0.001; female: <0.001). Conclusion: While socially isolated participants were not at significantly increased risk of incident ASCVD, they were at significantly increased risk of mortality, irrespective of sex. This highlights the need for continued public health initiatives that foster social connection to enhance the well-being of the general population. The study is limited by reliance on self-report for ASCVD, which may underestimate disease incidence.

Abstract 4131815: The Prevalence of Normal Coronary Arteries as Determined by a Coronary Artery Calcium Score of Zero Amongst Subjects with Diabetes Mellitus

Background: The CDC reports that in 2021, 11.6% of the American population had diabetes mellitus (DM). Past literature has shown diabetes to be a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Research Question/Goal: Using data obtained through Computed Tomography Angiography (CTA), we aim to distinguish the risk factors associated with a coronary artery calcium (CAC) score of zero in subjects with DM and to identify the prevalence of non-calcified plaque in individuals with this score. Methods: We performed a retrospective study of patients with DM, who underwent CAC and CTA screenings from October 2004 to January 2024 at our center in Torrance, California to examine CTA outcomes in those with CAC Score of zero and greater than zero. Results: Among the cohort of 2,763 subjects with DM, the average age was 63.8±12.2 years, 62% male. Within this cohort, 465 (17%) subjects had a CAC Score of zero compared to 2,298 subjects with a CAC Score greater than zero with a median score of 428 (Interquartile range (IQR) 91-1267). DM subjects with CAC Score of zero were significantly younger (53.0±13.9 versus 66.0±10.6: p<0.001), were more likely to be female and had significantly lower rates of hypertension (57% versus 76%: p<0.001), and hyperlipidemia (63% versus 76%: p<0.001). In DM subjects with CAC Score of zero, 133 (29%) had a total plaque severity score of 1 or greater (median 1, IQR 1-2) while 332 (71%) had normal coronaries on CTA. Conclusions: A significant percentage of subjects with DM were determined to have a CAC score of zero. Subjects with normal coronary arteries were more likely to be younger, female, and/or absent of other chronic diseases such as hypertension and hyperlipidemia. Although age and sex are nonmodifiable risk factors of ASCVD, limiting the comorbid conditions associated with DM may be beneficial in preventing ASCVD in individuals with diabetes.

Advanced biologic therapies are associated with fewer adverse cardiovascular events in patients with inflammatory bowel diseases

Abstract Background Chronic inflammation is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD) and associated events. Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions, and meta-analyses of cohort studies demonstrate an increased risk of ASCVD events in IBD patients. Advanced biologic therapies (ABT) targeting the immune system revolutionized treatment of IBD patients but the impact of these therapies on ASCVD events is not known. Purpose To investigate the impact of ABT on ASVCD events in IBD patients. Methods A retrospective cohort study was performed using the TriNetX Diamond Network, a multi-institutional database providing real-time access to de-identified electronic health records, with data updated on 02/14/2024. ABT were defined as one or more the following: infliximab, adalimumab, golimumab, certolizumab pegol, ustekinumab, risankizumab, vedolizumab, or natalizumab. ASCVD events were based on ICD codes for ischemic heart, cerebrovascular, and peripheral vascular diseases. Individuals >40 years with IBD were included. ASCVD events in (1) patients on ABT and (2) patients not on ABT (NABT) were compared. Propensity score matching was performed on sex, aspirin use, and the following ASCVD risk factors: age, hypertension, hyperlipidemia, tobacco use, and type 2 diabetes mellitus. Results This study includes 72,650 individuals in each of the two matched cohorts. There were no differences in baseline characteristics between the two propensity-score matched cohorts (Table). The probabilities of experiencing any ASCVD event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (8.3% vs. 12.4%, OR 0.64; 13% vs. 18.6%, OR 0.66; and 15% vs. 21.2%, OR 0.65; respectively, all p<0.01). Similarly, the probability of experiencing an ischemic heart disease event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (5.2% vs. 7.9%, OR 0.64; 8% vs. 11.7%, OR 0.66; and 9.2% vs. 13.4% OR 0.66; respectively, all p<0.01). The probability of cerebrovascular disease events at one, three, and five years in the ABT group were all significantly lower than in the NABT group (2% vs. 3.3%, OR 0.59; 3.5% vs. 5.7%, OR 0.59; and 4.2% vs. 6.8% OR 0.60; respectively, all p<0.01) and the probability of a peripheral artery disease event at one, three, and five years in the ABT group were also all significantly lower than in the NABT group event (2.8% vs. 4.5%, OR 0.62; 5.1% vs. 7.6%, OR 0.65; and 6.2% vs. 9.3% OR 0.65; respectively, all p<0.01). Conclusions ABT are associated with significantly fewer ASCVD events in the IBD patient population. Future studies examining the differential benefit of drug subclasses on ASCVD outcomes and mechanisms responsible for the ABT benefit, as well as prospective study designs have the potential to identify new therapeutic targets in IBD patients and with applicability beyond IBD patients.Table

