Reversible menopause induced by the GnRH analogue buserelin: effects on lipoprotein metabolism

1992 ◽  
Vol 127 (2) ◽  
pp. 123-126 ◽  
Author(s):  
Elizabeth Farish ◽  
Colin D Fletcher ◽  
Judith F Barnes ◽  
Ann Mack ◽  
Christina E Gray ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
Hdl Cholesterol ◽  
Premature Menopause ◽  
Gnrh Analogue ◽  
Lipoprotein Subfractions ◽  
Increased Risk

GnRH agonists can induce a reversible pharmacological menopause and can be used to treat endometriosis, a fairly common gynaecological problem which responds well to oestrogen deprivation. Premature menopause is associated with adverse lipid changes and an increased risk of coronary heart disease. Therefore we set out to investigate changes in lipoprotein metabolism in a group of premenopausal women being treated with the GnRH analogue buserelin for active endometriosis. We monitored lipoprotein levels, high density lipoprotein subfractions and apolipoproteins AI, AII and B during a 12-month course of treatment and for 6 months afterwards. Treatment caused a sustained increase in HDL3 cholesterol levels and a small increase in low density lipoprotein cholesterol, which was significant at the six-month visit only. Apolipoprotein B levels rose significantly and there were marginal increases in apolipoproteins AI and AII. All changes and trends were reversed after cessation of treatment. We conclude that the treatment did not profoundly affect lipoprotein metabolism, neither LDL nor HDL cholesterol, the established important risk markers for coronary heart disease appreciably altered.

Clinical significance of lipoprotein size and risk for coronary atherosclerosis

1995 ◽  
Vol 41 (1) ◽  
pp. 147-152 ◽  
Author(s):  
P S Roheim ◽  
B F Asztalos
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Apo B ◽  
Ldl Particles ◽  
Increased Risk ◽  
Lipoprotein Size

Abstract Correlation between coronary heart disease and lipoprotein size and composition is well documented. Within the low-density lipoprotein (LDL) family the small LDL particles are associated with increased risk of coronary heart disease. These particles also have increased apolipoprotein (apo) B content. The appearance of these small LDL particles is the manifestation of complex alteration of plasma lipoprotein metabolism. The LDL size is influenced by genetic, endocrine, and environmental factors. Within the high-density lipoprotein (HDL) family the decrease of larger HDL2 particles is associated with coronary heart disease. HDLs can also be separated according to their apoprotein composition into particles containing lipoprotein (Lp)A-I only and particles containing LpA-I and LpA-II. Most studies have shown that the concentration of LpA-I-only particles decreases in coronary heart disease. HDLs are remodeled in the circulation and this remodeling continues in vitro after the blood is taken. Therefore adequate preservation of blood samples is necessary.

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

scholarly journals Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

2020 ◽  
Vol 27 (15) ◽  
pp. 1617-1626 ◽  
Author(s):  
Roshni Joshi ◽  
S Goya Wannamethee ◽  
Jorgen Engmann ◽  
Tom Gaunt ◽  
Deborah A Lawlor ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Odds Ratio ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Increased Risk ◽  
The Individual

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Gene-diet interaction and plasma lipid responses to dietary intervention

2002 ◽  
Vol 30 (2) ◽  
pp. 68-73 ◽  
Author(s):  
J. M. Ordovas
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Successful Aging ◽  
Dietary Intervention ◽  
Dietary Habits ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Dietary Recommendations ◽  
Dietary Pufa ◽  
Increased Risk

Strategies for disease prevention can have a major impact on people's health. However, major gaps exist in our knowledge with regard to nutritional adequacy, nutrient-disease interactions, nutrient-gene interactions, and effective strategies for implementation of dietary recommendations which have the potential to decrease the disease burden and to contribute to successful aging of the population. Coronary heart disease is one of the major causes of mortality in the world. We have sound evidence that high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease. Lipoprotein concentrations are associated with environmental variables such as diet and lifestyle, but genetics also play a significant role. We have examined polymorphisms at candidate loci to determine their usefulness as markers for dietary responses. A G/A polymorphism 75 bp upstream from the gene encoding apolipoprotein AI (APOA1) has been described in ~ 30% of the population. Our studies show that this polymorphism is associated with variability in the HDL-C response to dietary fat, specifically to polyunsaturated fatty acids (PUFA) in the diet. Carriers of the A allele respond to increases in dietary PUFA with elevations in HDL-C levels, probably due to altered interactions of transcription factors with the mutated promoter. Therefore carriers of the A allele can potentially decrease their atherogenic risk by consuming high-PUFA diets. Likewise, we have examined the interaction between other dietary habits, such as alcohol drinking, and variability at the APOE locus, and have demonstrated that the classical associations between APOE polymorphism and LDL-C levels are observed primarily in those subjects who consume alcohol. Moreover, we have found a subgroup of the population, APOE4 carriers, for whom drinking alcohol may exert detrimental effects on lipid metabolism. This knowledge will contribute towards the development of more effective personalized dietary recommendations.

