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The association of LDLR and PCSK9 variants with LDL-c levels in a black South African population in epidemiological transition / Tertia van ZylVan Zyl, Tertia January 2013 (has links)
Background
Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) are a major risk factor for the development of coronary artery disease (CAD) because of their role in the progression of atherosclerosis. The black South African population is known to have had historically low LDL-c and in the past there was almost no CAD in the population. However, as this population moves through the nutrition transition, LDL-c levels are increasing. LDL-c levels are regulated by the LDL receptors, which is the major protein involved with transporting cholesterol across cell membranes in humans. Proprotein convertase subtilisinlike/kexin type 9 (PCSK9) is another protein involved with the regulation of LDL-c through its role in assisting with the degradation of the LDL receptor. Variants in both genes can cause elevated or lowered LDL-c levels. Very little information is available on the frequency or presence of variants in the low-density lipoprotein receptor (LDLR) and PCSK9 gene in the black South African population and on how these variants associate with LDL-c. The main aim of the study was thus to determine novel and existing genetic variants in these two genes and to describe the manner in which they associate with plasma LDL-c levels in a black South African population undergoing an epidemiological transition.
Methods
The 2005 baseline data from the Prospective Urban and Rural (PURE) study population were used in this study. The study population consisted of apparently healthy black volunteers form the North West province of South Africa, aged 35 to 60 years. Thirty individuals were randomly chosen from the 1860 volunteers to determine the presence of known and novel variants in these genes by automated bidirectional sequencing. The promoter region, exons and flanking regions were sequenced and variants were identified utilising CLC DNA Workbench. Deoxyribonucleic acid (DNA) samples for 1500 individuals of the PURE study population were genotyped by means of a Golden Gate Genotyping Assay. Analyses of covariance (ANCOVA) were used to test for associations between the different genotypes in both the LDLR and PCSK9 genes and LDL-c levels. Haplotypes were generated by using the confidence intervals on the software programme, HaploView. A genetic risk score (GRS) was determined by including variants which associated significantly with LDL-c. The GRS, the haplotypes and the variants that associated significantly with LDL-c were used in separate linear regression models with variants which correlated with LDL-c to determine how all these variables contribute to the differences in LDL-c levels.
Results and discussion
Novel and known variants were identified in both the genes and in total 52 variants were genotyped. Rare variants such as rs17249141 and rs28362286 were detected in the study population and are associated with low levels of LDL-c. The variants identified in the LDLR gene were situated largely in regulatory regions such as the promoter, intron and 3‟untranslated regions. Haplotypes in the LDLR gene with the highest frequency associated with lower LDL-c levels, which could contribute to the study population‟s low mean LDL-c level. Haplotypes identified in the PCSK9 gene had a weaker association with LDL-c levels. The minor allele frequencies of many of the variants differed from those of the European population and therefore the importance of population-specific research cannot be sufficiently emphasised. The GRS, haplotypes and variants used in the regression models to determine whether they contributed to predicting the variance in LDL-c in the study population made a small contribution to explaining this. BMI best explained the variance in LDL-c levels. Older women with a body mass index (BMI)>25kg/m2 were identified as being at greater risk of developing elevated LDL-c levels than the rest of the study population. Heterozygote carriers of variant, rs28362286, had 0.787 mmol/L lower LDL-c than carriers of the wild type and this is associated with a reduced risk of developing CAD.
