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1.
Nutrients ; 15(8)2023 Apr 11.
Article in English | MEDLINE | ID: covidwho-2324174

ABSTRACT

Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.


Subject(s)
Blood Component Removal , Hyperlipoproteinemia Type II , Humans , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Subtilisin , Proprotein Convertase 9 , Proprotein Convertases/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Cholesterol, LDL , Blood Component Removal/methods
2.
Ann Med ; 55(1): 2199218, 2023 12.
Article in English | MEDLINE | ID: covidwho-2305381

ABSTRACT

Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients. Similarly, in SARS-CoV-2 - infected patients one beneficial mechanism of action of statins may be the amelioration of endothelial dysfunction, which is a major driver of CMD. Apart from statins, lipoprotein apheresis and PCSK9 inhibitors can also improve or even reverse CMD. The potential reversal of CMD by using effective cholesterol-lowering medications during and after COVID-19 infection, especially in hypercholesterolemic COVID-19 patients, is important.KEY MESSAGESCoronary microvascular dysfunction (CMD) is common in patients hospitalized with SARS-CoV-2 infectionThree nonrandomized studies in non-infected patients are showing the beneficial effects of statin treatment on CMDEffective cholesterol-lowering medication during and after SARS-CoV-2 infection, especially in hypercholesterolemic COVID-19 patients, is of great significance.


Subject(s)
Anticholesteremic Agents , COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Proprotein Convertase 9 , COVID-19/complications , Cholesterol, LDL , Microcirculation , SARS-CoV-2 , Anticholesteremic Agents/therapeutic use , Anticholesteremic Agents/pharmacology , Cholesterol
3.
Am J Clin Nutr ; 116(3): 640-652, 2022 09 02.
Article in English | MEDLINE | ID: covidwho-2295372

ABSTRACT

BACKGROUND: Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options. OBJECTIVES: We compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM. METHODS: Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake. RESULTS: The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable. CONCLUSIONS: HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378.


Subject(s)
Diabetes Mellitus, Type 2 , Diet, Ketogenic , Diet, Mediterranean , Prediabetic State , Adolescent , Adult , Blood Glucose , Cholesterol, LDL , Cross-Over Studies , Glycated Hemoglobin/analysis , Humans , Triglycerides , Vegetables
4.
BMJ Open Diabetes Res Care ; 11(1)2023 02.
Article in English | MEDLINE | ID: covidwho-2288527

ABSTRACT

The popularity of teleconsultation during the COVID-19 pandemic enabled increased accessibility for individuals with type 2 diabetes mellitus (T2DM). However, previous studies did not distinguish between synchronous and asynchronous teleconsultation. We evaluated the effectiveness of synchronous teleconsultation for patients with T2DM. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library and Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to July 2021. All included studies were randomized controlled trials of synchronous teleconsultation for adults with T2DM compared with usual care. Reviewers independently extracted data and used the Cochrane tool to evaluate risk of bias. Meta-analyses were conducted using random-effects models. A pooled mean difference for both HbA1c (%) and body mass index (BMI) (kg/m2), systolic blood pressure (SBP) (mm Hg), diastolic blood pressure (DBP) (mm Hg), and low density lipoprotein cholesterol (LDL-cholesterol) (mg/dL) were calculated. Patient-reported outcomes, such as depression, medication adherence, and quality of life, were also assessed. A total of 9807 abstracts were identified and 27 trials were included. Synchronous teleconsultation significantly resulted in greater decrease in HbA1c compared with usual care group (n=8746, 0.35, 95% CI 0.20 to 0.49, I2=73%, p<0.001). No significant effects on BMI (n=699, 0.08 kg/m2, 95% CI -0.54 to 0.69), SBP (n=5512, 1.32 mm Hg, 95% CI -0.09 to 2.73), DBP (n=2898, 0.17 mm Hg, 95% CI -1.18 to 1.52), or LDL-cholesterol (n=5276, 3.21 mg/dL, 95% CI -1.75 to 8.17) were found. The effect of teleconsultation in improving patient-reported outcomes was uncertain. Thus, synchronous teleconsultation could be an alternative to usual care. Systematic review registration is PROSPERO CRD42021267019.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Remote Consultation , Adult , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Quality of Life , Glycated Hemoglobin , Pandemics , Cholesterol, LDL , Randomized Controlled Trials as Topic
5.
Clin Transl Sci ; 16(3): 489-501, 2023 03.
Article in English | MEDLINE | ID: covidwho-2269278

