Evidence of age-dependent genetic influences on plasma total cholesterol

Author(s):  
Rita Middelberg ◽  
Andrew C. Heath ◽  
Nicholas G. Martin ◽  
John B. Whitfield

Background Causes of variation in cardiovascular risk factors include biological variation within individuals, and more permanent differences between individuals, which are at least partly genetic in origin. We have compared the magnitude of genetic and non-genetic factors within and across occasions through repeated measures of plasma cholesterol in twin subjects, and have also determined how far the same genes affect cholesterol levels at different ages. Methods Data on plasma total cholesterol were extracted for 208 twin pairs who had provided blood on up to six occasions across a period of 17 years. They were aged 18–30 years at the time of first study and 30–47 at the time of the last. Multivariate models of variation due to genetic, shared environmental and unique environmental factors were fitted to the multi-occasion data and the proportions of variation due to these factors were estimated. Results One genetic factor influenced plasma cholesterol on all occasions and a second genetic factor only influenced cholesterol results on the fifth and sixth occasions 10–17 years after the first. Environmental factors did not have significant long-term effects. Conclusions We conclude that individuals’ long-term mean plasma cholesterol values are strongly genetically determined, but that some of these genes are age-specific in their effects.

1961 ◽  
Vol 7 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Gordon Fels ◽  
Eugene Kanabrocki ◽  
Ervin Kaplan

Abstract The experimental production of hypercholesteremia in rabbits by three independent methods—namely, high-fat feeding, cortisone injection, and Tween-80 injection—results in an elevated plasma total cholesterol, whereas the total RBC cholesterol remains constant. Previous work on plasma and red cell cholesterol in humans has been substantiated. Normal total plasma and red cell cholesterol values are 187 ± 32 and 129 ± 20 mg.%, respectively. Elevated plasma total cholesterol occurring in coronary arteriosclerosis, diabetes, nephritis, hypothyroid, Hodgkin's disease, and obesity does not affect the erythrocyte levels. Elevated erythrocyte total cholesterol levels occur in sickle cell and pernicious anemia accompanied by slightly sub-normal plasma levels. A hypothesis is advanced to explain the variability of plasma cholesterol and the relative constancy of red cell cholesterol.


1979 ◽  
Vol 57 (s5) ◽  
pp. 405s-407s ◽  
Author(s):  
A. Lehtonen ◽  
J. Viikari

1. We studied the effect on plasma lipids of sotalol given orally over a 12 month period to patients with essential hypertension. 2. Plasma free fatty acid concentration was lower than initially at 1, 3, 6 and 12 months. The difference was significant (P < 0·01) at 1 and 3 months. 3. Plasma cholesterol (VLDL + LDL-cholesterol) increased during treatment. Plasma total cholesterol increased from 5·49 ± sd 0·94 mmol/l at the beginning to 6·37 ± 1·10 mmol/l at 12 months (P < 0·01). 4. HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol decreased significantly. The ratios were 0·28 and 0·18 at the beginning and at 12 months respectively (P < 0·001). 5. Plasma triglycerides increased simultaneously from 1·14 ± 0·31 to 1·89 ± 0·99 mmol/l (P < 0·01).


2005 ◽  
Vol 230 (7) ◽  
pp. 472-478 ◽  
Author(s):  
Sun-Ok Lee ◽  
Andrean L. Simons ◽  
Patricia A. Murphy ◽  
Suzanne Hendrich