Conclusion and recommendation
When considering the results mentioned above, adding genetic analysis to explaining the variance in LDL-c levels seems to have its limitations, but the study included only two of many genes that play a role in the metabolism and regulation of LDL-c levels. Incorporating more genes and more variants into analyses and prediction models will add greater value to defining LDL-c levels. Rarer variants with a large impact on protein function, such as rs28362286, have a greater effect on LDL-c levels and could predict the variance better than the common variants. Risk factors such as BMI can also still be trusted to indicate which individuals or groups are at risk of developing elevated LDL-c levels. Health advice should be given to appropriate target groups such as older women with a BMI >25kg/m2 in order to prevent CAD from becoming a burden in this population. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2014
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The association of LDLR and PCSK9 variants with LDL-c levels in a black South African population in epidemiological transition / Tertia van ZylVan Zyl, Tertia January 2013 (has links)
Background
Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) are a major risk factor for the development of coronary artery disease (CAD) because of their role in the progression of atherosclerosis. The black South African population is known to have had historically low LDL-c and in the past there was almost no CAD in the population. However, as this population moves through the nutrition transition, LDL-c levels are increasing. LDL-c levels are regulated by the LDL receptors, which is the major protein involved with transporting cholesterol across cell membranes in humans. Proprotein convertase subtilisinlike/kexin type 9 (PCSK9) is another protein involved with the regulation of LDL-c through its role in assisting with the degradation of the LDL receptor. Variants in both genes can cause elevated or lowered LDL-c levels. Very little information is available on the frequency or presence of variants in the low-density lipoprotein receptor (LDLR) and PCSK9 gene in the black South African population and on how these variants associate with LDL-c. The main aim of the study was thus to determine novel and existing genetic variants in these two genes and to describe the manner in which they associate with plasma LDL-c levels in a black South African population undergoing an epidemiological transition.
Methods
The 2005 baseline data from the Prospective Urban and Rural (PURE) study population were used in this study. The study population consisted of apparently healthy black volunteers form the North West province of South Africa, aged 35 to 60 years. Thirty individuals were randomly chosen from the 1860 volunteers to determine the presence of known and novel variants in these genes by automated bidirectional sequencing. The promoter region, exons and flanking regions were sequenced and variants were identified utilising CLC DNA Workbench. Deoxyribonucleic acid (DNA) samples for 1500 individuals of the PURE study population were genotyped by means of a Golden Gate Genotyping Assay. Analyses of covariance (ANCOVA) were used to test for associations between the different genotypes in both the LDLR and PCSK9 genes and LDL-c levels. Haplotypes were generated by using the confidence intervals on the software programme, HaploView. A genetic risk score (GRS) was determined by including variants which associated significantly with LDL-c. The GRS, the haplotypes and the variants that associated significantly with LDL-c were used in separate linear regression models with variants which correlated with LDL-c to determine how all these variables contribute to the differences in LDL-c levels.
Results and discussion
Novel and known variants were identified in both the genes and in total 52 variants were genotyped. Rare variants such as rs17249141 and rs28362286 were detected in the study population and are associated with low levels of LDL-c. The variants identified in the LDLR gene were situated largely in regulatory regions such as the promoter, intron and 3‟untranslated regions. Haplotypes in the LDLR gene with the highest frequency associated with lower LDL-c levels, which could contribute to the study population‟s low mean LDL-c level. Haplotypes identified in the PCSK9 gene had a weaker association with LDL-c levels. The minor allele frequencies of many of the variants differed from those of the European population and therefore the importance of population-specific research cannot be sufficiently emphasised. The GRS, haplotypes and variants used in the regression models to determine whether they contributed to predicting the variance in LDL-c in the study population made a small contribution to explaining this. BMI best explained the variance in LDL-c levels. Older women with a body mass index (BMI)>25kg/m2 were identified as being at greater risk of developing elevated LDL-c levels than the rest of the study population. Heterozygote carriers of variant, rs28362286, had 0.787 mmol/L lower LDL-c than carriers of the wild type and this is associated with a reduced risk of developing CAD.
Conclusion and recommendation
When considering the results mentioned above, adding genetic analysis to explaining the variance in LDL-c levels seems to have its limitations, but the study included only two of many genes that play a role in the metabolism and regulation of LDL-c levels. Incorporating more genes and more variants into analyses and prediction models will add greater value to defining LDL-c levels. Rarer variants with a large impact on protein function, such as rs28362286, have a greater effect on LDL-c levels and could predict the variance better than the common variants. Risk factors such as BMI can also still be trusted to indicate which individuals or groups are at risk of developing elevated LDL-c levels. Health advice should be given to appropriate target groups such as older women with a BMI >25kg/m2 in order to prevent CAD from becoming a burden in this population. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2014
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What are the effects of lowering LDL-cholesterol on risk of stroke in chronic kidney disease? : evidence from the Study of Heart and Renal Protection (SHARP)Herrington, William Guy January 2013 (has links)
No description available.
