The Lipid-Lowering Effects of 3-Hydroxy-3-Methylglutaric Acid and Bile Acid Drainage in WHHL Rabbits

1984 ◽  
Vol 67 (4) ◽  
pp. 439-444 ◽  
Author(s):  
J. L. M. Van Niekerk ◽  
Th. Hendriks ◽  
J. A. Gevers Leuven ◽  
L. Havekes ◽  
H. H. M. De Boer

1. The effect of 3-hydroxy-3-methylglutaric acid (HMG) on serum cholesterol levels was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. 2. Oral administration of HMG resulted in a reduction of serum cholesterol by 39%. 3. Bile acid drainage, by means of either cholestyramine medication or partial ileal bypass (PIB) surgery, also led to significant reductions in circulating cholesterol, by 35 and 59% respectively. 4. Intraperitoneal injection of HMG after PIB surgery further reduced serum cholesterol by 35%. 5. Fibroblasts from the WHHL rabbits did not show high-affinity binding, uptake or degradation of 125I-labelled low density lipoprotein (LDL). 6. The working mechanism of these lipid-lowering therapies in WHHL rabbits is discussed in relation to recent literature. 7. The significant reductions in circulating cholesterol induced by HMG warrant further investigation into the use of this compound in the management of familial hypercholesterolaemia.

1998 ◽  
pp. 141-145 ◽  
Author(s):  
G Michalopoulou ◽  
M Alevizaki ◽  
G Piperingos ◽  
D Mitsibounas ◽  
E Mantzos ◽  
...  

OBJECTIVE: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('high-normal' TSH compared with 'low-normal' TSH). DESIGN AND METHODS: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 microU/ml) as well as those with 'low-normal' TSH (0.40-1.99 microU/ml) were randomly assigned to receive either 25 or 50 microg T4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 microg T4 respectively and groups C and D (high-normal TSH) received 25 and 50 microg T4 respectively. Serum T4, tri-iodothyronine (T3), TSH, free thyroxine index, resin T3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. RESULTS: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77+/-0.55, after: 1.41+/-0.85 microU/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. CONCLUSIONS: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.


2013 ◽  
Vol 24 (3) ◽  
pp. 437-441 ◽  
Author(s):  
Avishay Elis ◽  
Rong Zhou ◽  
Evan A. Stein

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.


2018 ◽  
Vol 17 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Laila A Hopstock ◽  
Anne Elise Eggen ◽  
Maja-Lisa Løchen ◽  
Ellisiv B Mathiesen ◽  
Inger Njølstad ◽  
...  

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.


Cholesterol ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
V. A. Korneva ◽  
T. Yu. Kuznetsova ◽  
T. Yu. Bogoslovskaya ◽  
D. S. Polyakov ◽  
V. B. Vasilyev ◽  
...  

Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable.


1983 ◽  
Vol 21 (19) ◽  
pp. 75-76

Bezafibrate (Bezalip - MCP), an analogue of clofibrate (Atromid-S), has been marketed in the UK for two years. Like clofibrate 1 it lowers both triglyceride and total cholesterol levels in plasma. The reduction is usually in low-density lipoprotein (LDL) cholesterol, whilst high-density lipoprotein (HDL) cholesterol rises. Like other lipid-lowering drugs, it should be used only where appropriate dietary measures have failed and where the hyperlipidaemia poses a significant risk.2


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Erin M Delker ◽  
Estela Blanco ◽  
Patricia East ◽  
Raquel Burrows ◽  
Jorge Delva ◽  
...  