A study was conducted in hamsters to determine if group B soyasaponins improve plasma cholesterol status by increasing the excretion of fecal bile acids and neutral sterols, to identify group B soyasaponin metabolites, and to investigate the relationship between a fecal group B soyasaponin metabolite and plasma lipids. Twenty female golden Syrian hamsters, 11–12 weeks old and 85–125 g, were randomly assigned to a control diet or a similar diet containing group B soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed group B soyasaponins had significantly lower plasma total cholesterol (by 20%), non–high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by 18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to HDL cholesterol was significantly lower (by 13%) in hamsters fed group B soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile acids and neutral sterols was significantly greater (by 105% and 85%, respectively) in soyasaponin-fed hamsters compared with those fed casein (P < 0.05). Compared with casein, group B soyasaponins lowered plasma total cholesterol levels and non-HDL cholesterol levels by a mechanism involving greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B soyasaponins statistically clustered into two fecal soyasaponin metabolite–excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high and low producers of this soyasaponin metabolite were compared for plasma cholesterol status, the high producers showed a significantly lower total-cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 ± 0.7 vs. 1.59 ± 0.13; P < 0.03). Greater production of group B soyasaponin metabolite in hamsters was associated with better plasma cholesterol status, suggesting that gut microbial variation in soyasaponin metabolism may influence the health effects of group B soyasaponins.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
H Bergum ◽  
I Sandven ◽  
TO Klemsdal

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Norwegian health department Background The evidence of the long-term effects of multiple lifestyle intervention on cardiovascular risk is uncertain. We aimed to summarize the evidence from randomized clinical trials examining the efficacy of lifestyle intervention on major cardiovascular risk factors in subjects at high cardiovascular risk. Methods  Eligible trials investigated the impact of lifestyle intervention versus usual care with minimum 24 months follow-up, reporting more than one major cardiovascular risk factor. A literature search updated April 15, 2020 identified 12 eligible studies. The results from individual trials were combined using fixed and random effect models, using the standardized mean difference (SMD) to estimate effect sizes. Small-study effect was evaluated, and heterogeneity between studies examined by subgroup and meta-regression analyses considering patient- and study-level variables. Results  Small-study effect was not identified. Lifestyle intervention reduced systolic blood pressure modestly with an estimated SMD of -0.13, 95% confidence interval (CI): -0.21 to -0.04, with moderate heterogeneity (I² = 59%), corresponding to a mean difference of approximately 2 mmHg (MD = -1.86, 95% CI: -3.14 to -0.57, p = 0.0046). This effect disappeared in the subgroup of trials judged at low risk of bias (SMD = 0.02, 95% CI: -0.08 to 0.11). For the outcome total cholesterol SMD was -0.06, 95% CI: -0.13 to 0.00, with no heterogeneity (I² = 0%), indicating no effect of the intervention. Conclusion  Lifestyle intervention resulted in only a modest effect on systolic blood pressure and no effect on total cholesterol after 24 months. Further lifestyle trials should consider the challenge of maintaining larger long-term benefits to ensure impact on cardiovascular outcomes.


2013 ◽  
Vol 28 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Patrice Berque ◽  
Heather Gray ◽  
Angus McFadyen

Focal hand dystonia (FHD) in musicians is a painless, task-specific motor disorder characterized by involuntary loss of control of individual finger movements. The aim of this study was to investigate the long-term effects of a combined behavioral therapy intervention aimed at normalizing finger movement patterns. METHODS: Eight musicians with FHD had taken part in the 1-year study involving intensive constraint-induced therapy and motor control retraining at slow speed as the interventions. Four of these subjects volunteered to take part in this 4-year follow-up. A quasi-experimental, repeated measures design was used, with 9 testing sessions over 4 years. Video recordings of the subjects playing two pieces were used for data analysis. The Frequency of Abnormal Movements scale (FAM) was the main outcome measure. It was hypothesized that there would be significant differences in FAM scores achieved over the 4-year period. RESULTS: The results from the ANOVA revealed a significant decrease, by approximately 80%, in the number of abnormal movements for both pieces over the 4-year period (F=7.85, df=8, p<0.001). Tukey’s post-hoc test revealed that significant improvements occurred after 6 months of therapy (p-values between p<0.001 and p=0.044). Although the results were not significant between month 12 and follow-up at year 4, the trend revealed that the progress achieved during the first year of intensive retraining was maintained at year 4. CONCLUSIONS: A 1-year period of intensive task-specific retraining may be a successful strategy with long-term, lasting effects for the treatment of musician’s FHD. Results suggest that retraining strategies may need to be carried out for at least 6 months before statistically significant changes are noted.


