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Journal of Atherosclerosis and... Aug 2021Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function... (Review)
Review
Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.
Topics: Disease Management; Humans; Hypercholesterolemia; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Phytosterols
PubMed: 33907061
DOI: 10.5551/jat.RV17052 -
Frontiers in Immunology 2021Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However,... (Comparative Study)
Comparative Study Randomized Controlled Trial
The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.
Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 ( = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of and , and the relative abundance of , , and , and decreased unclassified In the oat group, abundance was negatively correlated with LDL-C ( = 0.01, = -0.31) and, TC and LDL-C were negatively correlated to ( = 0.02, = -0.29; = 0.03, = -0.27, respectively). , , and were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid ( = 0.02, = -0.25) and total triglyceride (TG) was positively correlated to isovaleric acid ( = 0.03, = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. , , , and , and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.
Topics: Adult; Avena; Bacteria; Beijing; Biomarkers; Dysbiosis; Edible Grain; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Oryza; Prebiotics; Single-Blind Method; Time Factors; Treatment Outcome
PubMed: 34956218
DOI: 10.3389/fimmu.2021.787797 -
Nutrition, Metabolism, and... Sep 2021The DASH diet was designed for helping control of blood pressure but, fortunately, it can also be prescribed for many other chronic conditions. The current study... (Meta-Analysis)
Meta-Analysis
The effects of the Dietary Approaches to Stop Hypertension (DASH) diet on metabolic risk factors in patients with chronic disease: A systematic review and meta-analysis of randomized controlled trials.
AIMS
The DASH diet was designed for helping control of blood pressure but, fortunately, it can also be prescribed for many other chronic conditions. The current study intended to assess the potential effects of DASH diet on metabolic risk factors in patients with chronic disease.
DATA SYNTHESIS
We carried out a systematic literature search for RCTs from inception until July 2020. A total of 54 clinical trials were included in the final analysis. Compared to control groups, a significant lower effect of the DASH diet was noted for body weight (-1.59 kg; p < 0.001), BMI (-0.64 kg/m; p < 0.001), and WC (-1.93 cm; p < 0.001) as well as for SBP (-3.94 mmHg; p < 0.001) and DBP (-2.44 mmHg; P < 0.001). The DASH diet significantly decreased TC (-5.12 mg/dl; p = 0.008) and LDL-C levels (-3.53 mg/dl; p = 0.041), but not HDL-C (0.30 mg/dl; p = 0.510), TG (-4.22 mg/dl; p = 0.067), and VLDL-C (-2.16 mg/dl; p = 0.062). No significant effect of the DASH diet was noted for blood glucose (-0.38 mg/dl; p = 0.216), insulin (-0.03 μIU/mL; p = 0.817), HOMA-IR (-0.15; p = 0.132), and CRP (-0.33 mg/l; p = 0.173).
CONCLUSIONS
The DASH diet is a feasible approach to weight loss and to control blood pressure and hypercholesterolemia.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiometabolic Risk Factors; Cholesterol; Dietary Approaches To Stop Hypertension; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Obesity; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Weight Loss; Young Adult
PubMed: 34353704
DOI: 10.1016/j.numecd.2021.05.030 -
Hypertension (Dallas, Tex. : 1979) Aug 2021Current guidelines published by the American Heart Association and the American College of Cardiology broadly recommend lifestyle approaches to prevent and treat...
Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How?: A Scientific Statement From the American Heart Association.
Current guidelines published by the American Heart Association and the American College of Cardiology broadly recommend lifestyle approaches to prevent and treat elevated blood pressure and cholesterol. For patients with mildly or moderately elevated blood pressure and blood cholesterol, lifestyle-only approaches are the first line of therapy. The purpose of this scientific statement is to: (1) highlight the mild-moderate-risk patient groups indicated for lifestyle-only treatment for elevated blood pressure or cholesterol; (2) describe recommendations, average effects, and additional considerations when prescribing lifestyle treatment with physical activity; and (3) provide guidance and resources for clinicians to assess, prescribe, counsel, and refer to support increased physical activity in their patients. An estimated 21% and 28% to 37% of US adults, respectively, have mild-moderate-risk blood pressure and cholesterol and should receive lifestyle-only as first-line treatment. Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes. Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol.
Topics: American Heart Association; Exercise; Humans; Hypercholesterolemia; Hypertension; Life Style; United States
PubMed: 34074137
DOI: 10.1161/HYP.0000000000000196 -
Current Opinion in Lipidology Apr 2020This review summarizes the current knowledge regarding autosomal recessive hypercholesterolemia (ARH) and provides new insight into the natural history and therapeutic... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the current knowledge regarding autosomal recessive hypercholesterolemia (ARH) and provides new insight into the natural history and therapeutic management of this lipid disorder.
RECENT FINDINGS
Novel homozygous and compound heterozygous ARH-causing mutations have been reported in the literature, to date. The long-term follow-up of a cohort of ARH patients demonstrated that, despite intensive treatment with conventional lipid-lowering therapies, their low-density lipoprotein (LDL) cholesterol levels remain far from target and this translates into a poor cardiovascular prognosis. ARH is also associated with increased risk of developing aortic valve stenosis. However, lomitapide, a microsomal triglyceride transfers protein inhibitor, may represent a new opportunity for the effective treatment of ARH.