ABSTRACT

Sepsis accounts for one in three hospital deaths. Higher concentrations of high-density lipoprotein cholesterol (HDL-C) are associated with apparent protection from sepsis, suggesting a potential therapeutic role for HDL-C or drugs, such as cholesteryl ester transport protein (CETP) inhibitors that increase HDL-C. However, these beneficial clinical associations might be due to confounding; genetic approaches can address this possibility. We identified 73,406 White adults admitted to Vanderbilt University Medical Center with infection; 11,612 had HDL-C levels, and 12,377 had genotype information from which we constructed polygenic risk scores (PRS) for HDL-C and the effect of CETP on HDL-C. We tested the associations between predictors (measured HDL-C, HDL-C PRS, CETP PRS, and rs1800777) and outcomes: sepsis, septic shock, respiratory failure, and in-hospital death. In unadjusted analyses, lower measured HDL-C concentrations were significantly associated with increased risk of sepsis (p = 2.4 × 10-23 ), septic shock (p = 4.1 × 10-12 ), respiratory failure (p = 2.8 × 10-8 ), and in-hospital death (p = 1.0 × 10-8 ). After adjustment (age, sex, electronic health record length, comorbidity score, LDL-C, triglycerides, and body mass index), these associations were markedly attenuated: sepsis (p = 2.6 × 10-3 ), septic shock (p = 8.1 × 10-3 ), respiratory failure (p = 0.11), and in-hospital death (p = 4.5 × 10-3 ). HDL-C PRS, CETP PRS, and rs1800777 significantly predicted HDL-C (p < 2 × 10-16 ), but none were associated with sepsis outcomes. Concordant findings were observed in 13,254 Black patients hospitalized with infections. Lower measured HDL-C levels were significantly associated with increased risk of sepsis and related outcomes in patients with infection, but a causal relationship is unlikely because no association was found between the HDL-C PRS or the CETP PRS and the risk of adverse sepsis outcomes.


Subject(s)
Sepsis , Shock, Septic , Adult , Humans , Cholesterol, HDL/genetics , Cholesterol, HDL/metabolism , Cholesterol Ester Transfer Proteins/genetics , Cholesterol Ester Transfer Proteins/metabolism , Hospital Mortality , Cholesterol, LDL/metabolism , Sepsis/genetics
6.
Front Public Health ; 11: 1048087, 2023.
Article in English | MEDLINE | ID: covidwho-2257472

