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Purpose of the Review: This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored., Recent Findings: The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Ample evidence supports that an individual's lifetime risk of atherosclerotic cardiovascular disease correlates to long-term, cumulative exposure to circulating cholesterol levels, beginning in childhood. Selective screening strategies based on family history fail to identify many children with hypercholesterolemia. Universal cholesterol screening in childhood is a worthwhile goal. However, cholesterol screening rates through childhood remain low., Recent Findings: Mounting evidence clarifies the barriers to cholesterol screening in children. Specific strategies to foster universal screening in childhood have been proposed., Summary: We present an overview of the present state of childhood cholesterol screening, summarizing historical and contemporary guidelines and collating evidence of low adherence to current guidelines. We contend that novel approaches to universal cholesterol screening in childhood are warranted, and we present potential opportunities for improvement. We call for new and universal pediatric cholesterol screening guidelines., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: In this review, we discuss strategies for managing dyslipidemia in pregnant women with ASCVD., Recent Findings: Cardiovascular disease (CVD) is the leading cause of mortality in women as well as the leading cause of pregnancy-related mortality in the USA. It is paramount to screen, identify, counsel, and treat women of childbearing age who have existing atherosclerotic disease to mitigate the risks of complications and mortality. Dyslipidemias, including hypercholesterolemia and hyperlipidemia, can further enhance the risk for future CVD events. Treating hypercholesterolemia during pregnancy is crucial, and this is an opportune time for cross-collaboration of subspecialties in cardiology, obstetrics, and gynecology., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Early identification and treatment of cardiovascular disease (CVD) risk factors through screening are crucial in the primary prevention of CVD and reduction in healthcare-related costs. Use of Non-Physician Healthcare-workers including Community Pharmacists has been advocated as an effective and cost-efficient model of healthcare delivery. In Nigeria the use of community pharmacists for mass screening of CVD risk factors has not been explored. Objective We sought to investigate the possibility of mass CVD risk factor screening in community pharmacies by pharmacists. Setting Lagos, Nigeria. Methods Between October and December 2018 eight hundred and eighty-nine apparently healthy participants were screened for obesity, hypertension, diabetes and hypercholesterolaemia in ten community pharmacies. Diabetes and hypercholesterolaemia were screened for using point-of-care testing modalities. A structured questionnaire was used to obtain the socio-demographic data of the participants. Main outcome measures Prevalence of overweight/obesity, hypertension, diabetes, hypercholesterolaemia, smoking and alcohol intake. Results Mean age of the subjects was 56.8 ± 21.1 years. Majority (57.4%) were females. Prevalence of smoking and alcohol intake were 4.3% and 26.7% respectively. 59.7% and 71.5% of males and females were either overweight (BMI ≥ 25 kg/m 2 ) or obese (BMI ≥ 30 kg/m 2 ) respectively. Prevalence of hypertension was 28.2% in all subjects, 30.9% in males and 26.3% in females, p < 0.001. Using BP > 130/80 mmHg prevalence of hypertension was 55.1%. Diabetes was detected in 3% of the subjects while 45.3% had hypercholesterolaemia. In total, 64.1% of the subjects were diagnosed with CVD risk factors for the first time. Conclusion Opportunistic screening for CVD risk factors is possible in community pharmacies and has the ability to detect previously undiagnosed risk factors. This community pharmacy based model could serve as a cost-effective approach to primary prevention of CVD.

Purpose: The clinical outcome after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is diverse in infertility patients with polycystic ovary syndrome (PCOS). The aim of this study was to develop a nomogram based on an association of patients' characteristics to predict the live birth rate in PCOS patients., Methods: All women in a public university hospital who attempted to conceive by IVF/ICSI for PCOS infertility from January 2014 to October 2018 were included. The nomogram was built from a training cohort of 178 consecutive patients and tested on an independent validation cohort of 81 patients. PCOS was confirmed in all participants., Results: Three variates significantly associated with live birth rate of PCOS patients were BMI, total serum cholesterol (TC) and basal FSH. This predictive model built on the basis of BMI, TC, basal FSH, type of embryo transferred and age showed good calibration and discriminatory abilities, with an area under the curve (AUC) of 0.708 (95% CI 0.632-0.785) for the training cohort. The nomogram showed satisfactory goodness-of-fit and discrimination abilities in the independent validation cohort, with an AUC of 0.686 (95% CI 0.556-0.815)., Conclusion: Our simple evidence-based nomogram presents graphically risk factors and prognostic models for IVF/ICSI outcomes in patients with PCOS, which can offer useful guidance to clinicians and patients for individual adjuvant therapy.

Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0.2). To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2-3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. This first in human study demonstrates that sirolimus therapy is associated with elevation in PCSK9 levels which is not associated with sirolimus-induced hypercholesterolemia.

Background: Lipid metabolism disorder is recognized to be associated with obstructive sleep apnea (OSA); however, inconsistent results have been reported. The aim of this study was to evaluate the association between lipid profile and OSA with adjustments for multiple confounding factors., Methods: In total, 2983 subjects were recruited from the Shanghai Sleep Health Study (SSHS) during 2007-2013. Data for overnight polysomnography (PSG) parameters, serum lipids, fasting blood glucose, insulin levels, and anthropometric measurements were collected. Multivariable logistic regression analyses were used to determine the correlation between lipid profile and OSA with adjustments for confounders including lipids, age, gender, Epworth sleepiness scale, body mass index, waist/hip ratio, glucose, insulin resistance, hypertension, and smoking., Results: The prevalence of hyper total cholesterol (TC), hyper triglycerides, hypo high-density lipoprotein cholesterol, hyper low-density lipoprotein cholesterol (LDL-C), hyper apolipoprotein (apo) A-I, and hyper apoB differed significantly between the non-OSA and OSA patients. Without considering the interaction across different lipids, TC, LDL-C, and apoB were independently associated with OSA in primary multivariable logistic regression analyses; the odds ratios (ORs) and 95 % confidence intervals (CIs) were 1.262 (1.109-1.438), 1.432 (1.233-1.664), and 5.582 (2.643-11.787), respectively. However, only LDL-C (OR = 1.430, 95 % CI = 1.221-1.675) was found to be an independent risk factor for OSA in further multivariable logistic regression analyses., Conclusions: We demonstrated that patients with OSA had a higher percentage of dyslipidemia than subjects without OSA. Of the various components in serum lipid, only LDL-C was independently associated with OSA.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

Glycemic effects of statins have recently become a topic of heated debate. On closer inspection, however, the prevailing opinion regarding this issue may prove to be unsubstantiated. We suggest that the harmful effect of statin-induced diabetes is likely overestimated, and the consequences of the glycemic effects of statins may, theoretically, apply to a greater number of patients beyond just those with statin-induced diabetes. Most notably, though, careful consideration of the issue suggests, albeit surprisingly, that the clinical implications of the glycemic effects of statins may actually be rather limited.

Sitosterolemia is a rare autosomal recessively inherited disease caused by mutations affecting ABCG5 or ABCG8, which are located on human chromosome band 2p21. Around 100 cases have been reported in the literature. Sitosterolemic patients typically exhibit a 30-fold to 100-fold increase in plasma concentrations of plant sterols. The clinical manifestations include xanthomas, premature atherosclerosis, hemolytic anemia, and macrothrombocytopenia. It is noteworthy that abnormal hematological parameters may be the only clinical feature of sitosterolemic patients, suggesting that sitosterolemia may be more frequent than previously thought. Severe accumulation of plant sterols in mouse models of sitosterolemia induced complex cardiac lesions, anemia, and macrothrombocytopenia, disrupted adrenal and liver cholesterol homeostasis, and caused infertility and hypertriglyceridemia. It remains unclear whether all disease traits are present in sitosterolemic patients. The drug ezetimibe appears to be effective in reducing plasma plant sterol levels, promotes xanthoma regression, and improves the cardiovascular and hematological signs in sitosterolemic patients.

Background: While statin drugs are recommended for secondary prevention of coronary heart disease (CHD), there is no medical consensus on whether or not a statin should be added to lifestyle change efforts for primary prevention of CHD. Previous research suggests that exposure to direct-to-consumer advertising (DTCA) increases drug demand among those at comparatively low risk. Research has yet to examine whether individual-level DTCA exposure may influence statin use among men and women at high, moderate, or low risk for future cardiac events., Objective: To determine the relationship between estimated exposure to DTCA for statin drugs and two clinical variables: diagnosis with high cholesterol and statin use., Design: We used logistic regression to analyze repeated cross-sectional surveys of the United States population, merged with data on the frequency of DTCA appearances on national, cable, and local television, between 2001 and 2007., Participants: American adults (n=106,685) aged 18 and older., Main Measures: Levels of exposure to statin DTCA, based on ad appearances and TV viewing patterns; self-reports of whether or not a respondent has been diagnosed with high cholesterol, and whether or not a respondent took a statin in the past year., Key Results: Adjusting for potential confounders, we estimate that exposure to statin ads increased the odds of being diagnosed with high cholesterol by 16 to 20 %, and increased statin use by 16 to 22 %, among both men and women (p<0.05). These associations were driven almost exclusively by men and women at low risk for future cardiac events. There was also evidence of a negative association between DTCA exposure and statin use among high-risk women (p<0.05) CONCLUSIONS: This study provides new evidence that DTCA may promote over-diagnosis of high cholesterol and over-treatment for populations where risks of statin use may outweigh potential benefits.

