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• Lp(a) level should be measured at least once in all adults. • Lp(a) levels represent a continuum of risk, not a risk threshold at a dichotomous cutpoint. • Risk classification by Lp(a) level ranges from low (<75 nmol/L) to high (≥125 nmol/L). • Lp(a) risk categories apply across races and ethnicities. • High Lp(a) levels warrant early and more-intensive risk factor management. Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30–50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention. [Display omitted] [ABSTRACT FROM AUTHOR]

This CME activity was supported by an educational grant from Regeneron Pharmaceuticals, Inc. Despite the clear benefit of early treatment of homozygous familial hypercholesterolemia (HoFH) in reducing the risk of progressive atherosclerotic cardiovascular disease (ASCVD), many patients remain undiagnosed until advanced ASCVD is present. Diagnostic delays may relate to low screening rates found among at-risk children <9 years old. To study the impact of an online CME program to enhance health care providers' (HCPs') competence in diagnosing and managing HoFH and to overcome barriers to screening for at-risk children. A 60-minute CME activity was launched live online on 8/2/23 and is available on-demand for 1 year. Knowledge, attitude, and practice-pattern questions were administered before and immediately after the activity (pre vs post). Chi-square tests compared paired responses (P<0.05; pre/post). As of 1/2/24, 260 HCPs engaged in the program (30% cardiologists, 6% endocrinologists, 29% PCPs; 17% specialize in lipid management or are lipidologists). Nearly 60% of HCPs reported managing patients with very high lipid levels (>400 mg/dL) and the average number of patients with very high lipid levels managed by these participants is 17 per year (approximately 5 of whom are <9 years of age). HCPs' knowledge of the diagnostic criteria for HoFH (30% vs 58%), mechanism of action of ANGPTL3 inhibitors (22% vs 43%), and treatment intensification strategies (48% vs 62%) increased significantly during the CME activity. Before the activity, approximately 20% of respondents did not measure lipid levels in children <9 years old, 20% only measured in children with a parent diagnosed with familial hypercholesterolemia (FH) or with a family history of CVD, and 24% only measured in children with HoFH symptoms. After the activity, HCPs estimated that 60% of their patients with very high lipid levels (>400 mg/dL) may have undiagnosed HoFH. The proportion of HCPs who strongly agreed with the American Academy of Pediatrics' recommendation for lipid screening for children with a genetic risk of FH or ASCVD as early as age 2 years increased from 14% to 37%. CME can break down barriers to lipid screening in children at risk for HoFH by enhancing HCPs' knowledge of HoFH diagnosis and risk factors. While the activity enhanced knowledge about the evolving treatment landscape, future education on guidelines and treatment intensification can address remaining gaps in the adoption of best practices and novel agents for HoFH. [ABSTRACT FROM AUTHOR]

• Very low albumin levels are associated with hypercholesterolemia. • Congenital analbuminemia (CAA) is a rare cause of hyperlipidemia. • CAA is established by genetic testing of ALB. • Early diagnosis may enable earlier lipid therapy to prevent coronary artery disease. • This is the first report of PCSK9 inhibitor for hyperlipidemia associated with CAA. A 20-year-old male presented with severe elevation in low-density lipoprotein cholesterol (LDL-C). Initial genetic testing for familial hypercholesterolemia was negative. Patient also had low albumin, and further genetic testing showed homozygous variants in the ALB gene, suggesting congenital analbuminemia (CAA) causing severe hyperlipidemia. CAA is an autosomal recessive disorder with incidence of about 1:1,000,000. The gene for albumin is a single autosomal gene, and pathological variants that affect splicing lead to premature stop, nonsense variants, and deletions that result in a defect in albumin synthesis with CAA. CAA can be fatal in the prenatal period and cause infections in early childhood. CAA is tolerated better in adulthood because of compensatory increase in other plasma proteins. Plasma lipoproteins also increase, and CAA can cause gross hyperlipidemia with severe elevations in LDL-C and hypercholesterolemia. Genetic examination of ALB is mandatory to establish the diagnosis. Early diagnosis may be important to initiate lipid-lowering treatments to avoid premature coronary artery disease. [ABSTRACT FROM AUTHOR]

Aim of the study to analyze the detection of hypercholesterolemia (HCHL) and carotid atherosclerosis (CAS), verified by duplex scanning of the carotid arteries (DSCA) in young adults (YA), and to evaluate the lipid-lowering therapy (LLT) prescription among them according to the local registry database. Materials and methods: The Duplex registry database was used for this study (n=2548). YA up to 45 years old were selected for the final analysis (n=351). Results: HCHL (> 5 mmol/L) was detected in 68.9% of patients (n=241), and only 9.5% of them received LLT (n=23). CAS was detected in 12.8% (n=45), only 17.8% of them had received LLT (n=8). Men and women differed 1.5 times by the incidence of CAS in this age range: 15.7% (30 out of 191) vs 9.4% (15 out of 160), p=0.05. Men also generally have a higher prevalence of other risk factors/diseases: HCHL (78.0% (n=149) vs 58.1% (n=93) in women, p=0.00004), hypertension (AH) (15.7% (n=30) vs 9.4% (n=15) in women, p=0,05), history of myocardial infarction (MI) (1,6% (n=3) vs 0% (n=0) in women, ns). Signs that had a significant impact on LLT intake were the following: CAS (OR 2.8 [1.09;6.6] p=0.036); AH (OR 3.1 [1.32; 7.16] p=0.009); HCHL (> 5 mmol/L) (OR 4.2 [1.12; 26.83] p=0.06); HCHL (ICD-10 code E78) (OR 5.4 [2.04; 13.7] p=0.0003); MI history (OR 22.3 [1.65;675.5] p=0.009). Conclusion: The insufficient LLT prescription in young adults with HCHL and CAS was ascertained in the present study. The use of imaging methods to clarify the degree of cardiovascular risk is advisable for low and intermediate risk patients, which include young adults. DSСA is the main method for subclinical atherosclerosis verification. LLT should be prescribed to all YA patients with CAS (in the absence of contraindications). [ABSTRACT FROM AUTHOR]

• There is no definitive diagnostic definition of hypercholesterolemia. • A unified definition and a mechanism-based classification is proposed. • It should help to better select different specialized diagnostic tests. • FH and polygenic diagnosis are restricted to those with a compatible genetic study. • A new entity: "Idiopathic primary hypercholesterolemia" is delineated. In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction. [Display omitted] [ABSTRACT FROM AUTHOR]

Iris has specific advantages, which can record all organ conditions, body construction, and psychological disorders. Traces related to the intensity or deviation of organs caused by the disease are recorded systematically and patterned on the iris and its surroundings. The pattern that appears on the iris can be recognized by using image processing techniques. Based on the pattern in the iris image, this paper aims to provide an alternative noninvasive method for the early detection of DM and HC. In this paper, we perform detection based on iris images for two diseases, DM and HC simultaneously, by developing the invariant Haralick feature on quantized images with 256, 128, 64, 32, and 16 gray levels. The feature extraction process does early detection based on iris images. Researchers and scientists have introduced many methods, one of which is the feature extraction of the gray-level co-occurrence matrix (GLCM). Early detection based on the iris is done using the volumetric GLCM development, namely, 3D-GLCM. Based on 3D-GLCM, which is formed at a distance of d = 1 and in the direction of 0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°, it is used to calculate Haralick features and develop Haralick features which are invariant to the number of quantization gray levels. The test results show that the invariant feature with a gray level of 256 has the best identification performance. In dataset I, the accuracy value is 97.92, precision is 96.88, and recall is 95.83, while in dataset II, the accuracy value is 95.83, precision is 89.69, and recall is 91.67. The identification of DM and HC trained on invariant features showed higher accuracy than the original features. [ABSTRACT FROM AUTHOR]

The article presents a case study of two siblings, where the younger brother was born small for gestational age (SGA) and developed type 2 diabetes (T2D) in childhood, while the older brother, not born SGA, exhibited severe obesity but did not develop diabetes. It explores the impact of being born SGA on the development of T2D and metabolic abnormalities, considering factors such as environmental influences, genetic background, and lifestyle choices.