ABSTRACT

Objective: To compare the physiological health of Chinese children around the COVID-19 lockdown. Methods: We extracted data on children's anthropometric and laboratory parameters from May to November in both 2019 and 2020 from the Health Checkup Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Overall, 2162 children aged 3~18 years without comorbidities in 2019 and 2646 in 2020 were assessed. Mann Whitney U tests were used to compare differences between the above health indicators before and after COVID-19 outbreak. Quantile regression analyses adjusted for age, sex and body mass index (BMI) were also used in analysis. Chi-square tests and Fisher's exact tests were used for comparing differences of categorical variables. Results: Compared with children examined in 2019 before the outbreak, children in 2020 had a higher median z score of BMI for age (-0.16 vs. -0.31), total cholesterol (TC, 4.34 vs. 4.16 mmol/L), low density lipoprotein cholesterol (LDL-C, 2.48 vs. 2.15 mmol/L), high density lipoprotein cholesterol (HDL-C, 1.45 vs. 1.43 mmol/L) and serum uric acid (290 vs. 282 µmol/L), and a lower hemoglobin (Hb, 134 vs. 133 g/L), triglycerides (TG, 0.70 vs. 0.78 mmol/L) and 25(OH)D (45.8 vs. 52.2 nmol/L), all P < 0.05. No differences were identified for waist height ratio, blood pressure and fasting glucose (both P > 0.05). However, in regression models after adjusting, BMI, TC, LDL-C, blood glucose and sUA were positively correlated with year; while Hb, TG and 25(OH)D were negatively correlated with year (all P < 0.05). Accordingly, children in 2020 had a higher prevalence of overweight/obesity (20.6 vs. 16.7%, P < 0.001), hypercholesterol (16.2%vs. 10.2%, P < 0.001), high LDL-C (10 vs. 2.9%, P < 0.001), hyperuricemia (18.9 vs.15.1%, P = 0.002), vitamin D deficiency (22.6 vs. 8.1%, P < 0.001) and a lower prevalence of high TG (4.3 vs. 2.8%, P = 0.018) compared with children in 2019. Conclusion: In this real-world study, we found that long-term lockdown due to COVID-19 outbreak might cause adverse impact on children's metabolic health, which might increase their future risk of cardiovascular diseases. Thus, parents, health professionals, educationists, and caregivers should pay more attention to children's dietary pattern and lifestyle, especially in this new normal against COVID-19.


Subject(s)
COVID-19 , Lipids , Overweight , Pediatric Obesity , Child , Humans , Cholesterol, LDL , Communicable Disease Control , East Asian People , Lipids/blood , Uric Acid , Child, Preschool , Adolescent , Overweight/epidemiology , Pediatric Obesity/epidemiology
7.
Drugs ; 83(5): 403-427, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2252351

ABSTRACT

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.


Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.


Subject(s)
Berberine , Dyslipidemias , Male , Humans , Adult , Female , Cholesterol, HDL , Cholesterol, LDL , Berberine/adverse effects , Cholesterol , Triglycerides , Lipids , Dyslipidemias/drug therapy , Apolipoproteins , Randomized Controlled Trials as Topic
8.
AIDS Res Hum Retroviruses ; 38(11): 878-880, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2263763

ABSTRACT

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.


Subject(s)
Anti-HIV Agents , Cardiovascular Diseases , HIV Infections , HIV-1 , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Retrospective Studies , Preliminary Data , Cholesterol, LDL , Anti-HIV Agents/therapeutic use
9.
N Engl J Med ; 387(21): 1923-1934, 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2256304

ABSTRACT

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Hypertriglyceridemia , Hypolipidemic Agents , PPAR alpha , Humans , Apolipoprotein C-III/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cholesterol/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/complications , Double-Blind Method , Heart Disease Risk Factors , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/blood , Hyperlipidemias/drug therapy , Hypertriglyceridemia/blood , Hypertriglyceridemia/complications , Hypertriglyceridemia/drug therapy , Risk Factors , Triglycerides/blood , Hypolipidemic Agents/therapeutic use , PPAR alpha/agonists , Cholesterol, HDL/blood
10.
Curr Opin Lipidol ; 34(3): 119-125, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2285765

ABSTRACT

PURPOSE OF REVIEW: Patients with heterozygous familial hypercholesterolemia (HeFH) are at increased risk for COVID-19 cardiovascular complications in the acute phase of the infection. Elevated levels of LDL-C and often lipoprotein(a) are present from birth and lead to endothelial dysfunction, which is aggravated by a direct viral attack of the endothelial cells and their exposure to the toxic levels of circulating proinflammatory and prothrombotic mediators during the hyperinflammatory reaction typical of COVID-19. RECENT FINDINGS: Evidence to date shows the benefit of lipid-lowering therapy in patients with COVID-19. In HeFH patients who are at much higher cardiovascular risk, the focus should, therefore, be on the effective lowering of LDL-C levels, the root cause of the greater cardiovascular vulnerability to COVID-19 infection in these patients. The ongoing use of statins and other lipid-lowering therapies should be encouraged during the ongoing COVID pandemic to mitigate the risk of cardiovascular complications from COVID-19, particularly in HeFH patients. SUMMARY: Epidemiologic registry data show that the incidence of myocardial infarction is increased in SARS-CoV-2-infected HeFH patients. There is a need to study whether the risk for acute cardiovascular events is increased in the long-term and if there are changes in lipid metabolism after SARS-CoV infection(s) in patients with HeFH.


