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Association of Apolipoprotein E (Apo E) polymorphism with the prevalence of metabolic syndrome (MetS): the National Heart, Lung and Blood Institute Family Heart StudyLai, Lana Yin Hui January 2013 (has links)
BACKGROUND & AIMS - Metabolic syndrome (MetS), characterized by abdominal obesity,
atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major
public health concern in the United States. The effect of Apolipoprotein E (Apo E)
polymorphism has been relatively well studied in relation to cardiovascular disease;
however, its effects on MetS are not well established.
METHODS - We conducted a cross-sectional study consisting of 1,551 participants from
the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the
relation of Apo E polymorphism with the prevalence of MetS. Information on the
different Apo E genotypes was extracted from the database and we defined MetS
according to the AHA-NHLBI-IDF-WHO Harmonized Criteria. We used generalized
estimating equations to estimate adjusted odds ratios for prevalent MetS and the
Bonferroni correction to account for multiple testing in the secondary analysis.
RESULTS – Our study population had a mean age (SD) of 56.5 (11.0) years and 49.7% had
MetS. There was no association between the Apo E genotypes and MetS. The
multivariable adjusted ORs (95% CI) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62-
1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the *e3/e3, *e2/e2,
*e2/e3, *e2/e4, *e3/e4 and *e4/e4 genotype respectively. In a secondary analysis, the
*e2/e3 genotype was associated with lower HDL levels, with the multivariable adjusted
ORs (95% CI) of 0.59 (0.36-0.95) when compared to the reference *e3/e3 genotype.
CONCLUSIONS - Our findings do not support an association between Apo E polymorphism
and MetS in a multi-center population based study of predominantly white US men and
women. The *e2/e3 genotype was associated with lower HDL levels as compared to the
*e3/e3 genotype.
KEY WORDS: Apolipoprotein E (Apo E) polymorphism, metabolic syndrome, blood
pressure, glucose, waist circumference, triglycerides, high-density lipoprotein cholesterol
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Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-inflammatory Pathways / microRNA-33を遺伝的に欠失させると、複数の抗炎症メカニズムを介して炎症と腹部大動脈瘤形成が緩和されるNakao, Tetsushi 23 January 2018 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20801号 / 医博第4301号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 山下 潤, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Relationship Between Lipid Profiles and Hypertension: A Cross-Sectional Study of 62,957 Chinese Adult MalesChen, Siwei, Cheng, Wenke 10 October 2023 (has links)
Background
Patterns of dyslipidemia and incidence of hypertension have been rarely reported in Asian populations with inconsistent findings. To accumulate further evidence in Asian populations, the study aimed to investigate the relationship between lipid profiles and hypertension in Chinese adult males.
Methods
We conducted a cross-sectional study based on the data from the DATADRYAD database. The overall population was divided into hypertensive and non-hypertensive groups based on baseline blood pressure levels. For continuous variables, Mann-Whitney test was performed between two groups, while Kruskal-Wallis and Dunn tests were used among multiple groups. The chi-square test was carried out for dichotomous variables. Spearman's correlation coefficient was employed to assess the association between systolic blood pressure (SBP), diastolic blood pressure (DBP) and lipid profiles, whereas the relationship between lipid profiles and the incidence of hypertension was evaluated using multivariate logistic regression. The Bayesian network (BN) model was adopted to investigate the relationship between clinical characteristics and hypertension, and the importance of related predictor to the incidence of hypertension was obtained to make conditional probability analysis.