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Meta-analysis and systematic review of the benefits expected when the glycaemic index is used in planning diets / Anna Margaretha OppermanOpperman, Anna Margaretha January 2004 (has links)
Motivation: The prevalence of non-communicable diseases such as diabetes mellitus (DM)
and cardiovascular disease (CVD) is rapidly increasing in industrialized societies. Experts
believe that lifestyle, and in particular its nutritional aspects, plays a decisive role in
increasing the burden of these chronic conditions. Dietary habits would, therefore, be
modified to exert a positive impact on the prevention and treatment of chronic diseases of
lifestyle. It is believed that the state of hyperglycaemia that is observed following food intake
under certain dietary regimes contributes to the development of various metabolic conditions.
This is not only true for individuals with poor glycaemic control such as some diabetics, but
could also be true for healthy individuals. It would, therefore, be helpful to be able to reduce
the amplitude and duration of postprandial hyperglycaemia. Selecting the correct type of
carbohydrate (CHO) foods may produce less postprandial hyperglycaemia, representing a
possible strategy in the prevention and treatment of chronic metabolic diseases. At the same
time, a key focus of sport nutrition is the optimal amount of CHO that an athlete should
consume and the optimal timing of consumption. The most important nutritional goals of the
athlete are to prepare body CHO stores pre-exercise, provide energy during prolonged
exercise and restore glycogen stores during the recovery period. The ultimate aim of these
strategies is to maintain CHO availability to the muscle and central nervous system during
prolonged moderate to high intensity exercise, since these are important factors in exercise
capacity and performance. However, the type of CHO has been studied less often and with
less attention to practical concerns than the amount of CHO.
The glycaemic index (GI) refers to the blood glucose raising potential of CHO foods and,
therefore, influences secretion of insulin. In several metabolic disorders, secretion of insulin
is inadequate or impossible, leading to poor glycaemic control. It has been suggested that
low GI diets could potentially contribute to a significant improvement of the conditions
associated with poor glycaemic control. Insulin secretion is also important to athletes since
the rate of glycogen synthesis depends on insulin due to it stimulatory effect on the activity of
glycogen synthase.
Objectives: Three main objectives were identified for this study. The first was to conduct a
meta-analysis of the effects of the GI on markers for CHO and lipid metabolism with the
emphasis on randomised controlled trials (RCT's). Secondly, a systematic review was
performed to determine the strength of the body of scientific evidence from epidemiological
studies combined with RCT's to encourage dieticians to incorporate the GI concept in meal
planning. Finally, a systematic review of the effect of the GI in sport performance was
conducted on all available literature up to date to investigate whether the application of the
GI in an athlete's diet can enhance physical performance.
Methodology: For the meta-analysis, the search was for randomised controlled trials with a
cross-over or parallel design published in English between 1981 and 2003, investigating the
effect of low GI vs high GI diets on markers of carbohydrate and lipid metabolism. The main
outcomes were serum fructosamine, glycosylated haemoglobin (HbA1c), high-density
lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol
(TC) and triacylglycerols (TG). For the systematic review, epidemiological studies as well as
RCT's investigating the effect of LGI vs HGI diets on markers for carbohydrate and lipid
metabolism were used. For the systematic review on the effect of the GI on sport
performance, RCT's with either a cross-over or parallel design that were published in English
between January 1981 and September 2004 were used. All relevant manuscripts for the
systematic reviews as well as meta-analysis were obtained through a literature search on
relevant databases such as the Cochrane Central Register of Controlled Trials, MEDLINE
(1981 to present), EMBASE, LILACS, SPORTDiscus, ScienceDirect and PubMed. This
thesis is presented in the article format.