Subject(s)
COVID-19 , Hypercholesterolemia , Hyperlipoproteinemia Type II , Humans , Cholesterol, LDL , Endothelial Cells , COVID-19/complications , SARS-CoV-2 , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/epidemiology , Hypercholesterolemia/complications
11.
J Am Coll Cardiol ; 81(3): 224-234, 2023 01 24.
Article in English | MEDLINE | ID: covidwho-2243693

ABSTRACT

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).


Subject(s)
COVID-19 , Proprotein Convertase 9 , Humans , Interleukin-6 , Cholesterol, LDL , SARS-CoV-2 , Inflammation , Treatment Outcome , Double-Blind Method
12.
PLoS One ; 18(2): e0278083, 2023.
Article in English | MEDLINE | ID: covidwho-2236506

ABSTRACT

Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19 caused by SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2). Last data suggested the possible role of extracellular vesicles in COVID-19 pathogenesis. The aim of the present study was to retrospectively evaluate parameters of cholesterol metabolism and newly identified EVs, exomeres, as possible predictors of fatal outcome of COVID-19 patients infected by the Alpha and the Delta variants of SARS-CoV-2 virus. Blood from 67 patients with severe COVID-19 were collected at the time of admission to the intensive care unit (ICU) and 7 days after admission to the ICU. After 30 days patients were divided into two subgroups according to outcome-34 non-survivors and 33 survivors. This study demonstrated that plasma low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased in non-survivors compared to controls at the time of admission to the ICU. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors infected by the Alpha and the Delta variants compared to survivors at the time of admission to the ICU. We first showed that reduction of exomeres fraction may be critical in fatal outcome of COVID-19.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Cholesterol, LDL , Retrospective Studies
13.
PLoS One ; 17(9): e0273675, 2022.
Article in English | MEDLINE | ID: covidwho-2021932

ABSTRACT

Psychological problems commonly experienced by patients with type 2 diabetes mellitus (T2DM) cause diabetes fatigue conditions that can further worsen the treatment prognosis. We conducted this investigation to determine the effectiveness of a resilience-based Islamic program on diabetes fatigue and health-related quality of life (HRQoL) by measuring the biochemical indicators of T2DM. This was a quasi-experimental study performed from May to August 2021, in which 80 respondents aged 18-64 years diagnosed with T2DM were included through purposive sampling at a male:female sex ratio of 1:1 in the control group and 17:23 in the treatment group. A resilience-based Islamic program (a combination of stress management, mindfulness, prayer, and dhikr (the ritual formula of Sufi brotherhood recited devotionally in praise of Allah and as a means of attaining ecstatic experience)) was implemented in the treatment group for six sessions by blended online and offline interventions. Multidimensional Fatigue Inventory-20 and World Health Organization Quality of Life, Brief Form were used to evaluate diabetes fatigue and HRQoL. Blood tests were performed to measure HbA1c, total antioxidant serum, insulin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels from baseline to 3 months. Statistical analyses were conducted using paired t test, Wilcoxon signed-rank test, independent t test, and Mann-Whitney U test. The resilience-based Islamic program had a beneficial impact on the levels of HbA1c (p < 0.001), lipid profile (triglyceride) (p = 0.011), HDL-c (p = 0.01), LDL-c (p < 0.001), total antioxidant serum (p = 0.001), insulin (p < 0.001), diabetes fatigue (p < 0.05), and HRQoL (p < 0.05) in patients of the treatment group. The results of biochemical tests related to T2DM also indicated a reduction in diabetes fatigue and an increase in HRQoL due to the resilience-based Islamic program. Considering that a patient's resilience to diabetes is an important factor in the management of diabetes fatigue, the resilience-based Islamic program can be applied at public health centers and community levels to increase T2DM resilience.


