Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy

ObjectiveA common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy.DesignProspective study of GHD patients evaluated before and during short- (1 year,n=100) and long-term (5 years,n=50) rhGH therapy.MethodsEffects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant.ResultsThe different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed.ConclusionThe functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.

Download Full-text

Treatment of familial hypercholesterolaemia in children and adolescents in the last three decades

Cardiology in the Young ◽

10.1017/s1047951113000528 ◽

2013 ◽

Vol 24 (3) ◽

pp. 437-441 ◽

Cited By ~ 9

Author(s):

Avishay Elis ◽

Rong Zhou ◽

Evan A. Stein

Keyword(s):

Children And Adolescents ◽

Familial Hypercholesterolaemia ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Cholesterol Levels ◽

Heterozygous Familial Hypercholesterolaemia

AbstractBackground:This study evaluated the effectiveness of long-term intensive lipid-lowering therapy in children and adolescents with familial hypercholesterolaemia.Methods:The charts of 89 children and adolescents with heterozygous familial hypercholesterolaemia among ∼1000 patients treated from 1974 to 2008 were reviewed. Familial hypercholesterolaemia was defined as low-density lipoprotein cholesterol level >90th percentile in individuals with a history of familial hypercholesterolaemia.Results:Of the 89 patients, 51% were male; the mean age at diagnosis was 8 ± 4 years, and the mean follow-up was 13 ± 8 years. Baseline and most recent low-density lipoprotein cholesterol levels (mg/dl) under treatment were 250 ± 50 and 142 ± 49, respectively, reduced 43% from baseline (p < 0.0001). At the most recent visit, 39 patients received statin monotherapy, mainly atorvastatin or rosuvastatin, and 50 (56%) patients received combination therapy, mainly vytorin or rosuvastain/ezetimibe, 15 patients were >30 years of age, and none developed symptomatic cardiovascular disease or needed revascularisation.Conclusions:Long-term statin-based therapy can reduce low-density lipoprotein cholesterol levels in most children and adolescents with heterozygous familial hypercholesterolaemia and decrease cardiovascular risk significantly.

Download Full-text

Karate Training Improves Metabolic Health in Overweight and Obese Adolescents: A Randomized Clinical Trial

Pediatric Exercise Science ◽

10.1123/pes.2020-0193 ◽

2021 ◽

pp. 1-11

Author(s):

Fabricio de Souza ◽

Luciano Acordi da Silva ◽

Gisele Santinoni Ferreira ◽

Márcia Mendonça Marcos de Souza ◽

Franciane Bobinski ◽

...

Keyword(s):

Oxidative Stress ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Overweight And Obesity ◽

Lipoprotein Cholesterol ◽

Psychological Interventions ◽

Long Term Effects ◽

Low Density Lipoprotein Cholesterol ◽

Stress Markers

Purpose: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Method: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation. Results: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention. Conclusion: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.

Download Full-text

Abstract 14430: Effect Modification of Statin Therapy on the Relationship of Low-density Lipoprotein Cholesterol With Incident CKD in Us Veterans

Circulation ◽

10.1161/circ.142.suppl_3.14430 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jui-Ting Hsiung ◽

Maria Marroquin ◽

Kamyar Kalantar-Zadeh

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Us Veterans ◽

The Impact ◽

Statin Use

Background: Studies suggests that in the general population, hyperlipidemia may confer higher risk of developing chronic kidney disease (CKD). But, there is conflicting data as to whether statins can protect renal function or slow renal degradation. We sought to examine the impact of statins on the association of low-density lipoprotein cholesterol (LDL) and risk of incident CKD. Methods: Our cohort included 1,439,756 US veterans without chronic kidney disease (CKD), but with LDL measured between 2004-2006, who were followed until 2014. Incident CKD was defined as over 3 estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.73m 2 at least 90 days apart. Patients with a statin prescription at the time of LDL measurement were identified. Cox models were used to estimate the associations between LDL with incident CKD. Model adjustments include demographics, comorbidities, smoking status, prescription of fibrate or niacin, body mass index, albumin, high-density lipoprotein cholesterol, and triglycerides. Results: The cohort included 5% females, 16% African Americans, 26% diabetics, and 30% statin-users, with a mean age of 60±13 years. The median [IQR] of LDL and eGFR were 109 [88,133] mg/dL and 83 [72,94] mL/min/1.73m 2 , respectively. A J-shaped association between LDL and incident CKD were observed in both those on statin and not on a statin after adjustment. Low LDL (<70 mg/dL) was associated with a higher risk of incident CKD compared to the reference (LDL 70-<100 mg/dL) regardless of statin use. High LDL ≥160 mg/dL was associated with the highest of risks of incident CKD (HR: 1.08, 95% CI: 1.04, 1.13, and HR: 1.10, 95% CI: 1.07, 1.12, for statin use and no statin use, respectively). Conclusion: Both high and low LDL were associated with higher incident CKD risk independent of statin use in this US veteran cohort. Further studies are needed to understand how to manage cardiovascular disease risk by lowering LDL while simultaneously reducing risk of CKD.