Results
Finally, totally 62,957 participants were included in this study. In the lipid profiles, total cholesterol (TC), low-density cholesterol (LDL-c), and non- high-density lipoprotein cholesterol (non-HDL-c) were higher in the hypertensive population (p <0.001). In the fully multivariate model, for every 1 mg/dl increase in TC, LDL-c and non-HDL, the risk of hypertension increased by 0.2% [1.002 (1.001–1.003)], 0.1% [1.001 (1.000–1.002)], and 0.1% [1.001 (1.000–1.002)]. Meanwhile, HDL-c became positively associated with the incidence of hypertension (p for trend < 0.001) after adjusting for the body mass index (BMI), and 1 mg/dl increment in HDL-c increased the risk of hypertension by 0.2% [1.002 (1.000–1.002)] after fully adjusting for multiple variables. Furthermore, the BN showed that the importance of age, BMI, fasting plasma glucose (FPG), and TC to the effect of hypertension is 43.3, 27.2, 11.8, and 5.1%, respectively.
Conclusion
Elevated TC, LDL-c, and non-HDL-c were related to incidence of hypertension in Chinese adult males, whereas triglycerides (TG) was not significantly associated. The relationship between HDL-c and hypertension incidence shifted from no association to a positive correlation after adjusting for the BMI. Moreover, the BN model displayed that age, the BMI, FPG, and TC were strongly associated with hypertension incidence.
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Association of Lipid Levels With the Prevalence of Hypertension in Chinese Women: A Cross-Sectional Study Based on 32 Health Check CentersDeng, Guizhi, Li, Yunjie, Cheng, Wenke 19 October 2023 (has links)
Background: Dyslipidemia is strongly associated with the development of hypertension.
In our previous study, it was shown that elevated TC, LDL-c, and non-HDL-c were
associated with the prevalence of hypertension in Chinese men, whereas the relationship
between HDL-c and hypertension shifted from no association to a positive association
after adjusting for the BMI. To further accumulate epidemiological evidence in Asian
women, this study aimed to investigate the relationship between lipid profile and
prevalence of hypertension in Chinese adult women.
Methods: This is a cross-sectional study including 54,099 Chinese women aged>20
years at 32 health screening centers in 11 cities from 2010-2016. The original data were
obtained from DATADRYAD database (www.datadryad.org). Besides, the overall women
were classified into non-hypertensive and hypertensive groups based on baseline blood
pressure levels. Differences between the two groups were examined by Man-Whitney test
or Chi-square test. Spearman’s correlation coefficient was employed to evaluate the
correlation between systolic blood pressure (SBP), diastolic blood pressure (DBP) and
lipid profiles. Multivariate logistic regression was performed to estimate the relationship
between different lipid levels and the prevalence of hypertension. Odds ratios (ORs) and
95% confidence intervals (CIs) indicated the risk of lipid and hypertension. Bayesian model
(BN) model was constructed to further assess the relationship between baseline
characteristics and the prevalence of hypertension, as well as the importance of each
variable for the prevalence of hypertension.
Results: Compared to the non-hypertensive population, the hypertensive population was
older, and had the higher body mass index (BMI), total cholesterol (TC), low-density
lipoprotein cholesterol (LDL-c), serum creatinine (Scr), fasting blood glucose (FPG), blood
urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST),
and non-high-density lipoprotein cholesterol (non-HDL-c), but HDL-c and the presence
concerning the family history of diabetes were lower. Multivariate logistic regression
analysis revealed that TC, LDL-c, and non-HDL-c showed a positive trend with hypertension risk (p for trend < 0.05) whereas TC and HDL-c were not significantly associated
with hypertension prevalence. Moreover, each 1 mg/dl increase in TC, LDL, and non-HDL
hypertension prevalence increased by 0.2% [1.002 (1.000-1.003)], 0.2% [1.002 (1.000-
1.004)], and 0.2% [1.002(1.001-1.004)], respectively. BN suggested that the importance of
age, BMI, FPG, non-HDL-c on the prevalence of hypertension was 52.73%, 24.98%, 11.22%,
and 2.34%, respectively.
Conclusion: Overall, in Chinese adult women, TC, LDL-c and non-HDL-c levels were higher
and HDL-c level was lower in the hypertensive population, whereas TG did not differ
significantly from the non-hypertensive population. Meanwhile, TC, LDL-c, and non-HDL-c
were positively associated with prevalence of hypertension, and HDL-c was negatively
associated with prevalence of hypertension but became nonsignificant after full adjustment
for variables. Moreover, BN model suggested that age, BMI, FPG, and non-HDL-c had a
greater effect on the development of hypertension.