The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation. [ABSTRACT FROM AUTHOR]

Objectives: To determine demographic and clinical characteristics of youth diagnosed with type 1 (T1D) or type 2 (T2D) diabetes aged ≤15 years from 1999 to 2019 in Western Australia, and examine time to first diagnosis of diabetes complications. Methods: A retrospective cohort study was conducted of patients identified from the population‐based, prospective Western Australian Children's Diabetes Database and longitudinal data extracted for available demographic and clinical variables. Patients were followed from diagnosis to transition to adult services, death, or December 31, 2019. Cox proportional hazards regression models were used to analyse time to first diagnosis of hypertension, high cholesterol or microalbuminuria, after adjusting for sex, age at diagnosis, time period of diagnosis, hemoglobin A1c, and body max index Z‐score. Results: 2438 eligible patients were identified (2209 [91%] T1D: 229 [9%] T2D). The mean age at diagnosis was lower in patients with T1D (8.5 [±4.0] vs. 12.7 [±2.0] years). A higher proportion of patients with T2D were female (58% vs. 47%) and of Aboriginal ethnicity (59% vs. 2%). The median HbA1c (interquartile range) at diagnosis was lower 8.9% [6.7, 11.5] (74 mmol/mol [50, 102]) versus 11.6% [10.1, 13.3] (103 mmol/mol [87, 122]) and mean body max index Z‐score higher (2.05 [±0.66] vs. 0.37 [±0.95]), in patients with T2D compared to T1D. Patients with T2D had a higher risk of hypertension, high cholesterol, and microalbuminuria (aHR 3.39 [95%CI:2.04, 5.63], 2.69 [95%CI:1.21, 5.98], and 19.79 [95%CI:10.99, 35.64] respectively). [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal damage. Its presentation as nephrotic syndrome (NS) during first year of life is uncommon; we describe a child with clinical and laboratory findings of NS whose renal biopsy revealed thrombotic microangiopathy (TMA). A previously healthy 4-month-old male was admitted with severe dehydration, diarrhea and anuria. Laboratory results showed electrolyte disturbances, increased serum creatinine, anemia without schistocytes, thrombocytosis, normal lactic dehydrogenase (LDH) levels, hypoalbuminemia hypercholesterolemia and decreased C3 levels. After rehydration hematuria and massive proteinuria were also documented and an initial diagnosis of NS of the first year was established. Studies seeking for infectious agents were negative. During hospitalization he continued to be oligo-anuric needing dialysis and a renal biopsy was performed, which showed TMA findings. We here considered the diagnosis of aHUS and started plasma infusions as a bridge until starting eculizumab. After two infusions urine output improved leading to discontinuation dialysis. The diagnoses of STEC infection and thrombocytopenic thrombotic purpura were ruled out. Factor B, H, I and properdin levels were normal. Antibodies against CFH negative were negative. Screening for genes causative of aHUS detected a heterozygous variant in CFHR3 of uncertain significance. On day 20, treatment was switched to eculizumab, which induced a progressive remission of the NS. This case outlines the need for a heightened diagnosis suspicion of this already rare disease since early initiation of eculizumab therapy improves its prognosis. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia (HC) is an important precursor to many cardiovascular, cerebrovascular, and peripheral vascular diseases. A report conducted by the American Heart Association showed the prevalence of HC to be 11.9%, with around 28.5 million adults age ≥ 20 years having high cholesterol levels. This study aimed to evaluate the prevalence of HC and its associated risk factors among the general population of Al-Kharj, Saudi Arabia.Method: A cross-sectional study was conducted on the general population of Al-Kharj, Saudi Arabia in 2016. The representative sample consisted of 1019 individuals, who all participated on a voluntary basis. The statistical analysis was performed using SPSS version 25.Results: The results of this study showed the prevalence of HC in the sample to be 12.5%. There was a significant moderate positive association between increasing age and the prevalence of HC (r = 0.240, P < 0.0001). Males had a significantly higher prevalence of HC (56.7%) compared to their female counterparts (43.3%) (X2 = 23.093, P ≤ 0.0001). BMI was positively and significantly associated with high cholesterol status. Participants in the overweight category had a significantly higher risk of HC (OR = 1.727; 95% CI = 1.58-1.914; P = 0.046). The non-obese (< 25 kg/m2) participants had an inverse significant association with the risk of hypercholesterolemia. (OR = 0.411; 95% CI = 0.216-0.783; P = 0.007).Conclusion: In this population-based study, the predominant risk factors of HC in Al-Kharj region were being of a Saudi nationality, male, having obesity, being unemployed, and being a civilian worker. There is a clear need for future screening studies of HC, as most previous studies have reported contradictory prevalence data (because they were conducted in different regions of KSA). Furthermore, well-designed prospective cohort studies are needed in the future to assess how the association between lifestyle behavioural factors such as dietary intake patterns and levels of physical activity may affect the relative risk of HC status. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemias are one of the major modifiable risk factors for cardiovascular disease. Familial hypercholesterolemia (FH) is the most common genetic metabolic disorder; it is estimated that around 14-34 million people worldwide have FH but only 25% of FH patients have been diagnosed. Aim: The aim of the present study was to explore the prevalence of FH in Attica region, Greece. Methods: Attica region was divided into 8 regional units. A predesigned questionnaire was used to collect demographic and clinical data. Data analysis was performed by using the Statistical Package for the Social Sciences (SPSS), ver. 20. Results: The studied sample consisted of 1578 Greek inhabitants of Attica region. The majority of the sample was women (59.9%). The mean age of the studied participants was 47.1 (±14.9) years. According to Simon Broome criteria, the probability of an FH diagnosis as unlikely is determined in 98.7% of the studied sample, probable in 0.8% of the participants or definite in 0.5% of the participants, based on this data, the prevalence of FH in Attica region, Greece is 1:200. Qualitative factors found to be associated with the onset of the disease were medication (p-value = 0.001) and hypolipidemic therapy (p-value = 0.001). The quantitative factors found to be associated with disease onset were body mass index (p-value = 0.044), and systolic (p-value = 0.001) and diastolic (p-value = 0.007) pressure. Conclusions: Based on our data, the prevalence of FH in Attica region, Greece is 1:200. Early identification of contributing factors in FH development and proper treatment is vital and reduce the risk of premature and severe atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of the community pharmacist identifying new patients with hypercholesterolaemia (HC) through a screening program (PHI‐CAPTCHA). Methods: The study begins with patients who attended any of four pharmacies in the town of Jovita (Argentina) to obtain their lipid‐lowering medication between March 1 and April 30, 2017. The genealogical trees of the patients who agreed to participate were determined. Authorisation was requested to review the cholesterolaemia records of their relatives stored in the databases of the Jovita Clinical Analysis Laboratory (1997–2015). The hypothetical efficacy of PHI‐CAPTCHA was determined as (i) the proportion of children confirmed to have HC, and (ii) the proportion of patients with at least one child with HC. Results: One hundred and thirty‐nine patients of the 274 patients who obtained their lipid‐lowering drugs from any of the four pharmacies, met the inclusion and exclusion criteria. Of the total number of patients' relatives, 532 had historical records of cholesterol readings and agreed to participate in the study. Thirty‐five per cent of children (95/270) and 26% of grandchildren (69/262) presented with HC. Forty‐eight per cent of patients had at least one child with HC. Of the 2nd generation patients of the service (original patient´s hypercholesterolaemic children), 35% of their children had HC and 50% had at least one child with this condition. A child's probability of having high cholesterol was found to double when their father also had HC (OR = 2.08, 95%CI [1.19, 3.63]). Conclusion: The results of this study indicate screening services should be offered to all HC patients, regardless of the age of their children and grandchildren. [ABSTRACT FROM AUTHOR]

