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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]

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]

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: 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]

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]

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).

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]

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]

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]

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: 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]

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]

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]

This article describes the evolution of our understanding of familial hypercholesterolemia (FH) in the Central, Eastern, and Southern Europe (CESE) region, and the dissemination of this understanding to other countries. Using the ScreenPro FH project as an example, we would like to illustrate the progression from national objectives, to regional networking and, finally, to international collaboration via the Familial Hypercholesterolemia Studies Collaboration (FHSC) project under the leadership of the European Atherosclerosis Society (EAS). It is essential to improve our ability to diagnose FH. In this regard, the EAS and its FHSC project must be commended for their educational and organizational activities which, above all, are dedicated to the creation of a global FH patient registry. In the CESE region, FH diagnostics and treatment situation are markedly different than in Western Europe or North America. Since the Czech MedPed project (Make Early Diagnoses to Prevent Early Deaths in Medical Pedigrees) has been so successful (with results not only comparable to, but, for some parameters, even surpassing the results of many Western countries) we decided to apply the Czech experience to the CESE region. Thus, the ScreenPro FH project was created. The aim of ScreenPro FH is to create a specialist network in the CESE region. The primary objective of the ScreenPro FH project was to dramatically reduce the number of premature deaths due to clinical complications of atherosclerosis in FH patients. At present, ScreenPro FH comprises 18 member countries with a total population of 500,000,000; which, in terms of the FH population, represents 1-2 million patients. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to update estimates of the health and economic impact of clinical services recommended for the primary prevention of cardiovascular disease (CVD) for the comparative rankings of the National Commission on Prevention Priorities, and to explore differences in outcomes by sex and race/ethnicity.Methods: We used a single, integrated, microsimulation model to generate comparable results for 3 services recommended by the US Preventive Services Task Force: aspirin counseling for the primary prevention of CVD and colorectal cancer, screening and treatment for lipid disorders (usually high cholesterol), and screening and treatment for hypertension. Analyses compare lifetime outcomes from the societal perspective for a US-representative birth cohort of 100,000 persons with and without access to each clinical preventive service. Primary outcomes are health impact, measured by the net difference in lifetime quality-adjusted life years (QALYs), and cost-effectiveness, measured in incremental cost per QALY or cost savings per person in 2012 dollars. Results are also presented for population subgroups defined by sex and race/ethnicity.Results: Health impact is highest for hypertension screening and treatment (15,600 QALYs), but is closely followed by cholesterol screening and treatment (14,300 QALYs). Aspirin counseling has a lower health impact (2,200 QALYs) but is found to be cost saving ($31 saved per person). Cost-effectiveness for cholesterol and hypertension screening and treatment is $33,800 per QALY and $48,500 per QALY, respectively. Findings favor hypertension over cholesterol screening and treatment for women, and opportunities to reduce disease burden across all services are greatest for the non-Hispanic black population.Conclusions: All 3 CVD preventive services continue to rank highly among other recommended preventive services for US adults, but individual priorities can be tailored in practice by taking a patient's demographic characteristics and clinical objectives into account. [ABSTRACT FROM AUTHOR]