Subject(s)
Diabetes Mellitus, Type 2 , Quality of Life , Antioxidants , Cholesterol , Cholesterol, HDL , Cholesterol, LDL , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Fatigue/therapy , Female , Glycated Hemoglobin , Humans , Insulin , Male , Triglycerides
14.
Bratisl Lek Listy ; 123(8): 589-593, 2022.
Article in English | MEDLINE | ID: covidwho-1994312

ABSTRACT

OBJECTIVES: Serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol may be associated with a poor prognosis in COVID-19 patients. BACKGROUND: We think it may be essential to understand the role of lipids in the pathophysiology of COVID-19. METHODS: One hundred eighty-nine patients admitted to the emergency department between 20th January and 20th February 2021 and later decided to be hospitalized to an inpatient clinic or intensive care unit were included in the study. The patients were determined to be hospitalized to the inpatient clinic or intensive care unit according to the Turkish Ministry of Health COVID-19 guidelines. A demographic information form was established for each patient. RESULTS: The primary findings we have obtained were as follows: (1) CRP, PCT, D-Dimer levels were found to be high, while Albumin, TC, HDL-c, and LDL-c levels were found to be low in critical type patients; (2) CRP, PCT, and D-Dimer levels were higher in the patients who were intubated compared to those who were not intubated. Albumin and HDL levels were low; (3) DH was found to have a significantly negative relationship with TC and HDL-c, and (4) Sensitivity of LDL-c in predicting mortality was found as 69 % and specificity as 70 %. It was observed that patients with low LDL-c levels had higher mortality rates. CONCLUSION: We think that hypocholesterolaemia may be an indicator of the impending danger. Our study examined COVID-19 in terms of lipid metabolism and offers a different perspective on the disease (Tab. 4, Ref. 23). Text in PDF www.elis.sk Keywords: COVID-19, lipid, mortality.


Subject(s)
COVID-19 , Albumins , Cholesterol, HDL , Cholesterol, LDL , Humans , Severity of Illness Index , Triglycerides
15.
Curr Opin Endocrinol Diabetes Obes ; 29(5): 427-433, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1985176

ABSTRACT

PURPOSE OF REVIEW: The low-density lipoprotein (LDL)-cholesterol level is a weak predictor of developing cardiovascular (CV) disease and can only explain a small proportion of CV risk. It is not used to determine CV risk on either the atherosclerotic cardiovascular disease (ASCVD) calculator in the United States, or the Qrisk3 in the UK.A study in JAMA in 2022 suggested that ' the absolute benefits of statins are modest and may not be strongly mediated through the degree of LDL reduction '. Perhaps it is time to look beyond cholesterol to a different causal model - the 'thrombogenic' model of ASCVD. RECENT FINDINGS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic demonstrated that infectious agents damage the endothelium and the glycocalyx - the glycoprotein layer protecting underlying endothelial cells. There are numerous other conditions leading to this kind of damage, which can trigger thrombus formation, causing strokes and myocardial infarctions.Although these are acute events, they highlight a mechanism for the development of ASCVD which centres on endothelial damage and thrombus formation as both the primary causal mechanism for acute events, and the driver behind progression towards atherosclerotic plaque development. SUMMARY: The cholesterol hypothesis, that a raised LDL is directly causal for ASCVD, does not adequately explain cardiovascular risk in individuals, or populations. An alternative 'thrombogenic' hypothesis is proposed as a more valid causal model.


Subject(s)
Atherosclerosis , COVID-19 , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Cardiovascular Diseases/etiology , Cholesterol , Cholesterol, LDL , Endothelial Cells , Humans , RNA, Viral , Risk Factors , SARS-CoV-2 , United States
16.
PLoS One ; 17(8): e0272000, 2022.
Article in English | MEDLINE | ID: covidwho-1968874

ABSTRACT

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10-1.82, OR = 1.06 CI: 1.02-1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06-1.18, OR = 1.24 CI:1.05-1.48, OR = 1.47 CI:1.19-1.80, OR = 1.52 CI:1.01-2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis.