Results and conclusions of the individual manuscripts:
For the meta-analysis, literature searches identified 16 studies that met the strict
inclusion criteria. Low GI diets significantly reduced fructosamine (p<0.05), HbA1c,
(p<0.03), TC(p<0.0001) and tended to reduce LDL-c (p=0.06) compared to high GI diets.
No changes were observed in HDL-c and TG concentrations. Results from this meta analysis,
therefore, support the use of the GI concept in choosing CHO-containing foods
to reduce TC and improve blood glucose control in diabetics.
The systematic review combined the results of the preceding meta-analysis and results
from epidemiological studies. Prospective epidemiological studies showed improvements
in HDL-c concentrations over longer time periods with low GI diets vs. high GI diets, while
the RCT's failed to show an improvement in HDL-c over the short-term. This could be
attributed to the short intervention period during which the RCT's were conducted.
Furthermore, epidemiological studies failed to show positive relationships between LDL-c
and TC and low GI diets, while RCT's reported positive results on both these lipids with
low GI diets. However, the epidemiological studies, as well as the RCT's showed positive
results with low GI diets on markers of CHO metabolism. Taken together, convincing
evidence from RCT's as well as epidemiological studies exists to recommend the use of
low GI diets to improve markers of CHO as well as of lipid metabolism.
3 From the systematic review regarding the GI and sport performance it does not seem that
low GI pre-exercise meals provide any advantages over high GI pre-exercise meals.
Although low GI pre-exercise meals may better maintain CHO availability during exercise,
low GI pre-exercise meals offer no added advantage over high GI meals regarding
performance. Furthermore, the exaggerated metabolic responses from high GI compared
to low GI CHO seems not be detrimental to exercise performance. However, athletes
who experience hypoglycaemia when consuming CHO-rich feedings in the hour prior to
exercise are advised to rather consume low GI pre-exercise meals. No studies have
been reported on the GI during exercise. Current evidence suggests a combination of
CHO with differing Gl's such as glucose (high GI), sucrose (moderate GI) and fructose
(low GI) will deliver the best results in terms of exogenous CHO oxidation due to different
transport mechanisms. Although no studies are conducted on the effect of the GI on
short-term recovery it is speculated that high GI CHO is most effective when the recovery
period is between 0-8 hours, however, evidence suggests that when the recovery period
is longer (20-24 hours), the total amount of CHO is more important than the type of CHO.
Conclusion: There is an important body of evidence in support of a therapeutic and
preventative potential of low GI diets to improve markers for CHO and lipid metabolism. By
substituting high GI CHO-rich with low GI CHO-rich foods improved overall metabolic control.
In addition, these diets reduced TC, tended to improve LDL-c and might have a positive
effect over the long term on HDL-c. This confirms the place for low GI diets in disease
prevention and management, particularly in populations characterised by already high
incidences of insulin resistance, glucose intolerance and abnormal lipid levels. For athletes it
seems that low GI pre-exercise meals do not provide any advantage regarding performance
over high GI pre-exercise meals. However, low GI meals can be recommended to athletes
who are prone to develop hypoglycaemia after a CHO-rich meal in the hour prior to exercise.
No studies have been reported on the effect of the GI during exercise. However, it has been
speculated that a combination of CHO with varying Gl's deliver the best results in terms of
exogenous CHO oxidation. No studies exist investigating the effect of the GI on short-term
recovery, however, it is speculated that high GI CHO-rich foods are suitable when the
recovery period is short (0-8 h), while the total amount rather than the type of CHO is
important when the recovery period is longer (20-24 h). Therefore, the GI is a scientifically
based tool to enable the selection of CHO-containing foods to improve markers for CHO and
lipid metabolism as well as to help athletes to prepare optimally for competitions.
Recommendations: Although a step nearer has been taken to confirm a place for the GI in
human health, additional randomised, controlled, medium and long-term studies as well as
more epidemiological studies are needed to investigate further the effect of low GI diets on
LDL-c. HDL-c and TG. These studies are essential to investigate the effect of low GI diets
on endpoints such as CVD and DM. This will also show whether low GI diets can reduce the
risk of diabetic complications such as neuropathy and nephropathy. Furthermore, the public
at large must be educated about the usefulness and application of the GI in meal planning.