The screening measures to identify various cardiovascular risks related to hyperglycemia, hypertension and hypercholesterolemia are involves both anatomic assessments like anthropometric measures or body's physiological evaluation by performing biochemical parameters. In this regard "lipid accumulation product" (LAP) has surfaced as a marker to incorporate both these anatomic and physiological considerations. Objectives: 1. To measure the LAP differences between subjects having normal and higher levels of glucose, total cholesterol, age, carotid intima media thickness and subjects with and without hypertension. 2. To compare BMI and LAP in terms of effectiveness as a screening marker for diagnosis of diabetes mellitus and hypertension through ROC curve calculation. Design: Cross-sectional analysis. Place and duration of study: This study was carried out at the departments of pathology, PNS RAHAT hospital from Jan-2011 to Oct-2011. Subjects and methods: After several exclusions including know diabetics a total of 202 subjects were enrolled to undergo sampling for Fasting blood glucose, and lipids in exact medical fasting status. These subjects were later evaluated for their various anthropometric measurements including BMI and WHpR (Wait to hip ratio) as per the WHO protocol. Then the individuals went to radiology department where carotid intima media thickness measurements were made by experienced radiologist. LAP (Lipid accumulation products) score was calculated as: LAP score (Male) = [WC (cm) - 65] × triglycerides (mmol/L) LAP score (Female) = [WC (cm) - 58] × triglycerides (mmol/L). LAP scores, BMI. WHpR and mean CIMT readings were grouped as per their high or low results. Results: Out of BMI, WHpR and LAP score, only groups based upon LAP score were observed to be significantly different for fasting blood glucose, total cholesterol and mean CIMT levels. Hypertensive subjects had higher LAP scores and WHpR than non-hypertensive subjects; however, BMI differences were not considered significant. One way ANOVA shows the LAP scores progressively rising form normoglycemic subjects {58.38 (95% CI: 51.08-65.67)} to subjects having IFG {70.94(95%CI: 60.88-81.00)} to newly diagnosed diabetes mellitus {101.59(95%CI: 78.35-124.83)}.[P=0.001] The AUCs for diagnosing hypertension was higher for LAP scores than for BMI and WHpR [{(LAP score: 0.648 (95% CI: 0.536-0.760), p= 0.027} vs {(WHpR: 0.588 (95% CI: 0.466-0.709), p= 0.191} vs {(BMI: 0.541 (95% CI: 0.412-0.670), p=0.545}]. Similarly, the AUCs for BMI and WHpR were lower than that of LAP score for predicting a diagnosis of diabetes mellitus [{(LAP score: 0.584 (95% CI: 0.502-0.665), p= 0.047} vs {(BMI: 0.531 (95% CI: 0.448-0.613), p=0.468} vs {WHpR: 0.518 (95% CI: 0.435-0.601), p=0.668}]. Conclusion: LAP scores were higher in subjects with established cardiovascular risks like hyperglycemia, hypercholesterolemia, accelerated atherosclerosis and hypertension that simple anthropometric indices like BMI and WHpR. [ABSTRACT FROM AUTHOR]

The author comments on the vital role of low-density lipoprotein cholesterol (LDL-C) on familial hypercholesterolemia (FH) and premature coronary heart disease (CHD) patients. The topics discussed include the challenges and difficulties epxrienced by physicians in tracking and diagnosing FH during its early stages, the effectiveness of genetic testing in FH diagnosis, and the polygenic cause of FH.

Background: Apolipoprotein E-deficient (ApoE(-/-)) rodents spontaneously develop severe hypercholesterolemia and increased aortic stiffness, both accepted risk factors for cardiovascular morbidity and mortality in humans. In patients with resistant hypertension renal denervation (RDN) may improve arterial stiffness, however the underlying mechanisms are incompletely understood. This study investigates the impact of RDN on aortic compliance in a novel atherosclerosis prone ApoE(-/-)-rat model.Methods: Normotensive, 8 weeks old ApoE(-/-) and Sprague-Dawley (SD) rats were subjected to bilateral surgical RDN (n = 6 per group) or sham operation (n = 5 per group) and fed with normal chow for 8 weeks. Compliance of the ascending aorta was assessed by magnetic resonance imaging. Vasomotor function was measured by aortic ring tension recordings. Aortic collagen content was quantified histologically and plasma aldosterone levels were measured by enzyme-linked immunosorbent assay (ELISA).Results: After 8 weeks, ApoE(-/-)-sham demonstrated a 58 % decrease in aortic distensibility when compared with SD-sham (0.0051 ± 0.0011 vs. 0.0126 ± 0.0023 1/mmHg; p = 0.02). This was accompanied by an impaired endothelium-dependent relaxation of aortic rings and an increase in aortic medial fibrosis (17.87 ± 1.4 vs. 12.27 ± 1.1 %; p = 0.006). In ApoE(-/-)-rats, RDN prevented the reduction of aortic distensibility (0.0128 ± 0.002 vs. 0.0051 ± 0.0011 1/mmHg; p = 0.01), attenuated endothelial dysfunction, and decreased aortic medial collagen content (12.71 ± 1.3 vs. 17.87 ± 1.4 %; p = 0.01) as well as plasma aldosterone levels (136.33 ± 6.6 vs. 75.52 ± 8.4 pg/ml; p = 0.0003). Cardiac function and metabolic parameters such as hypercholesterolemia were not influenced by RDN.Conclusion: ApoE(-/-)-rats spontaneously develop impaired vascular compliance. RDN improves aortic distensibility and attenuated endothelial dysfunction in ApoE(-/-)-rats. This was associated with a reduction in aortic fibrosis formation, and plasma aldosterone levels. [ABSTRACT FROM AUTHOR]