Chicago is among the top five metropolitan areas in the United States where Arab Americans reside; however, we have little available data on their perceptions of personal or community health. We collected 200 community health surveys in collaboration with a community-based organization that serves mainly Arabs in Chicago's southwest suburbs. The survey evaluated perceived community and personal health. In a mostly female, married, and low-income sample, participants identified cancers, diabetes, and high blood pressure/cholesterol as the top three health problems, while alcohol abuse, drug abuse, and overweight/obesity as the top three risky behaviors within the community. Gender differences, age differences, and educational level differences were found on certain determinants of health regarding the health of the community, perceived health problems, and risky behaviors. Our data validates previous findings from the literature highlighting cancer, diabetes, and high blood pressure as health priorities among Arabs, but offers new insights into unidentified issues within the Arab American community in Southwest Chicago such as alcohol, drug abuse, and child neglect/abuse. Furthermore, our findings warrant the need for classifying Arabs as a separate minority population facing health disparities. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the effect of psychosocial aspects on self-reporting of cardiovascular diseases (CVDs). The hypotheses were that psychosocial aspects have a direct or indirect effect on health behaviors, cardiovascular disease risk factors (CVDRFs) and CVDs. A cross-sectional population-based study was conducted with a representative sample of 1100 adults from the urban area of a medium-sized municipality in southern Brazil. Structured interviews were conducted using a standardized and pre-tested questionnaire. The psychosocial aspects included scales of resilience, quality of life, sense of coherence and social support. The outcomes were CVDs and CVDRFs measured by single items asking participants whether a physician had stated that they had heart disease, high blood pressure or high cholesterol/triglycerides or were overweight (BMI≥25 kg/m2). Data analysis was based on structural equation models. The final model exhibited good fit : (χ2[57] = 155, p < 0.001, root-mean-square error of approximation [RMSEA] = 0.042, confirmatory fit index [CFI] = 0.902 and standardized root-mean-square residual [SRMR] = 0.042). Consistent with our direct effect hypothesis, favorable psychosocial aspects were inversely associated with CVDRFS (β = −0.15, p = 0.011) and with CVDs (β = −0.10, p = 0.048). The indirect effect through health behaviors was not confirmed. The findings suggest that psychosocial aspects may influence the presence of self-reported CVDs or CVDRFS. [ABSTRACT FROM AUTHOR]

Introduction: Exercise rehabilitation/training is integral in the prevention and management of chronic, lifestyle-related diseases. Poor long-term adherence to exercise by patients is a challenging problem for health professionals. Despite the evidence of appropriate supervision with improved exercise adherence, the supervision process is not adequately described in the literature. Further, the co-existing Technical and Cognitive Behavioral components of exercise supervision are commonly described separately. Methodology: The literature search included (a) reviewing the Technical Domain (TD) of exercise prescription; and (b) Cognitive Behavioral Domain (CBD) of exercise adoption and adherence. CB theories were selected based upon their scientific evidence base demonstrating efficacy in intervention trails. The FITTSBALL tool was developed combining TD and CBD identifying multiple interactions. The tool was applied to 3 case scenarios to demonstrate efficacy. Results: "FITTSBALL" combined the technical domain of "FITT" (Frequency, Intensity, Time, and Type of exercise) and the cognitive behavioral domain (combining five theories and additional constructs) explained by "SBALL" (Stage of change, Belief and Ability of the client, Limitations and Life satisfaction). The tool describes the exercise supervision process and its associations as a three dimensional "sphere" traveling in a particular trajectory. Case scenarios on exercise adoption, maintenance, and relapse are described. Discussion: The "FITTSBALL" tool developed and detailed in this article provides both a meaningful description of supervision and a logical, generic framework for exercise prescription, concentrating on adherence and behavior change. The tool could be used by all staff responsible for supervision. This approach describes how the technical "FITT" principle of prescribing exercise can coexist with a range of cognitive and behavioral theories that have been posited to describe approaches to encourage behavior change and support adherence to such changes. Many such approaches have been widely studied over recent decades using interventional trials. Conclusion: "FITTSBALL" is a logical, generic framework for exercise prescription, concentrating on adherence and behavior change. To the best of our knowledge, such a comprehensive and coherent tool has not been presented to date. Exercise training is integral in the management of chronic, lifestyle-related diseases, but long term adherence is a challenge. Exercise supervision improves adherence, but exercise supervision process is not adequately described in the literature. The tool "FITTSBALL" describes the supervision process and provides a logical, generic framework for exercise prescription and maintaining adherence to the behavior. The dynamic tool combines the traditional technical domain of "FITT" with the cognitive behavioral domain explained by "SBALL". [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of four common health conditions related to cardiovascular disease risk among Asians in Los Angeles County. Methods: A survey of Asians in Los Angeles County was conducted utilizing purposive sampling to recruit from the region's Service Planning Areas 3 and 4; these underserved areas contain high density of Asian populations. Descriptive and multivariable regression analyses were performed to explore and describe potential associations between self-reported diagnoses of prediabetes, diabetes, hypertension, and high cholesterol and body mass index (measured with non-Asian versus Asian cut points) by race/ethnicity (Chinese/Filipino/Korean/Taiwanese/Thai/Vietnamese). Results: The survey response rate was nearly 60%. The analysis included 1,377 Asians, self-identified as either Chinese (n = 700), Filipino (n = 69), Korean (n = 339), Taiwanese (n = 48), Thai (n = 115), or Vietnamese (n = 106). Results showed that, in comparison to other Asians, Filipinos had the highest risks for two of the four conditions described. Other results by subgroup affirmed a similar heterogeneous pattern of Asian health locally. Conclusions: These and other results from the survey point to potential gaps in healthcare needs of Asians, and to opportunities where local public health efforts could help increase these populations' access to cardiovascular disease-related health and social services. [ABSTRACT FROM AUTHOR]