For sport nutrition, randomised controlled trials should be performed to investigate the role of
the GI during exercise as well as in sports of longer duration such as cricket and tennis.
More studies are needed to elucidate the short-term effect of the GI post-exercise as well as
to determine the mechanism of lower glycogen storage with LGI meals post-exercise. / Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2005.
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Meta-analysis and systematic review of the benefits expected when the glycaemic index is used in planning diets / Anna Margaretha OppermanOpperman, Anna Margaretha January 2004 (has links)
Motivation: The prevalence of non-communicable diseases such as diabetes mellitus (DM)
and cardiovascular disease (CVD) is rapidly increasing in industrialized societies. Experts
believe that lifestyle, and in particular its nutritional aspects, plays a decisive role in
increasing the burden of these chronic conditions. Dietary habits would, therefore, be
modified to exert a positive impact on the prevention and treatment of chronic diseases of
lifestyle. It is believed that the state of hyperglycaemia that is observed following food intake
under certain dietary regimes contributes to the development of various metabolic conditions.
This is not only true for individuals with poor glycaemic control such as some diabetics, but
could also be true for healthy individuals. It would, therefore, be helpful to be able to reduce
the amplitude and duration of postprandial hyperglycaemia. Selecting the correct type of
carbohydrate (CHO) foods may produce less postprandial hyperglycaemia, representing a
possible strategy in the prevention and treatment of chronic metabolic diseases. At the same
time, a key focus of sport nutrition is the optimal amount of CHO that an athlete should
consume and the optimal timing of consumption. The most important nutritional goals of the
athlete are to prepare body CHO stores pre-exercise, provide energy during prolonged
exercise and restore glycogen stores during the recovery period. The ultimate aim of these
strategies is to maintain CHO availability to the muscle and central nervous system during
prolonged moderate to high intensity exercise, since these are important factors in exercise
capacity and performance. However, the type of CHO has been studied less often and with
less attention to practical concerns than the amount of CHO.
The glycaemic index (GI) refers to the blood glucose raising potential of CHO foods and,
therefore, influences secretion of insulin. In several metabolic disorders, secretion of insulin
is inadequate or impossible, leading to poor glycaemic control. It has been suggested that
low GI diets could potentially contribute to a significant improvement of the conditions
associated with poor glycaemic control. Insulin secretion is also important to athletes since
the rate of glycogen synthesis depends on insulin due to it stimulatory effect on the activity of
glycogen synthase.
Objectives: Three main objectives were identified for this study. The first was to conduct a
meta-analysis of the effects of the GI on markers for CHO and lipid metabolism with the
emphasis on randomised controlled trials (RCT's). Secondly, a systematic review was
performed to determine the strength of the body of scientific evidence from epidemiological
studies combined with RCT's to encourage dieticians to incorporate the GI concept in meal
planning. Finally, a systematic review of the effect of the GI in sport performance was
conducted on all available literature up to date to investigate whether the application of the
GI in an athlete's diet can enhance physical performance.
Methodology: For the meta-analysis, the search was for randomised controlled trials with a
cross-over or parallel design published in English between 1981 and 2003, investigating the
effect of low GI vs high GI diets on markers of carbohydrate and lipid metabolism. The main
outcomes were serum fructosamine, glycosylated haemoglobin (HbA1c), high-density
lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol
(TC) and triacylglycerols (TG). For the systematic review, epidemiological studies as well as
RCT's investigating the effect of LGI vs HGI diets on markers for carbohydrate and lipid
metabolism were used. For the systematic review on the effect of the GI on sport
performance, RCT's with either a cross-over or parallel design that were published in English
between January 1981 and September 2004 were used. All relevant manuscripts for the
systematic reviews as well as meta-analysis were obtained through a literature search on
relevant databases such as the Cochrane Central Register of Controlled Trials, MEDLINE
(1981 to present), EMBASE, LILACS, SPORTDiscus, ScienceDirect and PubMed. This
thesis is presented in the article format.