Background: Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol ≥190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement.Objectives: This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level.Methods: Three genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database.Results: Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol ≥190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol ≥190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers.Conclusions: Among participants with LDL cholesterol ≥190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD. [ABSTRACT FROM AUTHOR]

Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio. [ABSTRACT FROM AUTHOR]

The article discusses the scientific statement from the American Heart Association (AHA) regarding familial mhypercholesterolemia (FH) , an autosomal-dominant genetic disease and recognized as a cause of premature atherosclerotic coronary heart disease. Topics mentioned include the importance of patient perspectives in the optimization of care, studies exploring the quality of life (QOL) of patients, and atherosclerosis and detection of myocardial schemia.

Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis. [ABSTRACT FROM AUTHOR]

Here's how to spot the red flags that could signal your patient is at risk and steps you can take to potentially extend his or her life. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is one of the most common single gene disorders, which is mostly inherited as an autosomal dominant trait. The physical signs of FH are elevated low density lipoprotein cholesterol (LDL-C), elevated total cholesterol (TC) levels and tendon xantomas. Identification and early treatment of affected individuals is desirable and in lack of physical symptoms DNA-based diagnosis provides confirmation of diagnosis and enables early patient management. The majority of FH cases are caused by mutations in four genes ( APOB, LADLR, PCSK9, and LDLRAP1). There are commercial kits available for testing of the 20 most common FH causing mutations, but the spectrum of disease-causing mutations is quite diverse in various populations and these tests cover only a minority of disease-causing genetic variants. There is therefore a need to determine the full spectrum of mutations in LDLR, APOB, PCSK9, and LDLRAP1 genes in each population. Here we report mutations found in 16 patients with suspected FH in a sample from the Genome Database of the Latvian population enrolled at the Latvian Centre of Cardiology. We used the next generation sequencing approach to determine the full spectrum of mutations in coding regions of LDLR, APOB, PCSK9, and LDLRAP1. In total we found 22 missense mutations, from which only rs5742904 (Arg3527Gln) in APOB gene had been previously described as a FH-causing mutation confirming FH in one patient. Possible FH-causing mutations however, were identified in the majority of patients. The conclusion is that the most commonly employed commercial mutation panel is not sufficient for diagnosis of FH patients and NGS can help to identify FH-causing mutations in the Latvian population. [ABSTRACT FROM AUTHOR]

Aims Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes. Methods and results Sixty-five patients with no stenosis > 30% on invasive coronary angiography were categorized into diabetes (19) and non-diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left-ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 ± 39.7 vs. 91.5 ± 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 ± 39.7 vs. 90.3 ± 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 ± 1.90 vs. 8.59 ± 1.91° P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 ± 0.76 vs. 2.84 ± 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = -0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist-hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02). Conclusion Patients with diabetes have increased LV mass, LV torsion, and decreased M PR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes. [ABSTRACT FROM AUTHOR]