SUMMARY
ARH is an ultrarare disorder of LDL metabolism caused by mutations in the LDLRAP1 gene. It is inherited as a recessive trait and causative mutations, though heterogeneous, are all predicted to be loss-of-function. Recent investigations have demonstrated that ARH can be considered a phenocopy of homozygous familial hypercholesterolemia, where the risk of atherosclerotic cardiovascular diseases and aortic valve stenosis remains elevated despite conventional therapies. The combination of lomitapide with the conventional LDL-C-lowering medications appears to be a promising approach to treat this condition.
Topics: Animals; Anticholesteremic Agents; Benzimidazoles; Humans; Hypercholesterolemia; Lipid Metabolism; Lipoproteins, LDL; Mutation; Hyperlipoproteinemia Type III
PubMed: 32011344
DOI: 10.1097/MOL.0000000000000664 -
Herz Sep 2020The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population.
METHODS
The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model.
RESULTS
The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events.
CONCLUSION
Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.
Topics: Atorvastatin; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome
PubMed: 30483816
DOI: 10.1007/s00059-018-4767-2 -
JAMA Pediatrics Mar 2024Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation.
OBJECTIVE
To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH.
DESIGN, SETTING, AND PARTICIPANTS
This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period.
INTERVENTIONS
Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if ≥50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period.
MAIN OUTCOMES AND MEASURES
The primary end point was percent change in LDL-C from baseline to week 24 in each cohort.
RESULTS
Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was -43.3% (97.5% CI, -56.0 to -30.7; P < .001) Q2W and -33.8% (97.5% CI, -46.4 to -21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab. Two patients receiving alirocumab Q4W experienced adverse events leading to discontinuation. No significant difference in adverse event incidence was observed between treatment groups. Open-label period findings were consistent with the double-blind period.
CONCLUSIONS AND RELEVANCE
The findings in this study indicate that alirocumab Q2W or Q4W significantly may be useful for reducing LDL-C and other lipid parameters and be well tolerated in pediatric patients with HeFH inadequately controlled with statins.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03510884.
Topics: Humans; Female; Child; Male; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antibodies, Monoclonal; Treatment Outcome; Hyperlipoproteinemia Type II; Hypercholesterolemia; Double-Blind Method; Anticholesteremic Agents; Antibodies, Monoclonal, Humanized
PubMed: 38315470
DOI: 10.1001/jamapediatrics.2023.6477 -
Revista Da Associacao Medica Brasileira... Dec 2019
Topics: Brazil; Cardiovascular Diseases; Humans; Hypercholesterolemia; Hypertension; Hypertriglyceridemia; Risk Factors
PubMed: 31994618
DOI: 10.1590/1806-9282.65.12.1421 -
Ageing Research Reviews Jan 2024Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly... (Review)
Review
Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly prevalent in the population. Besides being an important causative factor of cardiovascular diseases, FH has been considered an early risk factor for Alzheimer's disease. Cognitive and emotional behavioral impairments in LDL receptor knockout (LDLr) mice are associated with neuroinflammation, blood-brain barrier dysfunction, impaired neurogenesis, brain oxidative stress, and mitochondrial dysfunction. Notably, today, LDLr mice, a widely used animal model for studying cardiovascular diseases and atherosclerosis, are also considered an interesting tool for studying dementia. Here, we reviewed the main findings in LDLr mice regarding the relationship between FH and brain dysfunctions and dementia development.
Topics: Humans; Animals; Mice; Hypercholesterolemia; Cardiovascular Diseases; Risk Factors; Hyperlipoproteinemia Type II; Brain; Cognition; Alzheimer Disease; Heart Disease Risk Factors
PubMed: 38056504
DOI: 10.1016/j.arr.2023.102149 -
Current Cardiology Reports Sep 2023Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a central role in the metabolism of LDL receptors and mainly acts in the liver. However, there are... (Review)
Review
PURPOSE OF REVIEW
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a central role in the metabolism of LDL receptors and mainly acts in the liver. However, there are accumulating data that PCSK9 involves in several functions in different organs beyond the liver. Herein we aimed to summarize the effects of PCSK9 in tissues other than the liver.
RECENT FINDINGS
PCSK9 has crucial roles in heart, brain and kidney in addition to the cholesterol metabolism. Targeting PCSK9 for the treatment of hypercholesterolemia is effective in the prevention from cardiovascular diseases and PCSK9 inhibitors are getting to be administered in more cases. Therefore understanding the effects of PCSK9 in other tissues gained importance in the use of PCSK9 inhibitors era. PCSK9 participates in cardiac, renal, and neurologic functions however, current literature reveals that use of PSCSK9 inhibitors have beneficial or neutral effects on these organs. Inhibition of PCSK9 is assigned to be associated with new onset diabetes in experimental studies whereas real world data with PCSK9 inhibitors established no relationship between PCSK9 inhibitors and new onset diabetes. PCSK9 might be used as a target for the treatment of nephrotic syndrome and heart failure in the future.
Topics: Humans; Proprotein Convertase 9; PCSK9 Inhibitors; Hypercholesterolemia; Kidney
PubMed: 37428313
DOI: 10.1007/s11886-023-01918-2