Electronegative ApoCIII-Rich HDL promotes cellular damage and vascular aging

Abstract Background Experimental studies attributing HDL a cardioprotective effect are challenged by well-designed randomized controlled trials showing largely neutral results, which might be related to more recent observations that certain HDL particles exert detrimental effects. This study explores the effects of electronegative HDL on cellular damage and vascular aging. Using anion-exchange chromatography, HDL was divided into five subclasses (H1 to H5) based on increasing electronegativity. Compared to the health-promoting H1, the most electronegative subclass, H5 contains significantly higher levels of ApoCIII and triglycerides (TG). Purpose Herein, we aim to explore the cellular and molecular mechanisms underpinning H5-induced pathology in human umbilical vein vascular endothelial cells (HUVECs), which may accelerate vascular aging preceding the development of atherosclerotic cardiovascular disease (ASCVD). Methods H1 and H5 were isolated from patients with metabolic syndrome (MetS). To gauge the impact of H5 on vascular integrity, HUVECs were treated with solvent, H1, or H5 at concentrations of 25, 50, or 100 µg/mL. Cell viability and apoptosis were evaluated using the MTT assay and PI/Calcein fluorescent staining, respectively. Immunofluorescence staining and immunoblotting, focusing on 8-oxodG, P53, and β-gal, proxies of DNA damage and cellular senescence, were performed. Senescence-associated secretory phenotype (SASP) analysis was done to elucidate the senescent mechanism. By harnessing Mitosox imaging reactive oxygen species (ROS) synthesis was monitored. Finally, unbiased lipid- and transcriptomics were used to identify lipid components potentially involved in H5 signaling. Results As compared to controls, MetS patients exhibited more electronegative HDL particles, as indicated by increased H5 (1.604±0.410% vs 4.598±4.712%, P=0.0016). Remarkable elevations were noted in individuals with severe clinical complications, as shown in the representative patient with left ventricular hypertrophy, chronic coronary syndrome, and heart failure (Fig. 1). In HUVECs, H5 but not H1 reduced cell viability and increased apoptosis in a concentration-dependent manner. In parallel, H5 but not H1 induced cell aging, ROS production, and DNA damage, with SASP cytokines including IL-1β, IL-6, CCL2, TNF-α, and γH2AX (Fig. 1). Notably, compared to H1, H5 exhibited high contents of various TG species, impairing H5’s anti-inflammatory and antioxidant capacities, along with reductions in several phosphatidylcholines that may constitute essential cell membrane structural components, as evidenced by lipidomic studies (Fig. 2). Conclusion H5, the most electronegative and dysfunctional HDL subfraction, is capable of inducing DNA damage, oxidative stress, and senescence in vascular ECs. Its notable elevation in patients with MetS highlights a previously unrecognized etiology, shedding light on how electronegative HDL may contribute to and expedite ASCVD.Fig 1Fig 2

Lipoprotein(a) levels in patients with cryptogenic stroke and persistent foramen ovale