PURPOSE Continuity of care is considered a core element of high-quality primary care, but its impact on mortality and health care costs is unclear. We aimed to determine the impact of continuity of care on mortality, costs, and health outcomes in patients with newly diagnosed cardiovascular risk factors. METHODS We conducted a cohort study of a 3% nationwide random sample of Korean National Health Insurance enrollees. A total of 47,433 patients who had received new diagnoses of hypertension, diabetes, hypercholesterolemia, or their complications in 2003 or 2004 were included. We determined standard indices of continuity of care–most frequent provider continuity (MFPC), modified, modified continuity index (MMCI), and continuity of care index (COC)–and evaluated their association with study outcomes over 5 years of follow-up. Outcome measures included overall mortality, cardiovascular mortality, incident cardiovascular events, and health care costs. RESULTS The multivariable-adjusted hazard ratios (HRs) for all-cause mortality, cardiovascular mortality, incident myocardial infarction, and incident ischemic stroke comparing participants with COC index below the median to those above the median were HR = 1.12 (95% CI, 1.04-1.21), 1.30 (1.13-1.50), 1.57 (1.28- 1.95), and 1.44 (1.27-1.63), respectively. Similar findings were obtained for other indices of continuity of care. Lower continuity of care was also associated with increased inpatient and outpatient days and costs. CONCLUSIONS Lower indices of continuity of care in patients with newly diagnosed hypertension, diabetes, and hypercholesterolemia were associated with higher all-cause and cardiovascular mortality, cardiovascular events, and health care costs. Health care systems should be designed to support long-term trusting relationships between patients and physicians. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to combine clinical criteria and next-generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia ( FH). Design, setting and subjects A total of 77 subjects with a Dutch Lipid Clinic Network score of ≥3 (possible, probable or definite FH clinical diagnosis) were recruited from the Lipid Clinic at Sahlgrenska Hospital, Gothenburg, Sweden. Next-generation sequencing was performed in all subjects using SEQPRO LIPO RS, a kit that detects mutations in the low-density lipoprotein receptor ( LDLR), apolipoprotein B ( APOB), proprotein convertase subtilisin/kexin type 9 ( PCSK9) and LDLR adapter protein 1 ( LDLRAP1) genes; copy-number variations in the LDLR gene were also examined. Results A total of 26 mutations were detected in 50 subjects (65% success rate). Amongst these, 23 mutations were in the LDLR gene, two in the APOB gene and one in the PCSK9 gene. Four mutations with unknown pathogenicity were detected in LDLR. Of these, three mutations (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH, but their pathogenicity has not been proved. The fourth, a mutation in LDLR affecting a splicing site (exon 6-intron 6) has not previously been reported; it was found to segregate with high cholesterol levels in the family of the proband. Conclusions Using a combination of clinical criteria and targeted next-generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing-site mutation in the LDLR gene. [ABSTRACT FROM AUTHOR]