Results and conclusions of the individual manuscripts:
For the meta-analysis, literature searches identified 16 studies that met the strict
inclusion criteria. Low GI diets significantly reduced fructosamine (p<0.05), HbA1c,
(p<0.03), TC(p<0.0001) and tended to reduce LDL-c (p=0.06) compared to high GI diets.
No changes were observed in HDL-c and TG concentrations. Results from this meta analysis,
therefore, support the use of the GI concept in choosing CHO-containing foods
to reduce TC and improve blood glucose control in diabetics.
The systematic review combined the results of the preceding meta-analysis and results
from epidemiological studies. Prospective epidemiological studies showed improvements
in HDL-c concentrations over longer time periods with low GI diets vs. high GI diets, while
the RCT's failed to show an improvement in HDL-c over the short-term. This could be
attributed to the short intervention period during which the RCT's were conducted.
Furthermore, epidemiological studies failed to show positive relationships between LDL-c
and TC and low GI diets, while RCT's reported positive results on both these lipids with
low GI diets. However, the epidemiological studies, as well as the RCT's showed positive
results with low GI diets on markers of CHO metabolism. Taken together, convincing
evidence from RCT's as well as epidemiological studies exists to recommend the use of
low GI diets to improve markers of CHO as well as of lipid metabolism.
3 From the systematic review regarding the GI and sport performance it does not seem that
low GI pre-exercise meals provide any advantages over high GI pre-exercise meals.
Although low GI pre-exercise meals may better maintain CHO availability during exercise,
low GI pre-exercise meals offer no added advantage over high GI meals regarding
performance. Furthermore, the exaggerated metabolic responses from high GI compared
to low GI CHO seems not be detrimental to exercise performance. However, athletes
who experience hypoglycaemia when consuming CHO-rich feedings in the hour prior to
exercise are advised to rather consume low GI pre-exercise meals. No studies have
been reported on the GI during exercise. Current evidence suggests a combination of
CHO with differing Gl's such as glucose (high GI), sucrose (moderate GI) and fructose
(low GI) will deliver the best results in terms of exogenous CHO oxidation due to different
transport mechanisms. Although no studies are conducted on the effect of the GI on
short-term recovery it is speculated that high GI CHO is most effective when the recovery
period is between 0-8 hours, however, evidence suggests that when the recovery period
is longer (20-24 hours), the total amount of CHO is more important than the type of CHO.
Conclusion: There is an important body of evidence in support of a therapeutic and
preventative potential of low GI diets to improve markers for CHO and lipid metabolism. By
substituting high GI CHO-rich with low GI CHO-rich foods improved overall metabolic control.
In addition, these diets reduced TC, tended to improve LDL-c and might have a positive
effect over the long term on HDL-c. This confirms the place for low GI diets in disease
prevention and management, particularly in populations characterised by already high
incidences of insulin resistance, glucose intolerance and abnormal lipid levels. For athletes it
seems that low GI pre-exercise meals do not provide any advantage regarding performance
over high GI pre-exercise meals. However, low GI meals can be recommended to athletes
who are prone to develop hypoglycaemia after a CHO-rich meal in the hour prior to exercise.
No studies have been reported on the effect of the GI during exercise. However, it has been
speculated that a combination of CHO with varying Gl's deliver the best results in terms of
exogenous CHO oxidation. No studies exist investigating the effect of the GI on short-term
recovery, however, it is speculated that high GI CHO-rich foods are suitable when the
recovery period is short (0-8 h), while the total amount rather than the type of CHO is
important when the recovery period is longer (20-24 h). Therefore, the GI is a scientifically
based tool to enable the selection of CHO-containing foods to improve markers for CHO and
lipid metabolism as well as to help athletes to prepare optimally for competitions.
Recommendations: Although a step nearer has been taken to confirm a place for the GI in
human health, additional randomised, controlled, medium and long-term studies as well as
more epidemiological studies are needed to investigate further the effect of low GI diets on
LDL-c. HDL-c and TG. These studies are essential to investigate the effect of low GI diets
on endpoints such as CVD and DM. This will also show whether low GI diets can reduce the
risk of diabetic complications such as neuropathy and nephropathy. Furthermore, the public
at large must be educated about the usefulness and application of the GI in meal planning.