Background Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)–infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. Methods At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. Results Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22–1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27–1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13–1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06–1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. Conclusions HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic cardiovascular disease remains a major cause of death and disability, especially for high-risk familial hypercholesterolemia individuals. PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitors) reduce low-density lipoprotein cholesterol levels and cardiovascular event rates. However, PCSK9i prescriptions are rejected at high rates by payers, and use is often delayed or eventually abandoned as a treatment option. We tested the hypothesis that acute coronary syndromes, coronary interventions, stroke, and cardiac arrest are more prevalent in patients with rejected or abandoned PCSK9i prescriptions than for those with paid PCSK9i prescriptions.Methods and Results: We identified 139 036 individuals aged ≥18 years who met the following 3 criteria: prescribed PCSK9i between August 2015 and December 2017, had claims history, and had an established date of exposure for paid, rejected, or abandoned status. To compare the effects of rejected versus paid and abandoned versus paid status, propensity score matching was performed to minimize confounding because of baseline differences in patient groups. Cox regression analyses and incidence density rates for cardiovascular events were estimated on the propensity score-matched cohorts. Patients who received 168 or more days of paid PCSK9i medication within a 12-month period were defined as paid. The hazard ratios for composite cardiovascular events outcome in propensity score-matched analyses were 1.10 (95% CI, 1.01-1.19; P=0.02) for rejected versus paid and 1.12 (95% CI, 1.01-1.24; P=0.03) for abandoned versus paid. In a stricter analysis where paid patients were defined by receiving 338 or more days of therapy within 12-months, hazard ratio was 1.16 (95% CI, 1.02-1.30; P=0.04) for rejected versus paid and 1.21 (95% CI, 1.04-1.38; P=0.03) for the abandoned versus paid status. Higher PCSK9i rejection rates were observed with women, racial minorities, and lower-income groups.Conclusions: Individuals in the rejected and abandoned cohorts had significantly increased risk of cardiovascular events compared with those in the paid cohort. Rejection, abandonment, and disparities related to PCSK9i prescriptions are related to higher cardiovascular outcome rates. [ABSTRACT FROM AUTHOR]

Background: The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.Methods: We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.Results: The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.Conclusions: In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors. [ABSTRACT FROM AUTHOR]

Background: The taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition.Objectives: This study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity.Methods: This study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.Results: Hypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96).Conclusions: A wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches. [ABSTRACT FROM AUTHOR]

Routine and selective cholesterol screening of children is an effective tool to help identify those with familial hypercholesterolemia. In children found to have elevated levels of cholesterol, secondary causes should be excluded, including hypothyroidism. Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. In this case report, we described a 2-year-old with a history of congenital hypothyroidism who was found to have severe hypercholesterolemia. A detailed medical history and appropriate screening tests are important in determining the underlying cause of elevated low-density lipoprotein cholesterol to help inform clinical decision-making. • The ideal age for universal cholesterol screening has not been determined. • Thyroid hormone has a profound effect on lipid and lipoprotein metabolism. • Secondary causes of hypercholesterolemia should be excluded before therapy initiation. [ABSTRACT FROM AUTHOR]

Background This study aimed to compare self-reported and examination-based prevalence of hypertension and hypercholesterolemia in Portugal in 2015 and to identify factors associated with the measurement error in self-reports. Methods We used data from the Portuguese National Health Examination Survey (n = 4911), that combines personal interview, blood collection and, physical examination. Sensitivity and specificity of self-reported hypertension and hypercholesterolemia were calculated. Poisson regression was used to estimate prevalence ratios (PRs) of underreport of hypertension and hypercholesterolemia according to sex, age, socioeconomic status (education and income) and general practitioner (GP) consultation in the past year. Results Sensitivity of self-reports was 69.8% for hypertension and 38.2% for hypercholesterolemia. Underreport of hypertension was associated with male gender (PR = 1.54), lack of GP consultation (PR = 1.70) and being 25–44 years old (PR = 2.45) or 45–54 years old (PR = 2.37). Underreport of hypercholesterolemia was associated with lack of GP consultation (PR = 1.15), younger age (PR = 1.83 for 25–44 age group and PR = 1.52 for 45–54 age group), secondary (PR = 1.30) and higher (PR = 1.27) education. Conclusion Self-reported data underestimate prevalence of hypertension and hypercholesterolemia. Magnitude of measurement error in self-reports varies by health conditions and population characteristics. Adding objective measurements to self-reported questionnaires improve data accuracy allowing better understanding of socioeconomic inequalities in health. [ABSTRACT FROM AUTHOR]

Sitosterolemia is a rare autosomal recessive disease characterized by a significant increase in blood plant sterol levels. Clinical manifestations usually include xanthomas, hypercholesterolemia,premature atherosclerosis and hematological abnormalities. We report here a sitosterolemia patient who presented with multiple xanthomas and profound hypercholesterolemia since 3 years old. The girl was mistreated as familial hypercholesterolemia for 6 years until correct diagnosis was made by detecting serum plant cholesterol levels. Sequence analysis revealed compound heterozygous mutations in ABCG5 gene, including the previously reported mutation c.904+1G＞A and a novel missense mutation c.1528C＞A. Although cholestyramine therapy reduced cholesterol level in association with marked regress of the xanthomas, serum plant sterol levels still remain high. Our study suggests that patients develop severe hypercholesterolemia and xanthomas at early age should be suspected of sitosterolemia. In addition, we also describe a novel missense mutation in exon 11 of the ABCG5 gene, which enriches the genetic mutation spectrum of sitosterolemia. • Clinical, molecular characteristics, and treatments of a girl with sitosterolemia. • Describes a novel missense mutation c.1528C>A in the ABCG5 gene. • Reviews the characteristics of 26 Chinese patients with sitosterolemia. [ABSTRACT FROM AUTHOR]

In light of a lack of research on the associations between vascular risk factors and cognitive function in black older adults, the authors sought to explore the relationship between two such risk factors in midlife—hypertension and hypercholesterolemia—and cognitive function later in life among black women. Purpose: This study sought to evaluate midlife hypertension and hypercholesterolemia in relation to cognitive function later in life among black women. Methods: Participants were drawn from the Nurses' Health Study and the Women's Health Study databases. In these studies, health professionals reported health information by questionnaire at baseline and at regular follow-up intervals, including diagnoses of hypertension, hypercholesterolemia, or both; and they completed telephone-based cognitive assessments later in life. Multivariable-adjusted linear regression models were used to estimate mean differences in global cognition and executive function scores, comparing women with and without a history of hypertension at midlife and women with and without a history of hypercholesterolemia at midlife. Results: Data for 363 black female health professionals were analyzed. Those with a history of hypertension or hypercholesterolemia at midlife did not have lower global cognition and executive function scores later in life compared with those without such a history, although there were trends in this direction. Conclusion: In the study sample, a history of hypertension or hypercholesterolemia at midlife was not related to worse cognitive function in later life. But there was a suggestive pattern of trends that warrants further exploration in larger studies. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 11-year-old boy who was diagnosed with familial hypercholesterolemia (FH), a severe premature atherosclerosis. Topics discussed include the medical history, the diagnosis of the patient through electrocardiography and physical examination, and the success of the percutaneous coronary intervention (PCI).