Background: Although hypercholesterolemia is a major risk factor for coronary artery disease (CAD), only limited data are available regarding its direct effect on myocardial function apart from CAD. The aim of this study was to evaluate LV systolic function using speckle-tracking echocardiography and investigate the relationship between hypercholesterolemia and myocardial function. Methods: Twenty-eight rabbits were randomly divided into three groups: 8 were fed normal chow for 3 months (group 1) and the remaining 20 were fed an atherogenic diet for 2 (group 2) or 3 months (group 3). Global systolic radial, circumferential and longitudinal peak strain were calculated. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and myocardial cholesterol levels were measured. Results: Global systolic longitudinal strain were both decreased in the group 2 and 3 (P < 0.001), whereas radial strain were increased (P < 0.001) compared with group 1. Global circumferential strain in the group 3 was significantly reduced (P < 0.001). Serum and myocardial cholesterol concentration markedly increased in the group 2 and group 3 (P < 0.001). There was a significant inverse correlation between longitudinal strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.723, r = - 0.794, r = - 0.700, P both < 0.001). A significant negative correlation was also noted between circumferential strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.518, P = 0.007; r = - 0.691, P < 0.001; r = - 0.659, P < 0.001). A significant positive correlation was found between radial strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = 0.432, P = 0.028; r = 0.602, P = 0.001; r = 0.469, P = 0.016). Conclusion: Although LV morphology and ejection fractions were not different among the three groups, elevated concentration of cholesterol, especially in serum LDL-C, was significantly associated with LV systolic dysfunction. The findings also indicate that reductions in longitudinal was the first appeared, followed by circumferential, and was compensated for by increasing radial strain. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is a congenital disorder of lipid metabolism characterized by a marked elevation of the plasma concentration of LDL (low-density lipoprotein) cholesterol beginning in childhood and by the early onset of coronary heart disease. It is among the commonest genetic disorders, with an estimated prevalence in Germany of at least 1 per 500 persons. Method: Review of pertinent literature retrieved by a selective search. Results: FH is underdiagnosed and undertreated in Germany. It is clinically diagnosed on the basis of an elevated LDL cholesterol concentration (>190 mg/ dL [4.9 mmol/L]), a family history of hypercholesterolemia, and early coronary heart disease, or the demonstration of xanthomas. The gold standard of diagnosis is the identification of the underlying genetic defect, which is possible in 80% of cases and enables the identification of affected relatives of the index patient. The recommended goals of treatment, based on the results of observational studies, are to lower the LDL cholesterol concentration by at least 50% or to less than 100 mg/dL (2.6 mmol/L) (for children: <135 mg/dL [3.5 mmol/L]). The target value is lower for patients with clinically overt atherosclerosis (<70 mg/dL [1.8 mmol/L]). Statins, combined with a healthpromoting lifestyle, are the treatment of choice. Lipoprotein apheresis is used in very severe cases; its therapeutic effects on clinical endpoints and its side effect profile have not yet been documented in randomized controlled trials. Conclusion: Familial hypercholesterolemia is a common disease that can be diagnosed simply and reliably on clinical grounds and by molecular genetic testing. Timely diagnosis and appropriate treatment can lower the risk of atherosclerosis in heterozygous patients to that of the general population. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the expression of the intercellular adhesion molecule 1 (ICAM-1) in the sclera and choroid of hypercholesterolemic rabbits. Methods: New Zealand rabbits were divided into two groups: the normal diet group (NG), with 8 rabbits (8 eyes), was fed a standard rabbit diet for 4 weeks; the hypercholesterolemic group (HG), with 13 rabbits (13 eyes), was fed a 1% cholesterol- enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the start of the experiment and at the euthanasia time. HG and NG animals were euthanized after 8th week and 4th week, respectively. Their eyes were stained with hematoxylin-eosin and underwent histological, histomorphometric and immunohistochemical analyses with ICAM-1 antibody. Results: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). The histological analysis with hematoxylin-eosin revealed a large number of macrophages in the HG sclera-choroid complex. Moreover, a significant increase in the HG sclera and choroid thickness was observed in relation to NG (p<0.001). There was a significant increase in the ICAM-1 expression in HG sclera and choroid in relation to NG. Conclusion: This study has revealed that the hypercholesterolemic diet induces an increase in the ICAM-1 expression in the rabbits' sclera and choroid. [ABSTRACT FROM AUTHOR]

The severe hypercholesterolemia phenotype includes all patients with marked elevation of low-density lipoprotein cholesterol (LDL-C) levels. The most common cause is autosomal dominant hypercholesterolemia, an inherited disorder caused by mutations either in LDL receptor, apolipoprotein B (APOB), or proprotein convertase subtilisin kexin type 9 (PCSK9) genes. However, it is now known that many subjects with severe inherited hypercholesterolemia have no defects in these genes. These cases are caused either by mutations in genes yet to be identified or are consequences of polygenic, epigenetic, or acquired defects. Because the clinical consequences of extreme hypercholesterolemia are the same no matter the cause, the focus should be on the identification of subjects with severe hypercholesterolemia, followed by phenotypic screening of family members. Genetic screening is not necessary to diagnose or initiate treatment for the severe hypercholesterolemia phenotype. Management of severe hypercholesterolemia is based on risk factor modification and use of multiple lipid-lowering medications. Lipoprotein apheresis is indicated for coronary artery disease (CAD) patients taking maximally tolerated therapy and with LDL-C levels >200 mg/dl (>300 mg/dl if without CAD). A microsomal triglyceride transfer protein inhibitor and an antisense oligonucleotide against APOB have recently been approved for use in subjects with clinically diagnosed homozygous familial hypercholesterolemia. PCSK9 inhibitors, currently in phase II and III trials, lower LDL-C up to an additional 70% in the setting of maximally tolerated medical therapy and have the potential to reduce LDL-C to <70 mg/dl in most patients. Early identification of affected individuals and aggressive treatment should significantly reduce the burden of cardiovascular disease in society. [Copyright &y& Elsevier]