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Differences in Lipid Profiles and Atherogenic Indices Between Hypertensive and Normotensive Populations: A Cross-Sectional Study of 11 Chinese CitiesCheng, Wenke, Wang, Lili, Chen, Siwei 03 July 2023 (has links)
Background: Several previous studies have reported that dyslipidemia is associated
with the risk of hypertension, but these studies are mainly conducted in European and
US populations, with a very few studies in the Asian population. Moreover, the effects
of atherosclerotic indices, including atherogenic coefficient (AC) and atherogenic risk of
plasma (AIP), on hypertension in Asians have not been well described so far.
Methods: From 2010 to 2016, altogether 211,833 Chinese adults were ultimately
recruited at the health centers in 11 Chinese cities (including Shanghai, Beijing,
Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, and
Nantong). Differences in continuous variables between the two groups were analyzed
by the Mann–Whitney test, while those in categorical variables were examined by the
Chi-squared test. Logistic regression was applied to evaluate the association between
lipid profiles and the risk of hypertension. The predictive values of AC and AIP for the
incidence of hypertension were analyzed using the area under the receiver operating
characteristic (ROC) curve. Meanwhile, Bayesian network (BN) models were performed
to further analyze the associations between the different covariates and the incidence
of hypertension.
Results: A total of 117,056 participants were included in the final analysis. There
were significant differences in baseline characteristics between normotension and
hypertension groups (p < 0.001). In multivariate logistic regression, the risk of
hypertension increased by 0.2% (1.002 [1.001–1.003]), 0.2% (1.002 [1.001–1.003]), and
0.2% (1.002 [1.001–1.003]) per 1 mg/dl increase in total cholesterol (TC), low-density
lipoprotein (LDL), and non-high-density lipoprotein cholesterol (non-HDL-c), respectively.
However, after adjusting for body mass index (BMI), an increase in HDL level was
associated with a higher risk of hypertension (p for a trend < 0.001), and the risk of
hypertension increased by 0.6% per 1 mg/dl increase in HDL-c (1.006 [1.003–1.008]).
In women, AC had the highest predictive value for the incidence of hypertension with
an area under the curve (AUC) of 0.667 [95% confidence interval (CI): 0.659–0.674].
BN models suggested that TC and LDL were more closely related to the incidence
of hypertension.
Conclusions: Overall, lipid profiles were significantly abnormal in the hypertensive
population than in the normotensive population. TC and LDL were strongly associated
with the incidence of hypertension. TC, LDL, and non-HDL-c levels show a positive
association, HDL-c shows a negative association, while TG is not significantly associated
with the risk of hypertension. After adjusting for BMI, HDL-c turns out to be positively
associated with the risk of hypertension. In addition, AC has a good predictive value for
the incidence of hypertension in women.
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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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Alcohol intake and cardiovascular function of black South Africans : a 5-year prospective study / Mandlenkosi Caswell ZatuZatu, Mandlenkosi Caswell January 2015 (has links)
Motivation
Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive
alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse
continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of
urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In
addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular
consequences that include injury, risky sexual behaviour, violent crime and family dysfunction
among black South Africans, contributing to high mortality. Moreover, the highest number of
individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable
to high intake of alcohol. HIV remains a major concern in South Africa with significant funding
diverted to address the pandemic. The continued increases in mortality from preventable
outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation,
poverty and dysfunctional health systems working with limited budgets. These are some of the
factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although
there is enough evidence that links excessive drinking with hypertension and CVD, the markers of
alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate
deficient transferrin – are still not specific enough to isolate other confounding factors in the
association of alcohol intake with CVD. The markers of alcohol that independently predict CVD
and mortality need to be explored. Finally, the severe lack of longitudinal investigations on
alcohol-related hypertension development and total mortality in black South Africans has
compromised the early identification of risk factors associated with these outcomes. This study
will therefore attempt to address the limited availability of longitudinal studies and stimulate
interest for continued investigation.