Abstract Background Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, it is not known whether high Lp(a) is associated with cryptogenic stroke. Methods We included 478 patients with cryptogenic stroke that underwent closure of a persistent foramen ovale and had Lp(a) measurement available. These patients were matched according to age and gender in a 1:3 ratio to 1434 controls. Results Mean age of patients was 49.9 +/-12.9 years and 275 patients (57.4%) were male. Median Lp(a) levels were significantly higher in cases (26 IQR 13 – 87 nmol/L) as compared to controls (16 IQR 2 – 61 nmol/L; p<0.00001). Lp(a) levels > 200 nmol/L were significantly more frequent in patients with cryptogenic stroke as compared to controls (10.0 % vs. 7.0 %; p<0.05). The odds-ratio for an increase of Lp(a) by 50nmol/L was 1.09 (95% CI 1.03 – 1.15) independent of age and gender. Conclusion Patients with cryptogenic stroke and persistent foramen ovale showed significantly higher plasma levels of Lp(a) and an increase of Lp(a) was associated with a significant increased risk for cryptogenic stroke. Whether high Lp(a) increases risk for deep vein thrombosis leading to embolization or for arterial thrombosis has to be elucidated in further studies.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

Association between colchicine use and adverse cardiovascular events in patients with gout: a nationwide nested case-control study.

The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout. This nested case-control study utilized the nation-wide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities, and medications. The main exposure was colchicine use, assessed by 1) the cumulative defined daily doses (cDDDs) and 2) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined, separately. Overall, 9,346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% confidence interval) were were 1.09 (1.04-1.15) for <90 cDDDs, 1.20 (1.07-1.33) for 80-179 cDDDs, and 1.21 (1.09-1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality, respectively. Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.

The Effect of Retinoids in Vascular Smooth Muscle Cells: From Phenotyping Switching to Proliferation and Migration.

Atherosclerosis, a term derived from the Greek "athero" (atheroma) and "sclerosis" (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice.

Prevalence Of Metabolic Syndrome in Peri and Postmenopausal Women Aged 40- 65 Years in a Tertiary Care Centre

Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors—that appear to directly promote the development of atherosclerotic cardio-vascular disease (ASCVD). Menopausal transition with its incidental hormonal changes is considered to contribute to the development of MetS. This was a hospital based cross sectional descriptive study conducted in the Obstetrics and Gynaecology department of Nepal Medical College Teaching Hospital, Attarkhel, Gokarneshwor-8, Kathmandu, from the 1st of September 2023 till the 29th of February 2024 after clearance from the IRC (Ref. No: 56-080/081). Convenience sampling was used among women who fulfilled the inclusion criteria. The aim of the study was to determine the prevalence of MetS among the peri and postmenopausal women and to determine which component of the diagnostic criteria of MetS was more strongly associated with MetS in our population. Women were evaluated to have MetS using both the International Diabetes Federation (IDF) and the National Cholesterol Education Program- Adult Treatment Panel III (NCEP-ATPIII criteria). The prevalence of MetS by the IDF criteria was 54% among the perimenopausal women and 61% among the postmenopausal women. Similarly, the prevalence of MetS according to NCEP-ATPIII was 53.5% among the perimenopausal and 65% among the postmenopausal women. All the MetS diagnostic markers showed a strong correlation with MetS (p&lt;0.001). The prevalence of MetS is high in our population by both the IDF and NCEP-ATP III criteria, being higher in the postmenopausal population, though not statistically significant.

Long-Term Evaluation of Lipid Profile Changes in Olympic Athletes.

Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115mg/dl, high-density lipoprotein (HDL) <40mg/dl for males, or HDL <50mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150mg/dl. At the follow-up, a variation of ±40mg/dl for LDL, ±6mg/dl for HDL, and ±50mg/dl for triglycerides was considered relevant. Athletes with follow-up <10months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6months. Mean age was 27.2 ± 4.8years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease.

The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity. The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity. The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity. The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

The prognostic role of remnant cholesterol in Asian menopausal women received percutaneous coronary intervention with acute coronary syndrome

BackgroundRemnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain.MethodsRC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events.Results1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events.ConclusionAmong menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.

Atherosclerotic cardiovascular disease following a diagnosis of idiopathic inflammatory myopathy: analysis from a retrospective cohort in the TriNetX registry.