Background The significance of Lp8, that is, abnormal lipoprotein(s) detected in fraction 8 by combined high-performance liquid chromatography/gel filtration column in patients with familial lecithin:cholesterol acyltransferase (LCAT) syndrome, in relation to the severity of LCAT deficiency has not been analyzed. Objective We have studied Lp8 in a patient with primary biliary cirrhosis. Methods Plasma lipoproteins were analyzed using high-performance liquid chromatography/gel filtration column in the course of treatment of a 47-year-old female patient with primary biliary cirrhosis. Results Electrophoretic lipoprotein analyses showed massive accumulation of abnormal ß- and preß-lipoproteins with a minor lipoprotein fraction at a position near the cathode corresponding to Lp-X, on day A (status: hypercholesterolemia, LCAT activity undetectable). Chromatographic lipoprotein subfraction analysis revealed free cholesterol- and phospholipid-rich lipoproteins in fractions 1–6, corresponding to chylomicrons and very low-density lipoprotein, and phospholipid- and triglyceride-rich lipoproteins with increased free cholesterol, that is, Lp8, in fractions 7–9 (corresponding to low-density lipoprotein). On day B, after additional treatment for 7 months (status: almost normolipidemia, decreased LCAT activity), although the abnormal lipoprotein and the lipoproteins in fractions 1-6, were drastically decreased, the presence of Lp8 persisted. Conclusions Lp8 likely is a minor abnormal lipoprotein fraction in patients with mildly decreased secondary LCAT activity, as well as with severely reduced primary LCAT activity. Highlights • Lp8 is abnormal lipoprotein(s) detected in fraction 8 by high-performance liquid chromatography/gel filtration column in lecithin:cholesterol acyltransferase deficiency. • We studied Lp8 in the course of treatment of a 47-year-old female patient with primary biliary cirrhosis. • Lp8 was detected with other abnormal lipoproteins including Lp-X. • Lp8 persisted even after reduction of Lp-X and other abnormal lipoproteins. • Lp8 may be a minor lipoprotein(s) in patients with secondary disturbed lecithin:cholesterol acyltransferase activity. [ABSTRACT FROM AUTHOR]

In familial hypercholesterolemia (FH), carriers profit from presymptomatic diagnosis and early treatment. Due to the autosomal dominant pattern of inheritance, first degree relatives of patients are at 50% risk. A program to identify healthy relatives at risk of premature cardiovascular problems, funded by the Netherlands government until 2014, raised questions on privacy and autonomy in view of the chosen active approach of family members. Several countries are building cascade screening programs inspired by Dutch experience, but meanwhile, the Netherlands' screening program itself is in transition. Insight in stakeholders' views on approaching family members is lacking. Literature and policy documents were studied, and stakeholders were interviewed on pros and cons of actively approaching healthy relatives. Sociotechnical analysis explored new roles and responsibilities, with uptake, privacy, autonomy, psychological burden, resources, and awareness as relevant themes. Stakeholders agree on the importance of early diagnosis and informing the family. Dutch healthcare typically focuses on cure, rather than prevention. Barriers to cascade screening are paying an own financial contribution, limited resources for informing relatives, and privacy regulation. To benefit from predictive, personalized, and preventive medicine, the roles and responsibilities of stakeholders in genetic testing as a preventive strategy, and informing family members, need to be carefully realigned. [ABSTRACT FROM AUTHOR]

Background and aims Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1–2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence. Methods Seven cholesterol and/or mutation-based US ± reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness. Results A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels. Conclusions These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold. [ABSTRACT FROM AUTHOR]

Background and aims The cost effectiveness of cascade testing for familial hypercholesterolaemia (FH) is well recognised. Less clear is the cost effectiveness of FH screening when it includes case identification strategies that incorporate routinely available data from primary and secondary care electronic health records. Methods Nine strategies were compared, all using cascade testing in combination with different index case approaches (primary care identification, secondary care identification, and clinical assessment using the Simon Broome (SB) or Dutch Lipid Clinic Network (DLCN) criteria). A decision analytic model was informed by three systematic literature reviews and expert advice provided by a NICE Guideline Committee. Results The model found that the addition of primary care case identification by database search for patients with recorded total cholesterol >9.3 mmol/L was more cost effective than cascade testing alone. The incremental cost-effectiveness ratio (ICER) of clinical assessment using the DLCN criteria was £3254 per quality-adjusted life year (QALY) compared with case-finding with no genetic testing. The ICER of clinical assessment using the SB criteria was £13,365 per QALY (compared with primary care identification using the DLCN criteria), indicating that the SB criteria was preferred because it achieved additional health benefits at an acceptable cost. Secondary care identification, with either the SB or DLCN criteria, was not cost effective, alone (dominated and dominated respectively) or combined with primary care identification (£63, 514 per QALY, and £82,388 per QALY respectively). Conclusions Searching primary care databases for people at high risk of FH followed by cascade testing is likely to be cost-effective. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is a common genetic cause of premature cardiovascular disease (CVD). The reported prevalence rates for both heterozygous FH (HeFH) and homozygous FH (HoFH) vary significantly, and this can be attributed, at least in part, to the variable diagnostic criteria used across different populations. Due to lack of consistent data, new global registries and unified guidelines are being formed, which are expected to advance current knowledge and improve the care of FH patients. This review presents a comprehensive overview of the pathophysiology, epidemiology, manifestations, and pharmacological treatment of FH, whilst summarizing the up-to-date relevant recommendations and guidelines. Ongoing research in FH seems promising and novel therapies are expected to be introduced in clinical practice in order to compliment or even substitute current treatment options, aiming for better lipid-lowering effects, fewer side effects, and improved clinical outcomes. [ABSTRACT FROM AUTHOR]

La découverte d'une hypercholestérolémie est une situation fréquemment rencontrée en médecine générale. Le diagnostic repose sur la mise évidence d'une élévation du cholestérol lié aux lipides de faible densité [LDL] au bilan lipidique (exploration d'une anomalie lipidique). Après avoir éliminé une éventuelle hypercholestérolémie secondaire, la recherche d'arguments cliniques ou biologiques en faveur d'une hypercholestérolémie familiale monogénique (antécédent familiaux ou personnels de maladie coronaire précoce, existence de dépôts extravasculaires de cholestérol, taux de LDL très élevé) devra être une des préoccupations initiales du médecin généraliste. En cas d'éléments repérés, l'adressage du patient à un centre spécialisé s'avère nécessaire pour confirmer le diagnostic par la réalisation d'une enquête génétique et pour la mise en œuvre d'une prise en charge thérapeutique adaptée et généralement agressive. Dans les autres situations, qui sont également les plus courantes, après avoir évalué le niveau de risque cardiovasculaire du patient, la prise en charge thérapeutique des patients hypercholestérolémiques repose sur la mise en place de mesures diététiques adaptées (réduction des apports en acides gras saturés et en cholestérol alimentaire), l'instauration d'une activité physique régulière et la prise en charge optimale des autres facteurs de risque présents et modifiables (hypertension artérielle, tabac, diabète, etc.). Si, après trois à six mois, ces mesures sont insuffisantes pour ramener le LDL-cholestérol dans les objectifs thérapeutiques redéfinis en 2017 par la Haute Autorité de santé, un traitement médicamenteux pourra être initié et consistera en l'instauration en première intention d'une statine à dose faible. Habituellement, ces mesures, qu'un médecin généraliste peut facilement initier, suffisent à ramener le LDL-cholestérol des patients à faible risque cardiovasculaire ou à risque modéré dans les objectifs thérapeutiques sans qu'un avis plus spécialisé soit nécessaire. À l'opposé, pour les patients les plus sévères (risque cardiovasculaire haut ou très haut), des fortes doses de statine peuvent être nécessaires, voire le recours à des associations synergiques d'hypolipidémiants (statine + ézétimibe ou statine + résine). Un avis spécialisé est alors souvent essentiel pour atteindre les objectifs lipidiques sévères préconisés pour ces patients, notamment lorsqu'il est nécessaire de recourir à des associations, qu'il existe des intolérances aux traitements voire une indication de LDL-aphérèse. Une bonne collaboration entre médecins généralistes et spécialistes est indispensable pour assurer une prise en charge adéquate des nombreux patients hypercholestérolémiques, en adressant les cas les plus sévères ou complexes en milieu spécialisé lipidologique, les situations les plus simples mais également les plus fréquentes ne nécessitant habituellement pas d'avis spécialisé. [ABSTRACT FROM AUTHOR]