Aim
The aim of this study was to investigate whether alcohol intake of black South Africans is related
to specific measures of cardiovascular function (change in blood pressure (BP), hypertension
development) and mortality over a period of 5 years.
Methodology
This study was based on the international Prospective Urban and Rural Epidemiology (PURE)
study which includes 26 countries, investigating the cause and development of cardiovascular
risk factors in low, middle and high income countries. This South African leg of the PURE study
started in 2005 in which the baseline data was collected from 2021 black South Africans from
rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven
participants presented with missing data, leaving 2010 participants with complete datasets at
baseline. However, data from these 11 participants was useful, especially for Chapter 4. All
participants gave informed consent and the Ethics committee of the North-West University
(Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010.
General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular
measurements were taken both at baseline and follow-up using appropriate methods. We also
collected blood samples and performed biochemical analyses for lipid markers, liver enzymes,
inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we
obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and
death certificates.
We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and
proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline
and follow-up variables. Furthermore, we employed single and partial linear regression analyses
to correlate alcohol markers with each other and with the cardiovascular measures. Multiple
regression analyses were used to correlate dependent variables in the study with various
independent variables as required. Finally, we employed multivariable-adjusted Cox regression
analyses to assess the association of the selected alcohol markers with mortality while adjusting
for several independent variables.
Results and Conclusions of each manuscript
- With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake
estimates with GGT and %CDT, considering their relationship with percentage change in
brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The
results indicated that only self-reported alcohol intake independently predicted % change in
brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT.
Self-reported alcohol intake seems to be an important measure to implement by health
systems in low income areas of sub-Saharan Africa, where honest reporting is expected.
- Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic
fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the
cardiovascular and metabolic characteristics of excessive alcohol users and individuals with
suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex
and cardiometabolic profiles characterised excessive alcohol users and individuals suspected
with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive
alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up
the higher proportion of this group. In excessive alcohol users systolic blood pressure and
pulse pressure were independently associated with high-density lipoprotein cholesterol.
Diastolic blood pressure showed a significant correlation with waist circumference. These
disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify
individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These
results emphasise the importance of modifiable risk factors as the main contributors to CVD
and that lifestyle change should be the main focus in developing countries such as South
Africa.
- The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported
alcohol intake, GGT and %CDT) that related best with hypertension development,
cardiovascular and all-cause mortality over 5 years in the same population of black South
Africans. We found that GGT was the only independent predictor of hypertension
development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol
intake predicted incident hypertension, confirming our findings from Chapter 4. The third
marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome
variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in
low-resource primary healthcare settings, measurement of GGT is encouraged due to its
predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic
steatohepatitis and obesity - all known to have severe cardiovascular consequences.
Discussion and Conclusions
Excessive alcohol intake remains a major concern in the development of hypertension, CVD and
premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity,
self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers
that independently predicted 5-year change in BP, hypertension development and total mortality
in this population. Serum %CDT did not show any association with the mentioned cardiovascular
markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e.
