Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia

Braamskamp, Marjet J. A. M.; Langslet, Gisle; McCrindle, Brian W.; Cassiman, David; Francis, Gordon A.; Gagné, Claude; Gaudet, Daniel; Morrison, Katherine M.; Wiegman, Albert; Turner, Traci; Miller, Elinor; Kusters, D. Meeike; Raichlen, Joel S.; Martín, Paul; Stein, Evan A.; Kastelein, John J.P.; Hutten, Barbara A.

doi:10.1161/circulationaha.116.025158

Cited by 90 publications

(29 citation statements)

References 19 publications

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“…IMT is a reliable marker of early atherosclerosis, is an established risk factor for incident cardiovascular acute events, and is used to evaluate the global cardiovascular risk [ 32 ]. Carotid IMT has been frequently monitored in interventional studies to evaluate the efficacy of several drugs in terms of cardiovascular protection [ 33 – 35 ]. IMT was inversely and strongly associated with wall shear stress [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy

Irace

Casciaro

Scavelli

et al. 2018

Cardiovasc Diabetol

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BackgroundCardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function.ObjectiveWe designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness.MethodsThe study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software.ResultsBlood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS).ConclusionsThis study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

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Section: Discussionmentioning

confidence: 99%

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy

Irace

Casciaro

Scavelli

et al. 2018

Cardiovasc Diabetol

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“…This work provides another argument for introducing screening programs because, even in children with no signi cant morphological changes, arterial wall function can be already impaired. Diagnosis of subclinical arterial wall stiffening might improve risk strati cation and clinical management in FH patients [13,19].…”

Section: Discussionmentioning

confidence: 99%

“Apple does not fall far from the tree” – subclinical atherosclerosis in children with familial hypercholesterolemia.

Podgórski

Szatko

Stańczyk

et al. 2020

Preprint

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Background: Familial hypercholesterolemia (FH) increases the risk of atherosclerosis in children and adults. Atherosclerotic cardiovascular disease in young patients FH is usually subclinical but recognition of children with more pronounced changes is crucial for adjusting effective management. Aim of this research was to use ultrasonography with two-dimensional speckle tracking (2DST) and tonometry to evaluate atherosclerotic changes in patients with FH (parents and their offspring).Methods: Applanation tonometry and carotid arteries sonography with evaluation of the intima-media complex thickness (IMCT) and application of the 2DST were performed in 20 families with FH (20 parents and 29 children). The same size control group (age and sex matched) was included. Results were compared between peers and between generations together with the correlation analysis.Results: Adults with FH, in comparison with healthy peers, presented significantly more atherosclerotic plaques (9 vs. 2, p=0.0230), had significantly thicker IMC (0.84±0.19 vs. 0.56±0.06 mm, p<0.0001) and had stiffer arterial wall (for stain: 6.25±2.3 vs. 8.15±2.46, p=0.0103). In children from both groups there were no atherosclerotic plaques and IMCT did not differ significantly (0.42±0.07 vs. 0.39±0.04, p=0.1722). However, children with FH had significantly stiffer arterial wall according to 2DST (for strain: 9.22±3.4 vs. 11.93±3.11, p=0.0057) and tonometry (for the pulse wave velocity: 4.5±0.64 vs.3.96±0.62, p=0.0047). These parameters correlated with atherosclerosis surrogates in their parents (p<0.001) but were not significantly affected by presence of presumed pathogenic gene variant.Conclusions: Children with FH presented subclinical atherosclerosis manifested as decreased arterial wall elasticity. Degree of stiffening was associated with advancement of atherosclerosis in their parents but did not present significant association with gene variants. Sonography with application of 2DST seems to be a good candidate for comprehensive evaluation of atherosclerosis in families with FH.

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“…A mean LDL-C reduction of 41% after 2 years of treatment with rosuvastatin was associated with a significant reduction in the progression of carotid atherosclerosis. 77 Moreover, the 10-year follow-up of children with mean age 12 years old treated with pravastatin during 2 years showed that the statin treatment initiated in childhood normalizes the carotid intima media thickness in the young adults (mean age 24 years old). 78 Recently, the 20-year follow-up of this population has been published comparing the incidence of ASCVD among these patients that started statins since childhood and their affected parents, assuming that parents started statin treatment later in life.…”

Section: Treatment Of Children Living With Fh (Table 2)mentioning

confidence: 99%

<p>Barriers to Early Diagnosis and Treatment of Familial Hypercholesterolemia: Current Perspectives on Improving Patient Care</p>

Alonso¹,

Isla²,

Muñiz-Grijalvo³

et al. 2020

VHRM

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Familial hypercholesterolemia (FH) is a frequent disorder associated with premature atherosclerotic cardiovascular disease. Different clinical diagnosis criteria are available, and cost of genetic testing has been reduced in the last years; however, most cases are not diagnosed worldwide. Patients with FH are at high cardiovascular risk and the risk can be reduced with lifelong lifestyle and pharmacological treatment. Statins and ezetimibe are available as generic drugs in most countries reducing the cost of treatment. However, the use of high-intensity statins combined with ezetimibe and PCSK9 inhibitors, if necessary, is low for different reasons that contribute to a high number of patients not reaching LDL-C targets according to guidelines. On the other hand, cardiovascular risk varies greatly in families with FH; therefore, risk stratification strategies including cardiovascular imaging is another element to consider for improving care and management of FH. There are numerous barriers depending on the awareness, knowledge, perception of risk, management and care of patients living with FH that impact in the diagnosis and treatment of the disorder. In this contemporary review, we analyze different barriers in the diagnosis and care of patients to improve patients' care and prevention of atherosclerotic cardiovascular disease and describe recent advances and strategies to improve the gaps in the care of FH, including global collaboration and advocacy.

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Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children With Heterozygous Familial Hypercholesterolemia

Abstract: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675.

Cited by 90 publications

References 19 publications

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy

Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy

“Apple does not fall far from the tree” – subclinical atherosclerosis in children with familial hypercholesterolemia.

<p>Barriers to Early Diagnosis and Treatment of Familial Hypercholesterolemia: Current Perspectives on Improving Patient Care</p>

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