Objective: To determine whether identification of previously undiagnosed high cholesterol, hypertension, and/or diabetes during an in-home assessment impacts care seeking among Medicare beneficiaries.Data Sources/study Setting: Data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, which recruited African American and white participants across the continental United States from 2003-2007, were linked to Medicare claims.Study Design: We used panel data models to analyze changes in doctor visits for evaluation and management of conditions after participants were assessed, utilizing the study's rolling recruitment to control for secular trends.Data Extraction Methods: We extracted Medicare claims for the 24 months before through 24 months after assessment via REGARDS for 5,884 participants.Principal Findings: Semi-annual doctor visits for previously undiagnosed conditions increased by 22 percentage points (95 percent confidence interval: 16-28) 2 years following assessment. The effect was similar by gender, race, region, and Medicaid, but it may have been lower among participants who lacked a usual health care provider.Conclusions: In-home assessment of cholesterol, blood pressure, and blood glucose can increase doctor visits for individuals with previously undiagnosed conditions. However, biomarker assessment may have more limited impact among individuals with low access to care. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is a well-established risk factor for coronary heart disease, but the association between cholesterol level change and mortality is not fully understood. We aimed to investigate the association of 2 year (2002–2003 to 2004–2005) change in cholesterol with all-cause and cause-specific mortality in a population-based cohort study. Methods and findings: The study population consisted of 269,391 participants aged more than 40 years who were free of myocardial infarction, stroke and cancer using the Korean National Health Insurance Service—National Health Screening Cohort. Cholesterol levels were classified into 1st, 2nd and 3rd tertiles during each of the first and second health examinations, respectively. The participants were followed-up for all-cause and cause-specific mortality from 1 January 2006 to 31 December 2013. Compared to participants who stayed within the 2nd tertile group for cholesterol during both the first and second examinations, participants who became or maintained cholesterol levels to the 1st tertile during the second examination had increased risk of all-cause mortality [adjusted hazard ratio (aHR) with 95% confidence interval (95% CI) = 1.28 (1.18–1.38) in 1st/1st, 1.16 (1.07–1.26) in 2nd/1st and 1.47 (1.32–1.64) in 3rd/1st tertile levels, respectively]. In addition, increased or persistent high cholesterol levels to the 3rd tertile was associated with elevated risk for all-cause mortality [aHR (95% CI) = 1.10 (1.01–1.20) in 1st/2nd, 1.16(1.03–1.31) in 1st/3rd and 1.15(1.05–1.25) in 3rd/3rd tertile levels]. Conclusions: Changes in cholesterol levels in either direction to low cholesterol or persistently low cholesterol levels were associated with higher risk of mortality. Particularly, spontaneous decline in cholesterol levels may be a marker for worsening health conditions. [ABSTRACT FROM AUTHOR]

Abstract: Background: The oxidation of low‐density lipoprotein (LDL; oxLDL) appears to play a key role in the early development of atherosclerosis. Increased serum antibodies against the oxLDL (anti‐oxLDL antibodies) have been found in adults with atherosclerotic disease, as well as in healthy adults. The clinical significance and its precise role (atherogenic or atheroprotective), however, have not yet been clarified. This aim of this study was therefore to evaluate anti‐oxLDL antibodies in healthy children and adolescents with and without hypercholesterolemia. Methods: The study involved 312 subjects, aged 4–18 years, 141 with LDL cholesterol (LDL‐C) ≥130 mg/dL and 171 with acceptable LDL‐C (<110 mg/dL). Total anti‐oxLDL antibodies, total cholesterol, LDL‐C and high‐density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, lipoprotein (a) and high‐sensitivity C‐reactive protein were measured in fasting serum. The anti‐oxLDL antibodies were measured on enzyme‐linked immunosorbent assay. Results: Anti‐oxLDL antibodies were similar in the hypercholesterolemia and non‐hypercholesterolemia groups. Girls had significantly higher anti‐oxLDL antibodies compared with boys. There was no significant correlation of antibodies with age or body mass index. Increased apolipoprotein B was an important factor for lower anti‐oxLDL antibodies, while all other parameters had no significant association with anti‐oxLDL antibodies. Conclusion: In children and adolescents with hypercholesterolemia, total anti‐oxLDL antibodies cannot serve as a marker for risk for atherosclerosis or for future cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background and aims Familial hypercholesterolaemia (FH) elevates the cholesterol level and increases the risk of coronary events and death. Early detection and treatment reduce this risk. We aimed to determine the cost-effectiveness of FH screening in Poland in children, first job takers, and after an acute coronary syndrome (ACS) event, each followed by a cascade screening in the relatives of the positively-diagnosed subjects. Methods A decision tree was constructed to model the diagnosis process. We considered scenarios with and without genetic testing. A life-time Markov was built to investigate the effectiveness (life years gained, LYG; and quality-adjusted life years, QALY) and cost (public payer perspective) of treatment in FH-affected subjects. The clinical benefits result from early treatment reducing the risk of coronary heart disease (and death, in result). Model parameters were based on published data and experts' opinions. The costs (patients visits, tests, drugs) were estimated from the National Health Fund data and other publicly-available sources. Results Screening ACS patients below 55/65 years of age in men/women is the most cost-effective strategy: the cost of one LYG (QALY) amounts to 100 EUR (110 EUR). Removing the age limit or using genetic tests reduced cost-effectiveness; nonetheless, all strategies remained cost effective: the cost of one LYG or QALY was <5040 EUR, much lower than the official threshold of ca. 29,800 EUR/QALY. Conclusions Screening for FH is highly cost-effective in Poland. The strategies are complementary, and using a combination thereof is recommended. [ABSTRACT FROM AUTHOR]

Background. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results. During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions. MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models. [ABSTRACT FROM AUTHOR]

Background: For treating hypercholesterolemic in traditional medicine, Anethum graveolens seeds are used that reduce blood glucose, cholesterol and triglyceride. The aim of this study is to investigate the effect of hydroalcoholic extract of Anethum graveolens seed on the changes of testis tissue, sperm parameters in hypercholesterolemic male rats. Materials and Methods: In this study, 30 adult male rats were randomly divided into 5 groups of 6: control, hypercholesterolemic, hypercholesterolemic +alcoholic extract of Anethum graveolens seed 500 mg/kg/day, hypercholesterolemic +alcoholic extract of Anethum graveolens seed 300 mg/kg/day, healthy+alcoholic extract of Anethum graveolens seed 500 mg/kg/day. After treatment for 45 days, rats were weighed and after the dissection, sperm samples were collected from the tail epididymal and sperm parameters were studied. The testicular specimens were transferred to formalin and stained with hematoxylin-eosin. Data were analyzed using one-way ANOVA and Turkey's post- hoc tests and significant level (p<0.05) was considered. Results: In this research, in the hypercholesterolemic rats, the testicular weight was increased, but the diameter of the semnifer tubes, tubal differentiation and spermiogenese, and sperm viability were decreased compared to control (p<0.05), but in hypercholesterolemic treatment with Anethum graveolens seed these parameters were improved. Conclusion: According to the results of this study, Anethum graveolens seed has positive effects on testicular tissue and sperm parameters in hypercholesterolemic mice. [ABSTRACT FROM AUTHOR]