with high GGT levels who do not consume alcohol) are typically obese women, whereas lean
men were more likely to have high alcohol consumption. Further prospective investigations are
encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting
estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly
specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in
this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015
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18 |
Alcohol intake and cardiovascular function of black South Africans : a 5-year prospective study / Mandlenkosi Caswell ZatuZatu, Mandlenkosi Caswell January 2015 (has links)
Motivation
Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive
alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse
continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of
urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In
addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular
consequences that include injury, risky sexual behaviour, violent crime and family dysfunction
among black South Africans, contributing to high mortality. Moreover, the highest number of
individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable
to high intake of alcohol. HIV remains a major concern in South Africa with significant funding
diverted to address the pandemic. The continued increases in mortality from preventable
outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation,
poverty and dysfunctional health systems working with limited budgets. These are some of the
factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although
there is enough evidence that links excessive drinking with hypertension and CVD, the markers of
alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate
deficient transferrin – are still not specific enough to isolate other confounding factors in the
association of alcohol intake with CVD. The markers of alcohol that independently predict CVD
and mortality need to be explored. Finally, the severe lack of longitudinal investigations on
alcohol-related hypertension development and total mortality in black South Africans has
compromised the early identification of risk factors associated with these outcomes. This study
will therefore attempt to address the limited availability of longitudinal studies and stimulate
interest for continued investigation.
Aim
The aim of this study was to investigate whether alcohol intake of black South Africans is related
to specific measures of cardiovascular function (change in blood pressure (BP), hypertension
development) and mortality over a period of 5 years.
Methodology
This study was based on the international Prospective Urban and Rural Epidemiology (PURE)
study which includes 26 countries, investigating the cause and development of cardiovascular
risk factors in low, middle and high income countries. This South African leg of the PURE study
started in 2005 in which the baseline data was collected from 2021 black South Africans from
rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven
participants presented with missing data, leaving 2010 participants with complete datasets at
baseline. However, data from these 11 participants was useful, especially for Chapter 4. All
participants gave informed consent and the Ethics committee of the North-West University
(Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010.
General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular
measurements were taken both at baseline and follow-up using appropriate methods. We also
collected blood samples and performed biochemical analyses for lipid markers, liver enzymes,
inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we
obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and
death certificates.
We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and
proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline
and follow-up variables. Furthermore, we employed single and partial linear regression analyses
to correlate alcohol markers with each other and with the cardiovascular measures. Multiple
regression analyses were used to correlate dependent variables in the study with various
independent variables as required. Finally, we employed multivariable-adjusted Cox regression
analyses to assess the association of the selected alcohol markers with mortality while adjusting
for several independent variables.
Results and Conclusions of each manuscript
- With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake
estimates with GGT and %CDT, considering their relationship with percentage change in
brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The
results indicated that only self-reported alcohol intake independently predicted % change in
brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT.
Self-reported alcohol intake seems to be an important measure to implement by health
systems in low income areas of sub-Saharan Africa, where honest reporting is expected.
- Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic
fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the
cardiovascular and metabolic characteristics of excessive alcohol users and individuals with
suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex
and cardiometabolic profiles characterised excessive alcohol users and individuals suspected
with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive
alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up
the higher proportion of this group. In excessive alcohol users systolic blood pressure and
pulse pressure were independently associated with high-density lipoprotein cholesterol.
Diastolic blood pressure showed a significant correlation with waist circumference. These
disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify
individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These
results emphasise the importance of modifiable risk factors as the main contributors to CVD
and that lifestyle change should be the main focus in developing countries such as South
Africa.
- The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported
alcohol intake, GGT and %CDT) that related best with hypertension development,
cardiovascular and all-cause mortality over 5 years in the same population of black South
Africans. We found that GGT was the only independent predictor of hypertension
development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol
intake predicted incident hypertension, confirming our findings from Chapter 4. The third
marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome
variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in
low-resource primary healthcare settings, measurement of GGT is encouraged due to its
predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic
steatohepatitis and obesity - all known to have severe cardiovascular consequences.
Discussion and Conclusions
Excessive alcohol intake remains a major concern in the development of hypertension, CVD and
premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity,
self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers
that independently predicted 5-year change in BP, hypertension development and total mortality
in this population. Serum %CDT did not show any association with the mentioned cardiovascular
markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e.
with high GGT levels who do not consume alcohol) are typically obese women, whereas lean
men were more likely to have high alcohol consumption. Further prospective investigations are
encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting
estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly
specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in
this population also warrants further investigation. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015
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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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