Idiopathic inflammatory myopathies (IIM) confer an increased risk of morbidity from atherosclerotic cardiovascular disease (ASCVD). While ASCVD risk has been studied in other countries, these results may not be applicable to patients with dermatomyositis (DM) and polymyositis (PM) in the United States. This retrospective analysis of a cohort of patients identified by ICD code from TriNetX investigated the incidence of ASCVD after International Classification of Disease (ICD) codes of DM, PM, dermatopolymyositis (DPM) or juvenile dermatomyositis (JDM). Patients were identified by entry of two ICD codes separated by at least 6months, according to their first diagnosis code; ASCVD was defined as first ICD code for myocardial infarction, ischemic stroke, transient ischemic attack, or peripheral arterial disease. Cox proportional hazards regression modeled time from first IIM ICD code to ASCVD event. A total of 35,554 patients were identified with the mean age at first IIM code of 54 and 26.1% were male. The most common comorbidity for all groups except JDM was hyperlipidemia (39.9%) though 79.2% of patients were on no cholesterol lowering medication. ASCVD occurred in 30.4% of patients with PM, 24.3% of patients with DM and 0.9% of patients with JDM. Patients with PM had a median time to event of 9.7years (95% Confidence interval (CI) 9.1, 10.7) and 14.3years (95% CI 12.6, 14.8) for DM. This study demonstrates that ASCVD is a comorbidity occurring after a median of 12.5years (95% CI 11.9, 13.6) in patients with IIM. ASCVD appears to be a long-term complication for IIM patients occurring in nearly a quarter of US patients without prior ASCVD with at least two ICD codes for IIM, with a median time to event of 12.5years. There appears to be a practice gap in the recognition and treatment of hyperlipidemia in these patients. Key Points • Hyperlipidemia was a common comorbidity identified in patients with IIM though most patients were not on cholesterol lowering medication. • Development of ASCVD appears to be a long-term complication for patients with IIM in the United States.

The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.

Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.

HDL cholesterol efflux capacity and cholesterol loading capacity in long-term fasting: Evidence from a prospective, single-arm interventional study in healthy individuals

Background and aimsLong-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC). MethodsForty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction. ResultsLF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels. ConclusionsLF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health. Trial registration numberNCT05031598.

Frequency of lipoprotein(a) testing and its levels in Pakistani population.

Lipoprotein(a) [Lp(a)] is a highly atherogenic particle identified as an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This study aimed to investigate the frequency of Lp(a) testing and the incidence of elevated Lp(a) levels in the Pakistani population. For this observational study, Lp(a) and lipid profile data from five years (June 2015 to October 2020) were acquired from the electronic patient records of a diagnostic laboratory with a countrywide network. The association of age and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL, and triglyceride (TG) levels with two thresholds for Lp(a), that is, <30 mg/dL and ≥30 mg/dL, was calculated using the Kruskal-Wallis test, while the association between Lp(a) levels and lipid variables was calculated using Spearman correlation. For five years, 1060 tests were conducted, averaging 212 tests per year. Of these, 37.2% showed Lp(a) levels above 30 mg/dL. No significant differences were observed in the results between males and females. However, younger individuals displayed significantly higher Lp(a) levels. Additionally, there was only a weak correlation between the Lp(a) levels and other lipid variables. Despite being recognized as a risk factor for ASCVD in the Pakistani population, only a small proportion of the large population underwent Lp(a) testing. Moreover, a significant proportion of the population exceeded this threshold.