Download Full-text

Abstract P018: Calibration of Analytes Over Twenty-Five Years in the Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.129.suppl_1.p018 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Christina M Parrinello ◽

Morgan E Grams ◽

David Couper ◽

Christie M Ballantyne ◽

Ron C Hoogeveen ◽

...

Keyword(s):

Uric Acid ◽

Troponin T ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

High Sensitivity ◽

Lipoprotein Cholesterol ◽

Gamma Glutamyl Transpeptidase ◽

Deming Regression ◽

The Impact ◽

Over Time

Background: Comparability of laboratory measures over time is important for studies of disease prevalence and progression. While a small amount of bias may seem negligible on an individual level, it can result in substantial misclassification of disease in the population. We conducted a calibration study of important biomarkers across five study visits (25 years) in ARIC. Methods: We re-measured 15 analytes in 200 blood samples to calibrate original measurements at each time point using Bland-Altman plots and Deming regression. We also assessed the impact of calibration on the prevalence of chronic kidney disease (CKD), defined by estimated glomerular filtration rate using creatinine (eGFRcr), and on trends over time. Results: Assays in samples frozen 12-27 years were highly correlated with original values (median r=0.95) after removing outliers (median 4% of values). The range of bias (% difference in means) across visits for each original analyte compared to its reference were: creatinine: 13-49%; uric acid: 3-24%; C-reactive protein: 3-9%; total cholesterol: 1-6%; high density lipoprotein cholesterol: 4-8% (but new methods differed); low density lipoprotein cholesterol: 1-5%; triglycerides: 2-4%; glucose: 1-4%; N-terminal prohormone of brain natriuretic peptide: 2-12%; high sensitivity cardiac troponin T: 1-9%; alanine transaminase (ALT): 21%; aspartate transaminase (AST): 17%; gamma glutamyl transpeptidase: 0.2%; ß2-microglobulin: 1%; beta-trace protein: 13%. Four analytes met calibration criteria: creatinine, uric acid, ALT and AST. The impact on CKD prevalence was substantial and similar to previous statistical calibration (22% uncalibrated, 1.9% previously and 1.3% current laboratory calibration). Trends in eGFRcr over time were better aligned after calibration ( Figure ). Conclusions: Repeat assay of samples shows high correlation with original values. Calibration enables application of absolute cutoffs (required for defining CKD and other conditions) and improves longitudinal analyses.

Download Full-text

Age at period cessation and trajectories of cardiovascular risk factors across mid and later life

Heart ◽

10.1136/heartjnl-2019-315754 ◽

2020 ◽

Vol 106 (7) ◽

pp. 499-505 ◽

Cited By ~ 5

Author(s):

Linda Marie O'Keeffe ◽

Diana Kuh ◽

Abigail Fraser ◽

Laura D Howe ◽

Debbie Lawlor ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Later Life ◽

Glycated Haemoglobin ◽

Lipoprotein Cholesterol ◽

The Impact

ObjectiveTo examine the association between age at period cessation and trajectories of anthropometry, blood pressure, lipids and glycated haemoglobin (HbA1c) from midlife to age 69 years.MethodsWe used data from the UK Medical Research Council National Survey of Health and Development to examine the association between age at period cessation and trajectories of systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC) from 36 to 69 years and trajectories of triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and HbA1c from 53 to 69 years.ResultsWe found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-C and HDL-C from 53 to 69 years and trajectories of SBP or DBP from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HbA1c, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null value.ConclusionHow and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impact over the long term is small.