Subject(s)
COVID-19 , Insulin Resistance , Biomarkers , Blood Glucose/analysis , COVID-19/therapy , Cholesterol, HDL , Cholesterol, LDL , Critical Care Outcomes , Glucose , Humans , Triglycerides
17.
Horm Metab Res ; 54(8): 514-521, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1931525

ABSTRACT

An elevated cholesterol concentration has been suspected to increase the susceptibility for SARS-COV-2 infection. Cholesterol plays a central role in the mechanisms of the SARS-COV-2 infection. In contrast, higher HDL-cholesterol levels seem to be protective. During COVID-19 disease, LDL-cholesterol and HDL-cholesterol appear to be decreased. On the other hand, triglycerides (also in different lipoprotein fractions) were elevated. Lipoprotein(a) may increase during this disease and is most probably responsible for thromboembolic events. This lipoprotein can induce a progression of atherosclerotic lesion formation. The same is suspected for the SARS-COV-2 infection itself. COVID-19 patients are at increased risk of incident cardiovascular diseases, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disorders. An ongoing lipid-lowering therapy, including lipoprotein apheresis, is recommended to be continued during the COVID-19 disease, though the impact of lipid-lowering drugs or the extracorporeal therapy on prognosis should be studied in further investigations.


Subject(s)
COVID-19 , COVID-19/complications , Cholesterol , Cholesterol, HDL , Cholesterol, LDL , Humans , Lipoproteins , Risk Factors , SARS-CoV-2 , Triglycerides
18.
Clin Nutr ESPEN ; 49: 191-196, 2022 06.
Article in English | MEDLINE | ID: covidwho-1889299

ABSTRACT

BACKGROUND: COVID-19 is an infectious disease which caused a pandemic with many diseases and fatalities. This new variant of coronavirus called SARS-CoV-2 and is primarily characterized by respiratory symptoms. There are some data indicating that LDL-cholesterol (LDL-C) as well as HDL-cholesterol (HDL-C) levels are inversely correlated to disease severity and could act as a predictor for disease progression and unfavorable prognosis. However, the results of some other studies do not confirm this. This current study aimed to provide an answer to this question. METHODS: This prospective, single-center study analyzed 367 confirmed COVID-19 patients to find whether there are any differences in plasma lipoproteins between survivors and non-survivors patients or between the patients with a "duration of ≤10 days intensive unit care (ICU) stay" and patients with a "duration of >10 days ICU stay". RESULTS: No association between any lipid/lipoprotein parameter and the severity of COVID-19 could be found but survivors and non-survivors did differ concerning total cholesterol and LDL-C levels. CONCLUSION: Multivariate cox regression analysis could not prove any association between lipids/lipoproteins and severe events in COVID-19 patients. Significantly less non-survivors with COVID-19 were taking atorvastatin than survivors which is consistent with the majority of previous findings.


Subject(s)
COVID-19 , Cholesterol, LDL , Humans , Lipoproteins , Prospective Studies , SARS-CoV-2
19.
J Endocrinol Invest ; 45(9): 1749-1756, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1859188