Background Sitosterolemia is associated with increases in intestinal sterol absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk. Objective We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case. Methods Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay. Results Of 207,926 subjects tested, 4.3% had LDL-C ≥190 mg/dL. Plasma β-sitosterol concentrations ≥8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (−29%) and β-sitosterol to 44.6 mg/L (−27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (−38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (−80% further decrease); and his β-sitosterol decreased to 14.1 mg/L (−68% further decrease). Conclusions Our data indicate that about 4% of subjects with LDL-C concentrations ≥190 mg/dL have plasma β-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients. [ABSTRACT FROM AUTHOR]

Background and aims Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. Methods We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. Results In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57–0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65–0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50–0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49–0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24–0.94; blacks, OR, 0.49, 95% CI, 0.32–0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32–0.98; blacks, OR 0.62, 95% CI, 0.43–0.90). Conclusions In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities. [ABSTRACT FROM AUTHOR]

A 23-year-old Hispanic man with no personal or family history of atherosclerotic cardiovascular disease (ASCVD) was referred for evaluation of severe hypertriglyceridemia (sHTG). Familial hypercholesterolemia (FH) was considered given alternative explanations for hypertriglyceridemia and benign family history. The patient was found to have an LDLR mutation. To highlight variability in presentation of FH. Medical record review. A 23-year-old Hispanic man was referred for evaluation of sHTG. He reported taking no medications and reported no significant past medical history other than hyperlipidemia. He denied family history of ASCVD or premature cardiovascular death. His parents were 42 and 44 years old. He described a history of "high cholesterol" in his brothers and mother but did not know further details. He presented laboratory results as follows: total cholesterol 396 mg/dL, triglyceride 648 mg/dL, HDL-C 22 mg/dL, LDL-C 223 mg/dL. Other results including comprehensive metabolic panel, thyroid function tests, urinary protein testing, hemoglobin A1c and complete blood count were normal. His lifestyle was assessed. He had recently entered a "bulking" phase at the gym, characterized by high caloric intake aimed at rapid increase in muscle bulk. He described very high carbohydrate intake. He denied anabolic steroid use or use of supplements. Given these laboratory results, dual therapy with rosuvastatin 40 mg once daily and ezetimibe 10 mg once daily was initiated. He was counseled extensively regarding lifestyle interventions, particularly in decreasing carbohydrate and fat intake. Genetic testing for FH was discussed given his notable LDL-C level, alternative explanation for sHTG, and young parental age potentially masking familial burden of disease. Genetic testing revealed a pathologic variant in LDLR (premature translational stop signal). Follow-up testing on rosuvastatin, ezetimibe and lifestyle changes revealed total cholesterol 188 mg/dL, triglyceride 129 mg/dL, HDL-C 26 mg/dL, LDL-C 138 mg/dL, apolipoprotein B 125 mg/dL. His lipoprotein(a) level was 48.3 nmol/L. All results were discussed with the patient, including recommendations for cascade genetic testing and the effectiveness of his lifestyle changes. Intensification with PCSK9-directed therapy was discussed, which he is still considering. FH has wide variability in presentation. This case illustrates the importance of considering the diagnosis when LDL-C is significantly elevated, even if other clinical aspects are less typical of FH. No [ABSTRACT FROM AUTHOR]

Nothing to disclose. None. Hypercholesterolemia is a significant cause of cardiovascular disease (CVD) worldwide. Hypercholesterolemia screening guidelines include an initial lipid panel starting at 2 years-of-age with risk factors and 10 years-of-age for all children, regardless of risk status (3). Children with PWS develop a variety of health conditions, increasing their risk of premature CVD. Thus, this population should undergo global risk factor assessment, including cholesterol screening, starting at 2 years. In 2019, the American Academy of Pediatrics management guidelines for PWS included an initial lipid panel from ages 1-5 years (2 , 4). Case 1: A full-term male infant was admitted to the NICU for hypotonia and difficulty feeding. PWS was diagnosed by microarray paternal deletion of 15q11.2-q13. At age 3 months, growth hormone was started. He developed significant hypercholesterolemia with LDL-C of 236 mg/dL at 3.5 years (Table 1). His father has hypercholesterolemia. Familial hypercholesterolemia (FH) genetic screening was negative. Renal, hepatic function and HbA1c were normal. At 3.5 years, a low normal T4 with inappropriately normal TSH was found and consistent with partial central hypothyroidism. He was treated with levothyroxine which normalized his T4; while the LDL-C improved but remained elevated. Statin therapy was deferred due to young age. Case 2: A male infant was admitted to the NICU for hypotonia and difficulty feeding. Methylation study confirmed PWS. At 5.5 years, BMI was >99th percentile and he had hypercholesterolemia. LDL-C was 198 mg/dL (Table 2). Neither parent is known to have hypercholesterolemia. FH genetic screening was negative. Thyroid and renal function were normal; however, transaminases were very elevated without cholestasis. At 7.5 years, a statin was recommended but the family opted for ezetimibe. At age 9 years, he developed HbA1c of 11.1%, and had negative antibodies consistent with Type 2 Diabetes Mellitus (T2D). He was treated with diet, insulin, and metformin. As HbA1c normalized (5.5%), the medications were discontinued. N/A. N/A In adults with PWS, hypercholesterolemia was undiagnosed in 6%, T2D in 5%, and hypertension in 3% (5). Risk factors associated with PWS contribute to premature mortality in this population and 70% die at a young age (29 +/- 16 years) (1). The presence of hypercholesterolemia or other risk factors, especially those present from an early age, greatly enhance future CVD-related risk, and represents a need for screening. [ABSTRACT FROM AUTHOR]

This study examines the association between prolonged sedentary time and breaks in sedentary time with cardiometabolic risk in 10-14-year-old children. This cross-sectional design study analysed accelerometry-determined sedentary behaviour and physical activity collected over 7 days from 111 (66 girls) UK schoolchildren. Objective outcome measures included waist circumference, fasting lipids, fasting glucose, blood pressure, and cardiorespiratory fitness. Logistic regression was used for the main data analysis. After adjustment for confounders, the odds of having hypertriglyceridaemia (P = 0.03) and an increased clustered cardiometabolic risk score (P = 0.05) were significantly higher in children who engaged in more prolonged sedentary bouts per day. The number of breaks in sedentary time per day was not associated with any cardiometabolic risk factor, but longer mean duration of daily breaks in sedentary time were associated with a lower odds of having abdominal adiposity (P = 0.04) and elevated diastolic blood pressure (P = 0.01). These associations may be mediated by engagement in light activity. This study provides evidence that avoiding periods of prolonged uninterrupted sedentary time may be important for reducing cardiometabolic disease risk in children. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC.Methods: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.Results: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p < 0.001) when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). The SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency value, 98.1% and 62.3% for positive and negative predictive values respectively.Conclusion: The SB Register criteria appears to be more useful in identifying positive cases leading to genetic testing compared to the JFHMC and US MEDPED in this Asian population. However, further research looking into a suitable diagnosis criterion with high likelihood of positive genetic findings is required in the Asian population including in Malaysia. [ABSTRACT FROM AUTHOR]