Background: Obstructive sleep apnea (OSA) is a common and underrecognized disorder affecting at least 2% and 4% of women and men, respectively. Chronic kidney disease (CKD), on the other hand, affects around 13% of US adults. Both of these conditions share some risk factors such as age, obesity, and smoking and are associated with increased cardiovascular morbidity and mortality. By itself OSA may play a role in the development of arterial hypertension, metabolic syndrome, type 2 diabetes mellitus, and dyslipidemia with potential impact on CKD development and/or progression. But the data regarding OSA and CKD are relatively scant., Discussion: Moreover, several studies had shown possible harmful effects on kidney function independent from conventional risk factors. CKD is associated with excessive fluid volume, with potential shift during recumbency towards the neck area with increased upper airway resistance. Thus, OSA and CKD may be the results of each other and when present together may impose much greater cardiovascular risk than either disease alone.

Purpose: The relationship between obstructive sleep apnea (OSA) syndrome and metabolic syndrome is far from conclusion for obesity as a confounding factor. The aim of the present study was to investigate the association between OSA and some components of metabolic abnormality in nonobese patients., Methods: We consecutively recruited nonobese subjects who underwent polysomnography and analyzed some components of metabolic abnormality in subjects with and without OSA. Multiple linear regression was used to evaluate the independent risk factor of some components of metabolic abnormality., Results: A total of 154 subjects were enrolled and were divided to control group (45 subjects) and OSA group (113 subjects). Body mass index was no different between groups. Systolic blood pressure, triglycerides, and insulin concentration were significantly higher among OSA group compared with control group (p = 0.000, 0.043, and 0.006, respectively), and the prevalences of dyslipidemia, hypertension, and at least two of the metabolic abnormalities were significantly greater in OSA group (p = 0.003, 0.031, and 0.000, respectively). After adjusting for confounding factors, lowest O(2) saturation was the major contributing factor for elevated systolic blood pressure (p = 0.001), and independent associations were found between apnea-hypopnea index and the following parameters of metabolic abnormality: triglycerides and homeostasis model assessment of insulin resistance (all p = 0.000)., Conclusions: Our finding was consistent with previous studies that OSA was independently associated with dyslipidemia, hypertension, and at least two of metabolic abnormalities in nonobese patients.

Background: Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated., Objective: To analyze the management of hypercholesterolemia in a non-experimental setting and to estimate the factors associated with poor adherence to treatment., Methods: A longitudinal study was performed using clinical and demographic data recorded in the General Practitioners' database. The sample included all patients, aged 30 years or over, with total blood cholesterol measured between 1 January and 31 December 2000. Utilization of LLDs was defined as the standardized daily dose of the drugs purchased during the 12 months preceding the cholesterol measurement., Results: The study included 4764 patients (mean age 59.4+/-14.1 years, 40.7% males). Of the subjects with a total cholesterol higher than a 6.5 mmol/l, approximately 17% were treated with LLDs. About 39% of the patients with previous atherosclerotic diseases were taking statins. Analysis of patients taking LLDs showed that 40.6% of subjects took less than half of the defined daily dose. Factors associated with poor adherence to treatment were: absence of previous atherosclerotic diseases, absence of concomitant diseases, and smoking. A total cholesterol of less than 5 mmol/l was achieved in 19.9% of patients., Conclusions: Analyzing the data contained in the general medicine database made it possible to evaluate the use of LLDs in clinical practice and to establish the need to pay greater attention to achieving the objective set by the treatment.

Human breath contains hundreds of trace volatile organic compounds. These volatile substances may be generated in the body or may be absorbed as contaminants from the environment. Some of the endogenous substances are characteristic markers of pathophysiological processes and clinicians are already using breath testing of such substances as an additional non-invasive diagnostic tool for certain diseases. Isoprene, another volatile compound, is formed endogenously in humans, and while the biochemical pathways of biosynthesis and exact origins of isoprene found in human breath have not been elucidated in sufficient depth, its measurement in exhaled breath has been suggested as a non-invasive indicator with diagnostic potential. This test has not yet reached the level of routine clinical methods and is still under development. Breath isoprene levels have been reported to be altered in a number of clinical conditions; however, the physiological meaning of these changes has not been established. Various lines of supportive evidence suggest that isoprene is related to cholesterol biosynthesis. Therefore, breath isoprene measurements could potentially be used for mass screening for lipid disorders and could, at minimum, serve as an additional parameter to complement invasive tests for monitoring the efficacy of lipid-lowering therapy, pharmacological and dietary or lifestyle. As a potentially useful biomarker of mevalonate synthesis in humans, it may have non-invasive applications, not only in metabolic disorders, but possibly also in cancer screening. In the present work, we aim to give a concise overview of breath isoprene, its measurement techniques, problems concerning its physiological meaning, and potential applications as a non-invasive biomarker in modern medicine.