Download Full-text

Low‐Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events

Journal of the American Heart Association ◽

10.1161/jaha.119.016318 ◽

2020 ◽

Vol 9 (23) ◽

Author(s):

Peter Willeit ◽

Calvin Yeang ◽

Patrick M. Moriarty ◽

Lena Tschiderer ◽

Stephen A. Varvel ◽

...

Keyword(s):

Cardiovascular Disease ◽

Clinical Care ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cholesterol Content ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Lipoprotein A ◽

The Impact

Background Conventional "low‐density lipoprotein cholesterol (LDL‐C)" assays measure cholesterol content in both low‐density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of “LDL‐C” and corrected LDL‐C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline‐recommended LDL‐C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from “LDL‐C” to obtain corrected LDL‐C values (LDL‐C corr30 ). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual‐patient‐data meta‐analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow‐up). When comparing top versus bottom quartiles, the multivariable‐adjusted hazard ratio for cardiovascular disease was significant for “LDL‐C” (1.17; 95% CI, 1.05–1.31; P =0.005) but not for LDL‐C corr30 (1.07; 95% CI, 0.93–1.22; P =0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline‐recommended LDL‐C categories when using LDL‐C corr30 was assessed. In “LDL‐C” categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL‐C categories when LDL‐C corr30 was used: 30.2% (30.0%–30.4%), 35.1% (34.9%–35.4%), 32.9% (32.6%–33.1%), and 41.1% (40.0%–42.2%), respectively. Conclusions “ LDL‐C” was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL‐C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.

Download Full-text

Real-world use of PCSK9 inhibitors: A single-center experience

Journal of International Medical Research ◽

10.1177/0300060518800595 ◽

2018 ◽

Vol 47 (1) ◽

pp. 265-270 ◽

Cited By ~ 1

Author(s):

Sinan Sarsam ◽

Abeer Berry ◽

George Degheim ◽

Robby Singh ◽

Marcel Zughaib

Keyword(s):

Cardiovascular Disease ◽

Lipid Profile ◽

Real World ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Atherosclerotic Cardiovascular Disease ◽

Pcsk9 Inhibitors ◽

Pcsk9 Inhibitor ◽

The Impact

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

Download Full-text

Long-term Low-Density Lipoprotein Cholesterol–Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia

JAMA Cardiology ◽

10.1001/jamacardio.2017.0747 ◽

2017 ◽

Vol 2 (6) ◽

pp. 598 ◽

Cited By ~ 80

Author(s):

Michael J. Koren ◽

Marc S. Sabatine ◽

Robert P. Giugliano ◽

Gisle Langslet ◽

Stephen D. Wiviott ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Cholesterol Lowering

Download Full-text

Impact of Recreational Sports Activities on Metabolic Syndrome Components in Adolescents

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17010143 ◽

2019 ◽

Vol 17 (1) ◽

pp. 143 ◽

Cited By ~ 1

Author(s):

Fernanda Faria ◽

Cheryl Howe ◽

Ricardo Faria ◽

Alynne Andaki ◽

João Carlos Marins ◽

...

Keyword(s):

Metabolic Syndrome ◽

Intervention Program ◽

Vigorous Physical Activity ◽

Low Density Lipoprotein ◽

Intervention Group ◽

Density Lipoprotein ◽

Recreational Sports ◽

Fat Percentage ◽

The Impact ◽

Sports Activities

We investigated the impact of a sports activities program on metabolic syndrome (MetS) components and pre-MetS among adolescents. Blood samples, blood pressure, weight, height, body mass index, waist circumference, body fat percentage, frequency of food consumption, daily time in moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB) of 92 male adolescents aged 14–18 years (16.07 ± 0.93) were evaluated. From this initial sample, 36 participants (39.1%) were diagnosed with pre-MetS or MetS and were invited to participate in the intervention program. Twelve individuals diagnosed with pre-MetS or MetS agreed to participate in a recreational sports activities program lasting 14 weeks. The pre- and post-sport program comparison showed a reduction in total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL), and an increase in HDL and MVPA time in the intervention group. Sports activities accounted for 42% of the MVPA daily recommendation, and at the end of the intervention period, only seven subjects maintained a positive diagnosis for pre-MetS or MetS. This study showed that recreational sports activities had a significant impact on the lipid profile.

Download Full-text