2020 ◽  
Vol 21 (24) ◽  
pp. 9737
Author(s):  
Beata Olas

Recent evidence suggests that probiotics, prebiotics and synbiotics may serve as important dietary components in the prevention (especially) and treatment of cardiovascular diseases (CVD), but the recommendations for their use are often based on brief reports and small clinical studies. This review evaluates the current literature on the correlation between CVD and probiotics, prebiotics and synbiotics. Although research on probiotics, prebiotics and synbiotics has grown exponentially in recent years, particularly regarding the effect of probiotics on CVD, their mechanisms have not been clearly defined. It has been proposed that probiotics lower cholesterol levels, and may protect against CVD, by increasing bile salt synthesis and bile acid deconjugation. Similar effects have also been observed for prebiotics and synbiotics; however, probiotics also appear to have anti-oxidative, anti-platelet and anti-inflammatory properties. Importantly, probiotics not only have demonstrated effects in vitro and in animal models, but also in humans, where supplementation with probiotics decreases the risk factors of CVD. In addition, the properties of commercial probiotics, prebiotics and synbiotics remain undetermined, and further experimental research is needed before these substances can be used in the prevention and treatment of CVD. In particular, well-designed clinical trials are required to determine the influence of probiotics on trimethylamine-N-oxide (TMAO), which is believed to be a marker of CVDs, and to clarify the long-term effects, and action, of probiotic, prebiotic and synbiotic supplementation in combination with drug therapy (for example, aspirin). However, while it cannot be unequivocally stated whether such supplementation yields benefits in the prevention and treatment of CVDs, it is important to note that clinical studies performed to date have not identified any side-effects to use.


1962 ◽  
Vol 8 (2) ◽  
pp. 105-112 ◽  
Author(s):  
G S Duboff ◽  
W W Stevenson

Abstract A procedure is outlined for the ultramicro determination of total cholesterol that gives results in excellent agreement with classic methods. The determination requires 40 µl. of plasma obtained from a finger-tip puncture and special handling of precipitated proteins. By the use of the described procedure plasma cholesterol levels have been estimated 4 times daily over a period of 8 weeks in young men undergoing rigorous physical training and 3 times daily in women during the menstrual cycle. A striking fall in total plasma cholesterol was observed in men following physical conditioning in contrast to controls, and a similar decrease was observed in women with normal menstrual cycles in contrast to women with an anovulatory menses. It is suggested that the total cholesterol decrease in the female coincides with the phase in the menstrual cycle when estrogen activity is maximal and that the lowering of total cholesterol in men, following physical conditioning, may be due to an increased production of endogenous androgens with a consequent increase in conversion of these steroids to estrogens.


Hypertension ◽  
2015 ◽  
Vol 65 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Michihiro Satoh ◽  
Takayoshi Ohkubo ◽  
Kei Asayama ◽  
Yoshitaka Murakami ◽  
Masaru Sakurai ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1272 ◽  
Author(s):  
Jung Kim ◽  
Wayne Campbell

Whole egg is a food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. We assessed the effect of co-consuming cooked whole egg (CWE) on dietary cholesterol absorption from two randomized-crossover studies. For study 1, 16 men consumed raw vegetables with no egg, 75 g CWE, or 150 g CWE. For study 2, 17 women consumed cooked vegetables with no egg or 100 g CWE. Triacylglycerol-rich lipoprotein fractions (TRL) were isolated from collected blood. In study 1, total-cholesterol areas under the curve (AUC)0–10h in TRL were not different but triacylglycerol AUC0–10h in TRL was greater for 150 g CWE vs. 75 g CWE and no egg. Similarly, in study 2, total-cholesterol AUC0–10h in TRL was not different but triacylglycerol AUC0–10h in TRL was greater for 100 g CWE vs. no egg. In both studies, whole egg consumption did not affect plasma total-cholesterol AUC0–10h, while triacylglycerol AUC0–10h was increased. These results suggest that the dietary cholesterol in whole egg was not well absorbed, which may provide mechanistic insight for why it does not acutely influence plasma total-cholesterol concentration and is not associated with longer-term plasma cholesterol control.


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