Familial hypercholesterolemia is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C). It is mainly caused by mutations of the low-density lipoprotein receptor (LDLR) gene. Currently, the methods of whole genome sequencing or whole exome sequencing for screening mutations in familial hypercholesterolemia are not applicable in China due to high cost. We performed targeted exome sequencing of 167 genes implicated in the homozygous phenotype of a proband pedigree to identify candidate mutations, validated them in the family of the proband, studied the functions of the mutant protein, and followed up serum lipid levels after treatment. We discovered that exon 9 c.1268 T>C and exon 8 c.1129 T>G compound heterozygous mutations in the LDLR gene in the proband derived from the mother and father, respectively, in which the mutation of c.1129 T>G has not been reported previously. The mutant LDL-R protein had 57% and 52% binding and internalization functions, respectively, compared with that of the wild type. After 6 months of therapy, the LDL-C level of the proband decreased by more than 50% and the LDL-C of the other family members with heterozygous mutation also reduced to normal. Targeted exome sequencing is an effective method for screening mutation genes in familial hypercholesterolemia. The exon 8 and 9 mutations of the LDLR gene were pedigree mutations. The functions of the mutant LDL-R protein were decreased significantly compared with that of the wild type. Simvastatin plus ezetimibe was proven safe and effective in this preschool-age child. [ABSTRACT FROM AUTHOR]

Background: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward β-oxidation. Objective: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids. Design: Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[13C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [13C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion. Results: The emulsified fat resulted in earlier (>1 h) and sharper chylomicron and [13C]fatty acid peaks in plasma than in spread fat in both groups (P < 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 ± 0.7 compared with 7.1 ± 0.9 mg/L; P < 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 ± 24 nm) compared with the spread fat (P < 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper 13CO2 appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P < 0.05) and from 40% to 57% in obese subjects (P < 0.01). Conclusion: This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid /β-oxidation in humans with different BMIs. This trial was registered at clinical-trials.gov as NCT01249378. Am J Clin Nutr 2013;97:23-36. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia (HC) is a major risk factor in the development of coronary heart disease (CHD). Serum cholesterol is directly related to complications and mortalities associated with heart diseases. There are a few studies that describe HC among youths in the Arab Gulf countries. We sought to evaluate HC among young healthy university students to assess their risk of developing CHD. Methods: Lipid profile of 166 students between the ages of 16- 30 years (Mean: 20.49±2.96) were examined and blood glucose, total protein, albumin, thyroid stimulating hormone (TSH) and the inflammation marker high sensitivity CRP (hsCRP) were determined. Each volunteer filled a questionnaire about her/his lifestyle and personal and family medical histories and height and weight were measured to determine body mass index (BMI). The data were analyzed using SPSS version 17. Chi-Square was used to determine the relation between categorical variables. A p-value <0.05 was considered statistically significant. Results: According to the American Heart Association criteria, 44 (26.5%) students were identified with primary hypercholesterolemia (PHC) in the first testing round. After proper health counseling, the same tests were repeated after 2-3 weeks in all 44 hypercholesterolemic students. We found only 26 (15.6%) of them to be hypercholesterolemic. There was a significant relation between high total cholesterol (TC) and high TC/HDLC, as well as high or very high hsCRP and high TC/HDLC (both, p<0.001). Males tend to have higher TC/HDLC and hsCRP than females (both p0.002 and 0.005, respectively). Family history of CHD was found in 8 students and obesity was recorded in 5 volunteers. Conclusion: The results necessitate further studies in determining the cause of PHC. We predict a genetic element contributing to the high percentage of PHC in the current study. [ABSTRACT FROM AUTHOR]