In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided. [ABSTRACT FROM AUTHOR]

In this review we outline our experience in the clinical and molecular diagnosis of familial hypercholesterolemia (FH), built up over more than three decades. We started our work by selecting FH patients on the basis of stringent clinical criteria, including extensive family studies. In most patients we confirmed the clinical diagnosis by showing a reduced LDLR activity in skin fibroblasts. After the isolation of LDLR cDNA and the characterization of the corresponding gene by the Dallas group, we started a systematic molecular investigation of our patients first using Southern blotting, and, subsequently Sanger sequencing. Up to now we have been able to identify 260 mutations of LDLR gene in more than 1000 genotyped FH patients, including 68 homozygotes. During this survey we identified 13 mutation clusters located in different geographical districts, which gave us the chance to compare the phenotype of patients carrying the most common mutations. We also found that mutations in APOB and PCSK9 genes were a rare cause of FH in our cohort. Despite our efforts, we failed to identify mutations in candidate genes in ∼20% of cases of definite FH. An exome-wide study, conducted within the context of an international collaboration, excluded the presence of other major genes in our unexplained FH cases. Recently, we have adopted sequencing technology of the next generation (NGS) with the parallel sequencing of a panel of FH targeted genes as a way of obtaining a more comprehensive picture of the gene variants potentially involved in the disease. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is one of the main risk factors for cardiovascular disease. The first line treatment for hypercholesterolemia is statin therapy. When the expected low-density lipoprotein cholesterol (LDL-C) concentration is not achieved, the pharmacotherapy may be extended by combining the statin with the cholesterol absorption inhibitor ezetimibe.Methods/design: The study is designed as a randomized, open-label, single-center, crossover study evaluating the effectiveness of combined therapy with rosuvastatin and ezetimibe for hypercholesterolemia. The study is planned to include 200 patients with hypercholesterolemia ineffectively treated with statins for at least 6 weeks. After enrollment participants are randomized into one of two arms receiving rosuvastatin and ezetimibe. In the first arm the study drug is administered in the morning (8:00 am) for 6 weeks and then in the evening for the next 6 weeks; in the second arm the study drug is administered at first in the evening (8:00 pm) for the first 6 weeks and then in the morning for the following 6 weeks. In order to minimize non-adherence to the treatment, all patients will receive the study drug free of charge. The primary outcome of the study is change in LDL-C at 6 and 12 weeks of the treatment, depending on the time of day of study drug administration. The secondary endpoints include change in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins ApoB and Apo AI, non-HDL cholesterol, small, dense (sd)-LDL cholesterol, lipoprotein(a), glucose, glycated hemoglobin, high-sensitivity C-reactive protein, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and creatine kinase at 6 and 12 weeks of the study drug treatment, as well as assessment of plasma fluorescence using stationary and time-resolved fluorescence spectroscopy at baseline and at 6 and 12 weeks of the therapy.Discussion: The RosEze trial is expected to demonstrate whether there is a significant difference in the effectiveness of the lipid-lowering therapy in reducing the concentration of cholesterol when the medications are taken in the morning compared with the evening time of day.Trial Registration: ClinicalTrials.gov, NCT02772640 . Registered on 28 March 2016. [ABSTRACT FROM AUTHOR]

Aim To assess cholesterol screening of children with Type 1 diabetes by diabetes professionals using a survey of current practice, given that National Institute of Health and Care Excellence guidelines on childhood Type 1 diabetes do not recommend cholesterol screening, yet the National Paediatric Diabetes Audit has an annual cholesterol measure (> 12 years) as a key outcome indicator. Methods An online survey was sent to 280 members of the Association of Children's Diabetes Clinicians to assess cholesterol screening practice in children. Results A total of 87 diabetes professionals (31%) responded. The results showed that 94% of respondents measured cholesterol, 33% did this annually on all children, and 7% measured fasting cholesterol. A total of 63% used no guidelines to decide treatment or further investigation. The definition of 'high' cholesterol varied from > 4.5 to > 8 mmol/l, with 40% giving no response or specific level. Only 14% of clinicians had started statin therapy in their diabetes clinic in the previous 5 years. Conclusion Whilst the majority of diabetes professionals measured cholesterol in children with Type 1 diabetes, there was marked variability in sampling, in children screened and in action taken if levels were considered abnormal. It is debatable whether cholesterol measures should be undertaken, certainly more than once, and whether cholesterol level should feature as a key outcome in the national audit in future. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors, Praluent (alirocumab [ALI]) and Repatha (evolocumab [EVO]) have been approved as adjuncts to the standard-of-care maximal-tolerated dose (MTD) of low-density lipoprotein cholesterol (LDLC)-lowering therapy (LLT), statin therapy, in heterozygous (HeFH) (ALI or EVO) or homozygous (EVO) familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient (both). Since LDLC lowering has been revolutionized by ALI and EVO, specialty pharmaceutical pricing models will be applied to a mass market.Methods: We applied US Food and Drug Administration (FDA) and insurance eligibility criteria for ALI and EVO to 1090 hypercholesterolemic patients serially referred over 3 years who then received ≥2 months maximal-tolerated dose of standard-of-care LDL cholesterol-lowering therapy (MTDLLT) with follow-up LDLC ≥70 mg/dL. MTDLLT did not include ALI or EVO, which had not been commercially approved before completion of this study.Results: Of the 1090 patients, 140 (13%) had HeFH by clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite ≥2 months on MTDLLT, meeting FDA insurance criteria for ALI or EVO therapy. Another 51 (5%) patients were statin intolerant, without HeFH or CVD.Conclusion: If 13% of patients with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT are eligible for ALI or EVO, then specialty pharmaceutical pricing models (~$14,300/year) might be used in an estimated 10 million HeFH-CVD patients. Whether the health care savings arising from the anticipated reduction of CVD events by ALI or EVO justify their costs in populations with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT remains to be determined. [ABSTRACT FROM AUTHOR]

The role of gut microbiota in the development of metabolic illnesses has been abundantly demonstrated. Recent studies suggest that gut microbiota alterations may also be related to the development of hypercholesterolemia. Therefore, we aimed to assess differences in the gut bacterial community profiles between hypercholesterolemic subjects and controls. Thirty cases diagnosed with hypercholesterolemia and 27 normocholesterolemic controls were included. A fasting whole blood sample was obtained to determine the lipid profile. In parallel, stool samples were collected and total DNA was isolated to assess the bacterial community profiles by denaturing gradient gel electrophoresis (DGGE). In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to evaluate the richness and diversity of bacterial communities. As expected, serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol were significantly higher in the cases compared with controls. Moreover, DGGE analysis showed a lower richness and diversity of bacterial communities in hypercholesterolemic subjects. In conclusion, our results showed differences in the profiles of bacterial communities between hypercholesterolemic subjects and controls, suggesting a possible role of the gut microbiota in the development of hypercholesterolemia. [ABSTRACT FROM AUTHOR]