ABSTRACT

PURPOSE: Our study examined whether telemedicine use in primary care is associated with risk factor assessment and control for patients with diabetes mellitus. METHODS: This was a retrospective, 1:1 propensity score matched cohort study conducted in a primary care network between February 2020 and December 2020. Participants included patients with diabetes mellitus, ages 18 to 75. Exposure of interest was any telemedicine visit. We determined whether hemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) were assessed for each patient. For each risk factor, we also determined whether the risk factor was controlled when they were assessed (i.e., last HbA1c < 8.0%, BP < 130/80 mmHg, LDL-C < 100 mg/dL). RESULTS: After 1:1 propensity score matching, we identified 1,824 patients with diabetes during the study period. Telemedicine use was associated with a lower proportion of patients with all three risk factors assessed (162/912 [18%], versus 408/912 [45%], p < 0.001). However, when individual risk factors were assessed, telemedicine use did not impact risk factor control. When compared with patients with in-person visit only, the odds ratio (OR) for HbA1c < 8% was 1.04 (95% CI 0.74 to 1.46, p = 0.23) for patients with any telemedicine visit. Similarly, the OR for BP < 130/80 mmHg was 1.08 (95% CI 0.85-1.36 p = 0.53), and the OR for LDL-C < 100 mg/dL was 1.14 (95% CI 0.76-1.72, p = 0.52). CONCLUSIONS: Telemedicine use was associated with gaps in risk factor assessment for patients with diabetes during the COVID-19 pandemic, but had limited impact on whether risk factors were controlled.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Diabetes Mellitus , Telemedicine , Adolescent , Adult , Aged , Blood Pressure , COVID-19/epidemiology , Cholesterol, LDL , Cohort Studies , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Glycated Hemoglobin/analysis , Humans , Middle Aged , Pandemics , Primary Health Care , Retrospective Studies , Risk Factors , Young Adult
20.
Front Public Health ; 10: 850191, 2022.
Article in English | MEDLINE | ID: covidwho-1785450

ABSTRACT

Objective: To investigate whether first-trimester fasting plasma glucose (FPG), blood coagulation function and lipid metabolism could predict gestational diabetes mellitus (GDM) risk. Methods: From October 2020 to May 2021, a total of 584 pregnant women who took prenatal care in Shanghai Jiaotong University Affiliated Sixth People's Hospital were chosen as the observation subjects. The clinical information and serum samples of all pregnant women were collected at 10-13 weeks of gestation and the blood coagulation function, fasting blood glucose and lipid profiles of the pregnant women were detected. A 75 g oral glucose tolerance test was performed up to 24-28 weeks of gestation. One hundred forty-two pregnant women with GDM and 442 pregnant women without GDM were detected. Data were expressed by x ± s or median (interquartile range) and were analyzed using student's t-test, Wilcoxon rank sum test and Logistic regression analysis. The area under the curve (AUC) was calculated by receiver operating characteristic curve (ROC) to analyze the predictive values. Results: Compared with non-GDM group, age, pre-pregnancy BMI, FPG, FIB, D-Dimer, FDP, FPG, TC, TG, LDL-C, sdLDL-C, APOB and APOE in GDM group were significantly higher than those in non-GDM group, while PT, INR, APTT and TT were significantly lower than those in non-GDM group. Univariate logistic regression analysis was used to explore the risk factors of GDM. Gestational age, pre-pregnancy BMI, FPG, PT, INR, APTT, FIB, TT, D-Dimer, TC, TG, LDL-C, sdLDL-C, APOB and APOE were all independent predictors of GDM. Multivariatelogistic regression showed that pre-pregnancy BMI, FPG, APTT, TT, TG, LDL-C, sdLDL-C and APOB were risk factors for GDM. The AUC of the established GDM risk prediction model was 0.892 (0.858-0.927), and the sensitivity and specificity were 80.71 and 86.85%, respectively; which were greater than that of pre-pregnancy BMI, FPG, APTT, TT,TG, LDL-C, sdLDL-C, APOB alone, and the difffference was statistically signifificant (P < 0.05). Conclusions: FPG, APTT, TT, TG, LDL-C, sdLDL-C, APOB and pre-pregnancy BMI in early pregnancy has important clinical value for the prediction of GDM, We combined these laboratory indicators and established a GDM risk prediction model, which is conducive to the early identification, intervention and treatment of GDM, so as to reduce the morbidity of maternal and infant complications.


Subject(s)
Diabetes, Gestational , Apolipoproteins B/metabolism , Apolipoproteins E/metabolism , Blood Coagulation , Blood Glucose/analysis , Blood Glucose/metabolism , Body Mass Index , Cholesterol, LDL/metabolism , Diabetes, Gestational/diagnosis , Early Diagnosis , Female , Glycolipids , Humans , Lipid Metabolism , Pregnancy
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