A 20-d-old boy was referred to our department because of hyperthyrotropinemia at neonatal mass screening and diagnosed with neonatal transient hyperthyrotropinemia. A follow-up examination when the patient was 5 mo old revealed severe hypercholesterolemia. Familial hypercholesterolemia was first suspected because of the patient's significantly high levels of total and low-density lipoprotein cholesterol. The parent's serum lipid profiles were examined and found to be normal. He was completely breast-fed until 6 mo of age. Breast milk was still the main source of food for a period following weaning. At 14 mo old, the patient was weaned completely from breast milk, and his serum cholesterol levels decreased dramatically. According to the normal lipid profiles of the patient's parents and the spontaneous normalization of serum cholesterol levels after complete weaning from breast milk, breast-feeding was suggested to be responsible for his transient severe hypercholesterolemia. It is well documented that breast-fed infants have higher serum cholesterol levels than formula-fed infants. However, there is no reported case with severe hypercholesterolemia equivalent to or higher than the levels observed in the case of familial hypercholesterolemia. Although the exact mechanism is unknown, it is necessary to consider that a small number of cases develop severe hypercholesterolemia related to breast-feeding. [ABSTRACT FROM AUTHOR]

lnterindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 ± 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol ≥ 240 mg/dL) and 120 normolipidemic healthy controls (40 ± 10 years old; total cholesterol ≤ 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLE The genotype distribution for 3435C>T variant of ABCBI in HC patients (CC: 49%, CT: 37%, TT: 14%) and controls (CC: 41%, CT: 48%, TT: 11%) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73%, AG: 27%, GG: 0%) and controls (AA: 71%, AG: 29%, GG: 0%) was equivalent (P=0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4%, AG: 41%, GG: 55%) and controls (AA: 4%, AG: 47%, GG: 49%) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCBI), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations. [ABSTRACT FROM AUTHOR]

Objective To determine the fraction of individuals with high total serum cholesterol who get diagnosed and effectively treated in eight high- and middle-income countries. Methods Using data from nationally representative health examination surveys conducted in 1998-2007, we studied a probability sample of 79039 adults aged 40-79 years from England, Germany, Japan, Jordan, Mexico, Scotland, Thailand and the United States of America. For each country we calculated the prevalence of high total serum cholesterol (total serum cholesterol ≥6.2 mmol/l or ≥ 240 mg/dl) and the mean total serum cholesterol level. We also determined the fractions of individuals being diagnosed, treated with cholesterol-lowering medication and effectively controlled (total serum cholesterol <6.2 mmol/l or < 240 mg/dl). Findings The proportion of undiagnosed individuals was highest in Thailand (78%; 95% confidence interval, CI: 74-82) and lowest in the United States (16%; 95% CI: 13-19). The fraction diagnosed but untreated ranged from 9% in Thailand (95% CI: 8-11) to 53% in Japan (95% CI: 50-57). The proportion being treated who had attained evidence of control ranged from 4% in Germany (95% CI: 3-5) to 58% in Mexico (95% CI: 54-63). Time series estimates showed improved control of high total serum cholesterol over the past two decades in England and the United States. Conclusion The percentage of people with high total serum cholesterol who are effectively treated remains small in selected high- and middle-income countries. Many of those affected are unaware of their condition. Untreated high blood cholesterol represents a missed opportunity in the face of a global epidemic of chronic diseases. [ABSTRACT FROM AUTHOR]

The primary purposes of this study were to: 1) examine the accuracy for referral of two portable lipid analyzers (PLAs) in an old order Mennonite population through a comparison to a national standardized reference laboratory, 2) examine the relationship of total cholesterol values with other known cardiovascular risk factors, and 3) foster the continued participatory model of health care service in this community. The self-selected sample was composed of 42 adult members of an old order Mennonite community residing in south central Kentucky. A descriptive correlational design was used in this study. There were clinically relevant variations in the total cholesterol and LDL-C in both of the analyzers. Additionally, there was a correlation between total cholesterol values and age. The study also facilitated the participatory model used with this community previously as the community members assisted in planning, implementing, and evaluating this project. [ABSTRACT FROM AUTHOR]

Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI) environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC) microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of the two primary cardiovascular risk factors, hypertension and hypercholesterolaemia, are well established. Nevertheless, according to earlier analyses of representative health questionnaire and examination surveys in 1984, 1988 and 1991, control of risk factors in the sense of normalized values through drug therapy did not improve to any relevant degree in former West Germany. The National Health Survey of 1998 now allows the reconsideration of the hypothesis that medical treatment has been improving and lead to a reduction of risk factor values measured in the population. Methods: Datasets of independent cross-sectional studies in 1984, 1988, 1991 and 1998 with net random sample sizes between 3458 and 5335 were analysed for actual (persons with elevated values and persons successfully treated) and population (persons with elevated values) prevalence, awareness of the risk factors under question, treatment coverage (risk factor aware and treated) and effectiveness (risk factor aware, treated and normalized), and the resulting parameters of controlled (successfully treated persons among actual prevalence) and uncontrolled prevalence (persons with elevated values among actual prevalence), respectively. Thresholds chosen were blood pressure values ≥160/95 mmHg for hypertension and values ≥250 mg/dl for hypercholesterolaemia. Regarding medication, the answer of 'one to two times weekly' or more was considered to indicate a relevant drug intake. Results: For hypertension the population prevalence (population 30-69 years old) increased significantly (P < 0.0001) from 19.6% to 24.0% between 1984 and 1998, whereas the actual prevalence rose less steeply but still significantly (P < 0.0002) from 32.5% to 34.4%. For hypercholesterolaemia the population prevalence stagnated at 37.0% (1998), whereas the actual prevalence was 47.5% in 1998 (39.1% in 1984; P < 0.0001). For hypertension treatment, coverage improved from 45.4% to 63.0%, but treatment effectiveness decreased from 51.7% to 41.3%, both trends being highly significant. For hypercholesterolaemia, awareness increased from 18.3% to 57.6%, but treatment coverage decreased from 33.5% to 15.5%, whereas treatment effectiveness improved from 23.8% to 47.7%, all trends being highly significant (P < 0.0001). Conclusions; The results do not support the hypothesis that medical care for the large population at cardiovascular risk in (Western) Germany was adequate and successful in the 1980s and 1990s. [ABSTRACT FROM AUTHOR]

To evaluate the effect of a letter intervention that was send to both the participants of a population screening and their general practitioners. We also tested what predicting variables influenced the GP to actually prescribe blood pressure lowering drugs (BPLD) or lipid lowering drugs (LLD). The study design was cross sectional, in the PREVEND outpatient clinic in Groningen University Hospital, the Netherlands. We used the clinical data of the 8592 subjects that participated in the first screening of the PREVEND study. Data on drug use was collected from community pharmacies. Drug use was measured the year before and after the screening with the subsequent intervention letter. As control population without intervention, we used the data from the InterAction DataBase (IADB) standardized for the population characteristics of the intervention group. The letter intervention was sent to participants who had shown after screening to have either an elevated blood pressure or plasma cholesterol, and the letter contained the advice to use a BPLD or LLD. Main outcome measures were proportion of patients prescribed BPLD and/or LLD in the year before and after the intervention, and variables that influence the GP to prescribe BPLD and LLD. Data from the community pharmacy were available from 7567 (88%) subjects. 397 participants (5.2%) received a letter with advice to start a BPLD, and 326 participants (4.3%) received a letter with advice to start a LLD. The prevalence of patients who were using BPLD and LLD before the intervention was not significantly different between the intervention and control group, 16.6 (CI 95% 15.8 –17.5) vs 16.0 and 4.8 (4.4–5.3) vs 4.6, respectively. After the letter intervention, the prevalence of BPLD use was higher in the intervention group compared with the control group (19.4 [18, 5–20, 3] vs 17.0%), as was the prevalence of LLD use (7.1[6.5–7.7) vs 5.4%). The same held true for the incidence of BPLD (3.4[3.0–3.8] vs 2.5%) and LLD use (2.1 [1, 6–2, 4] vs 1.0%), respectively, in the year after the intervention. Univariate and multivariate analysis showed that a higher blood pressure and cholesterol level, but not the presence of other cardiovascular risk factors, were associated to with a greater percentage use of a BPLD and a LLD. A population survey followed by a letter of intervention to both the patient and GP are effective to improve the use of blood pressure and lipid lowering drugs as a primary prevention in patients with hypertension and hyperlipidemia. Our therapeutic advice however, was followed only in about one of the three subjects with hypertension and one of the four subjects with hyperlipidemia. The levels of blood pressure and plasma total cholesterol are important variables influencing the GP to prescribe a BPLD and/or LLD. [ABSTRACT FROM AUTHOR]