DEFICIENCY OF VITAMIN D IN PATIENT WITH PRIMARY HYPOTHYROIDISM AND AS RELATED RISK FACTOR FOR CARDIOVASCULAR DISEASES

Hypothyroidism is believed to be associated with dyslipidemia and is considered a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD). Vitamin D, due to its steroid hormone action, retains cell function and controls the metabolism of lipids. Therefore, the present study was carried out to show the association of the risk factors of ASCVD. Cardiovascular disease (CVD) is caused by both clinical and subclinical hypothyroidism by disrupting healthy endothelial function by various mechanisms such as inflam- mation, triggering lipid disorders and oxidative stress. In the present study, a strong correlation was observed between increasing TSH and the parameters of lipid profile Hypothyroidism and hypovitaminosis D are known as inde-pendent risk factors for the development of cardiovascular diseases. Hypothyroidism and hypovitaminosis D are associated and correlated with total cholesterol, triglycerides, and low-density lipoprotein in Saudi patients. It is also recom- mended that vitamin D deficiency be checked in hypothyroid patients and that appropriate supplementation may be given if needed. Furthermore, for early detection and/or prediction of cardiovascular disease, screening of thyroid hormone and vitamin D levels should be undertaken at an early stage.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study

BackgroundDiabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes.MethodsThe Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed.ResultsThis study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all).ConclusionsIn this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Gender-related and PUFA-related differences in lipoprotein-associated phospholipase A2 levels in patients with type 2 diabetes and atherosclerotic cardiovascular disease.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play an important role in the development of atherosclerotic cardiovascular disease (ASCVD). Increased plasma levels of Lp-PLA2 may predict future cardiovascular (CV) events in type 2 diabetes (T2D). The potential beneficial effects of polyunsaturated fatty acids (PUFA) on ASCVD have been widely investigated. However, the impact of different PUFA concentrations on Lp-PLA2 remains uncertain. We sought to determine the intergender differences in a population of patients with both T2D and ASCVD regarding Lp-PLA2 mass and the association between Lp-PLA2 mass and plasma levels of PUFA. In this cross-sectional study, we measured the Lp-PLA2 mass, PUFA concentrations and inflammatory markers in 74 patients (49 males and 25 females) with T2D and ASCVD. In this very high-risk population, males had, on average, 33.6% higher levels of Lp-PLA2 than females. The Lp-PLA2 mass was positively associated with interleukin 6 (IL-6) (r = 0.27, p = 0.019), creatinine (r = 0.29, p = 0.03) and triglyceride levels (r = 0.41, p = 0.002). Additionally, male gender and higher levels of triglycerides, leptin, oxidized low-density lipoprotein (oxLDL), and intercellular adhesion molecule 1 (ICAM-1) were independent predictors for an increased Lp-PLA2. Moreover, arachidonic acid (AA) negatively correlated with Lp-PLA2 (r = -0.26, p = 0.024), which was especially apparent in the female subgroup. In the population of patients with ASCVD and T2D, males present with higher plasma levels of Lp-PLA2 than females. Additionally, higher plasma levels of AA were associated with lower Lp-PLA2 levels. Our findings support the utilization of Lp-PLA2 as a novel biomarker in ASCVD risk assessment in a very high CV risk population.

Diagnosis and treatment of dyslipidemia in children and adolescents

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide, including in South Korea. Dyslipidemia is an independent risk factor for the development of atherosclerotic cardiovascular diseases. There is strong evidence that atherosclerosis begins early in life and that elevated lipid levels in childhood predict elevated lipid levels into adulthood.Current Concepts: A universal approach for cholesterol screening in all children is recommended. Lipid profiles should be studied for all children aged 9 to 11 years and then for those aged 17 to 21 years, as cholesterol levels may vary after puberty. The non-fasting lipid profile can be as useful in detecting severe genetic dyslipidemias as the fasting lipid profile and thus can be used as a first-line screening in children. The initial treatment for dyslipidemia in a child always begins with a 6-month trial of lifestyle modifications, such as improvements in dietary and physical activity patterns. Statins are as effective in children as in adults and can lower low-density lipoprotein cholesterol levels by up to 50%. Therefore, they are considered first-line therapy for children who meet the criteria for pharmacological therapy.Discussion and Conclusion: Statins and non-statin lipid-lowering agents can lower cholesterol levels with minimal adverse effects in children and adolescents with hypercholesterolemia. However, limited data is currently available on the long-term safety and efficacy of lipid-lowering agents in the pediatric population. Furthermore, non-statin lipid-lowering agents are used far less frequently in children. Therefore, further long-term safety and efficacy studies on lipid-lowering agents in pediatric populations and clinical trials with non-statin lipid-lowering agents are required.