For sport nutrition, randomised controlled trials should be performed to investigate the role of
the GI during exercise as well as in sports of longer duration such as cricket and tennis.
More studies are needed to elucidate the short-term effect of the GI post-exercise as well as
to determine the mechanism of lower glycogen storage with LGI meals post-exercise. / Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2005.
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The development of lipoprotein apheresis in Saxony in the last yearsKuss, Solveig Frieda Rosa, Schatz, Ulrike, Tselmin, Sergey, Fischer, Sabine, Julius, Ulrich 19 March 2024 (has links)
Methods
Three hundred thirty-nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013.
Results
Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high-risk group. For some cardiovascular regions even no events could be observed.
Conclusions
The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018.
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Role of PFOA and PFOS on Serum Apolipoprotein B, NHANES, 2005-2006Maisonet, Mildred, Yadav, Ruby, Leinaar, Edward 01 September 2015 (has links)
Background: Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been associated with higher circulating concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). ApoB is the primary apolipoprotein component of LDL-C, and acts as a ligand for LDL-C receptors in various cells throughout the body. Circulating concentrations of ApoB are considered to be a better indicator of heart disease risk than TC or LDL-C. Objectives: Explore associations of concentrations of PFOA and PFOS with serum ApoB in adults. Methods: We analyzed data from 2744, 20-80 years old participants in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Linear regression models were used to estimate adjusted predicted means of serum ApoB (in g/L) for quartiles of PFOA and PFOS (in ng/mL) to describe patterns of associations. Results: Adjusted predicted mean concentrations of serum ApoB did not appear to vary meaningfully with increasing concentrations of PFOA (Q1 1.11, Q2 1.02, Q3 1.01, Q4 1.02) or increasing concentrations of PFOS (Q1 1.06, Q2 1.05, Q3 1.07, Q4 0.99) in study participants. Conclusions: Exposure to PFOA or PFOS does not appear to alter Apo B concentrations in adults.
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Development of Inhibitors of Human PCSK9 as Potential Regulators of LDL-Receptor and CholesterolAlghamdi, Rasha Hassen January 2014 (has links)
Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) is the ninth member of the Ca+2-dependent mammalian proprotein convertase super family of serine endoproteases that is structurally related to the bacterial subtilisin and yeast kexin enzymes. It plays a critical role in the regulation of lipid metabolism and cholesterol homeostasis by binding to and degrading low-density lipoprotein-receptor (LDL-R) which is responsible for the clearance of circulatory LDL-cholesterol from the blood. Owing to this functional property, there is plenty of research interest in the development of functional inhibitors of PCSK9 which may find important biochemical applications as therapeutic agents for lowering plasma LDL-cholesterol. The catalytic domain of PCSK9 binds to the EGF-A domain of LDL-R on the cell surface to form a stable complex and re-routes the receptor from its normal endosomal recycling pathway to the lysosomal compartments leading to its degradation. Owing to these findings, we propose that selected peptides from PCSK9 catalytic domain, particularly its disulphide (S-S) bridged loop1 323-358 and loop2 365-385, are likely to exhibit strong affinity towards the EGF-A domain of LDL-R. Several regular peptides along with corresponding all- dextro and retro-inverse peptides as well as the gain-of-function mutant variants were designed and tested for their regulatory effects towards LDL-R expression and PCSK9-binding in human hepatic HepG2 and mouse hepatic Hepa1c1c7 cells. Our data indicated that disulfide bridged loop1-hPCSK9323-358 and its H357 mutant as well as two short loop2-hPCSK9372-380 and its Y374 mutant peptides modestly promote the LDL-R protein levels. Our study concludes that specific peptides from the PCSK9 catalytic domain can regulate LDL-R and may be useful for development of novel class of therapeutic agents for cholesterol regulation.
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BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
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BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
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