The purpose of this cross-sectional survey was to estimate the prevalence of lipodystrophy (LD) and metabolic abnormalities in Slovenian patients with HIV infection. All patients receiving highly active antiretroviral therapy (HAART) for more than six months (treated group) and all known antiretroviral-naive patients (control group) were consecutively evaluated between October and December 2003. Eighty-one treated patients (81% male, 19% female), and 18 controls (83% male, 17% female) were included in the study. In the treated group, the duration of HAART at the time of evaluation was 3.7 +/- 2.3 years. Twenty-nine treated patients (36%) had at least one sign of LD: isolated peripheral atrophy was present in nine (31%), isolated fat accumulation in four (14%) and a mixed syndrome in 16 (55%). Patients with evidence of LD were older than those without LD and had a higher prevalence of AIDS and a longer duration of HAART, but there were no differences in HIV transmission categories, plasma RNA level, CD4+ count, HAART regimens or BMI. Insulin resistance was observed in 31 treated patients (38%), of whom 22 (27%) had impaired glucose tolerance and six (7%) had diabetes mellitus. Dyslipidemia was the predominant metabolic abnormality in the treated group, observed in 58 patients (72%). Levels of total cholesterol were increased in 43 patients (53%), and hypertriglyceridemia was noted in 40 (49%). The duration of HAART in patients with metabolic syndrome was longer than in patients without the syndrome. Lipid- and glucose-related abnormalities were more frequent in patients with LD than in those without. A total of 60 treated patients (74%) had at least one sign of LD and/ or one metabolic alteration at the time of evaluation. In the control group, none of the patients showed evidence of LD, and metabolic abnormalities were less common than in the treated group: six patients (33%) had one or more metabolic abnormalities. HIV-related LD syndrome includes a variety of clinical and biological manifestations, which can be included in a case definition. The metabolic effects of HAART could lead to an increase in cardiovascular disease. The patient's metabolic parameters should be evaluated before starting treatment, and appropriate management of LD and glucose- or lipid-related metabolic changes is essential.

Objective: To evaluate racial and ethnic disparity in blood pressure and cholesterol measurement and to analyze factors associated with any observed disparity., Design: Cross-sectional analysis of the household component of the 1996 Medical Expenditure Panel Survey., Participants: Representative sample of the U.S. non-institutionalized population age 21 or older., Measurements: Prevalence of self-reported blood pressure measurement within 2 years and cholesterol measurement within 5 years were calculated by race/ethnicity. Logistic regression was used to adjust for health insurance status, having a usual source of care, health status, and socioeconomic and demographic factors. Odds ratios and 95% confidence intervals (95% CIs) from the logistic regression were converted to prevalence ratios to estimate relative risk (RR)., Main Results: Mexican Americans compared to non-Hispanic whites were less likely to have a blood pressure measurement (RR, 0.85; 95% CI, 0.81 to 0.89) or a cholesterol measurement (RR, 0.72; 95% CI, 0.65 to 0.78). Non-Hispanic blacks had blood pressure and cholesterol measurements similar to non-Hispanic whites. In a multivariate analysis, Mexican Americans had similar blood pressure measurements (RR, 0.97; 95% CI, 0.94 to 1.00) and cholesterol measurements (RR, 1.04; 95% CI, 0.99 to 1.08). The factors associated with the largest disparity were lack of health insurance, not having a usual source of care, and low education., Conclusions: No disparity was found between non-Hispanic blacks and non-Hispanic whites in undergoing blood pressure and cholesterol measurement. Disparities in cardiovascular preventive services for Mexican Americans were associated with lack of health insurance and a usual source of care, but other demographic and socioeconomic factors were also important.

This review concerns the clinical impact of low-density lipoprotein (LDL) apheresis for patients with refractory hypercholesterolemia. We examine and provide examples of investigations that have demonstrated the clinical benefits of LDL apheresis. In addition to benefits derived from the stabilization or regression of arterial lesions, we highlight other possible mechanisms related to clinical improvement. We also discuss the potential advantages of lipid apheresis for the treatment of patient populations other than those characterized by severe hypercholesterolemia and premature coronary heart disease.