Introduction: In a Chilean sample, adolescents’ CVD risk factors were associated with perceived neighborhood crime. To determine if this effect was sustained, we examined associations between adolescents’ perceived neighborhood crime and their serum cholesterol levels in young adulthood. Neighborhood stress has been cross-sectionally related to dyslipidemia in previous studies. Hypothesis: (1) Higher levels of perceived crime will be associated with higher low-density lipoprotein (LDL) cholesterol and lower high-density lipoprotein (HDL). (2) Sex will modify this association. Methods: Data were from adolescent (x =14 yrs) and young adult waves (x =22 yrs) of the Santiago Longitudinal Study (N=645). Perceived neighborhood crime was measured using three scale items about neighborhood drug use, muggings, burglaries and assaults. Crime was analyzed as a continuous and categorical variable. Fasting HDL and LDL cholesterol (mg/dL) were measured at 22 yrs. Associations between crime and HDL and LDL were analyzed by linear regression, adjusting for sex, age and SES. Effect modification by sex was tested with sex*crime interaction. Results: Participants were low-middle income and 55% female. Females perceived slightly more crime than males (F: x =9.1 M: x =8.8, p=0.30). There was a significant sex*crime interaction for HDL (p=0.03) and LDL (p=0.01). Among males, average HDL and LDL were 100±32 and 41±12; crime did not relate to either outcome. Among females, average HDL and LDL were 100±28 and 46±14; neighborhood crime was negatively associated with HDL and positively associated with LDL. For example, females reporting the most crime had, on average, 7.5 mm/dL lower HDL and 12.8 mm/dL higher LDL than females reporting the least amount of crime (Fig. 1). Conclusions: Perceived crime was prospectively associated with worse lipid profiles among females but not males. A sex-specific stress mechanism may be operating. Further study of the physiologic and behavioral mechanisms contributing to these findings is needed.


1995 ◽  
Vol 10 (7) ◽  
pp. 352-354 ◽  
Author(s):  
I Modai ◽  
A Valevski ◽  
L Kikinzon ◽  
Z Jerushalmy ◽  
A Weizman

SummaryIt has been suggested that low serum cholesterol interferes with brain serotonergic functioning, which results in increased suicidal and aggressive tendencies. To test this hypothesis we investigated the relationship between serum cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride levels, and serotonin uptake by blood platelets in 17 healthy men aged 39.5 ± 10.2 years. Platelet serotonin uptake and serum lipids were assayed concomitantly for each individual. Serum cholesterol levels and other serum lipid levels did not correlate with serotonin uptake by platelets at the concentration of 2 × 10−5 M (a concentration within the maximal uptake capacity range). The results indicate no influence of cholesterol on serotonin uptake, as opposed to some investigators who suggested that high risk of suicide and aggressiveness in hypocholesterolemic individuals is related to impaired serotonin transport.


Author(s):  
N. S. Nurmohamed ◽  
E. S. G. Stroes

AbstractLipid-driven cardiovascular disease (CVD) risk is caused by atherogenic apolipoprotein B (apoB) particles containing low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) [Lp(a)] and resembles a large and modifiable proportion of the total CVD risk. While a surplus of novel lipid-lowering therapies has been developed in recent years, management of lipid-driven CVD risk in the Netherlands remains suboptimal. To lower LDL‑C levels, statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibiting antibodies are the current standard of therapy. With the approval of bempedoic acid and the silencing RNA inclisiran, therapeutic options are expanding continuously. Although the use of triglyceride-lowering therapies remains a matter of debate, post hoc analyses consistently show a benefit in subsets of patients with high triglyceride or low high-density lipoprotein cholesterol levels. Pemafibrate and novel apoC-III could be efficacious options when approved for clinical use. Lp(a)-lowering therapies such as pelacarsen are under clinical investigation, offering a potent Lp(a)-lowering effect. If proven effective in reducing cardiovascular endpoints, Lp(a) lowering holds promise to be the third axis of effective lipid-lowering therapies. Using these three components of lipid-lowering treatment, the contribution of apoB-containing lipid particles to the CVD risk may be fully eradicated in the next decade.


2021 ◽  
Vol 12 (3) ◽  
pp. 517-521
Author(s):  
Jorge Andrés Ojeda Villota ◽  
Javier Alfredo Pérez Martínez ◽  
Luis Alberto Burgos de Moya ◽  
Rodrigo Alfonso Chavez Vega ◽  
Roxana Rivera Valencia ◽  
...  

Hypercholesterolemia (CH) is defined as the elevation of serum cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, which is considered to be one of the most relevant risk factors for triggering cardiovascular disease, for This is vitally important to start treatment, there are several highly useful pharmacological groups for lipid-lowering therapy, among them we highlight the PCSK9 inhibitors, among the molecules that are part of this group we find inclisirán, this being a structure that promises a lot in regarding the management of hypercholesterolemia.


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