Abstract 19: Dietary Lipophilic Load and Dietary Lipophilic Index with Risk of Coronary Heart Disease in Middle-Aged Women: Beyond Conventional Fat Classifications

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Eric L Ding ◽  
Katerina M De Vito ◽  
Hongyu Wu ◽  
Qi Sun ◽  
An Pan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Dietary Fat ◽  
Hdl Cholesterol ◽  
Health Study ◽  
Chd Risk ◽  
Increased Risk ◽  
Total Fat ◽  
Traditional Risk Factors

Introduction: Studies indicate dietary types of fats are associated with risk of coronary heart disease (CHD). Traditional broad classifications may incompletely capture the diversity of fatty acids on CHD. The novel lipid index Dietary Lipophilic Load (DLL) reflects a unique combination of fatty acid fluidity, intermolecular attraction, plus relative fat quantity, while Dietary Lipophilic Index (DLI) is a measure of average fat fluidity, regardless of fat quantity. Thus, we evaluated the association, DLL and DLI, with risk of incident CHD. METHODS: Participants included 30,932 women in the Women’s Health Study (WHS), who were free of major chronic diseases at baseline. DLL was calculated by weighted summation of the multiplicative product of each fatty acid’s intakes (g/day) and its melting points (Celcius); DLI was calculated by dividing DLL by total fat intake (g/day). Hazard ratios (HRs) were adjusted for established risk factors, with updated dietary data, and potential mediators. We also investigated hypothesized interactions with C-Reactive Protein (CRP). RESULTS: There were 1137 cases of incident CHD in 525,828 person-years over 19 years follow-up. At baseline in over 27,000 women with blood samples, DLL and DLI were not correlated with serum cholesterol, triglyceride, HbA1c, ICAM-1, or CRP biomarkers (r<0.02 for all). In overall multivariate analysis, DLL was associated with higher risk of CHD (extreme quintile HR=1.40, 95%CI: 1.11-1.76, P trend=0.0002), while DLI was not (HR=0.83, 95%CI: 0.67-1.03, P trend=0.75). DLL results were independent beyond adjustment for dietary trans, saturated, monounsaturated, and polyunsaturated fats, nor their aggregate adjustment or the P:S ratio. DLL effects persisted even adjusting for CRP (HR=1.29, P-trend=1 mg/dL for DLL (extreme quintile HR=1.38, 1.02-1.88), than among individuals with low CRP <1 mg/dl for DLL (HR=1.08, 0.68-1.72), with P-interaction<0.0001. Furthermore, CRP also modified DLI, where effects again diverged among higher CRP (HR=0.98, 0.73-1.31) versus low CRP (HR=0.45, 0.27-0.74), with P-interaction<0.0001. Moreover, adjustment of triglycerides, HbA1c, ICAM-1, LDL or HDL cholesterol also did not materially affect overall results. CONCLUSION: Results indicate that DLL is associated with increased risk of incident CHD, independent of traditional risk factors, conventional dietary fat classifications, and major CHD biomarkers. Effects of DLL and DLI appear to be modified by levels of CRP. DLL appears to be an important novel dietary fat index that captures additional CHD risk information beyond biomarkers and traditional dietary fat categories. Further studies are warranted.

Statin-treated familial hypercholesterolemia patients with coronary heart disease and pronounced atherosclerosis do not have more brain lesions than healthy controls in later middle age

2007 ◽  
Vol 48 (8) ◽  
pp. 894-899 ◽  
Author(s):  
S. Soljanlahti ◽  
R. Raininko ◽  
L. Hyttinen ◽  
K. Lauerma ◽  
P. Keto ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Familial Hypercholesterolemia ◽  
Mr Angiography ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Density Lipoprotein ◽  
Brain Lesions ◽  
Healthy Controls ◽  
Increased Risk

Background: Clinically silent brain lesions detected with magnetic resonance imaging (MRI) are associated with increased risk for stroke, while stroke risk is controversial in familial hypercholesterolemia (FH). Purpose: To determine whether the occurrence and size of clinically silent brain lesions in FH patients with coronary heart disease (CHD) is higher than in neurologically healthy controls without CHD. Material and Methods: Brain MRI (1.5T) was performed on 19 DNA-test-verified FH patients with CHD and on 29 cardiovascularly and neurologically healthy controls, all aged 48 to 64 years. All patients were on cardiovascular medication. Intracranial arteries were evaluated by MR angiography. Infarcts, including lacunas, and white matter T2 hyperintensities (WMHI), considered as signs of small vessel disease, were recorded. A venous blood sample was obtained for assessment of risk factors. Carotid and femoral intima-media thicknesses (IMT), assessed with ultrasound, were indicators of overall atherosclerosis. Results: On intracranial MR angiography, three patients showed irregular walls or narrowed lumens in intracranial carotid arteries. No silent infarcts appeared, and no differences in numbers or sizes of WMHIs between groups were recorded. Patients had greater carotid and femoral IMTs, and a greater number of carotid and femoral plaques. Cholesterol-years score, level of low-density lipoprotein (LDL) cholesterol, and level of high-sensitivity C-reactive protein (hsCRP) of the FH-North Karelia patients were higher than those of the controls, while the level of high-density lipoprotein (HDL) cholesterol in controls was higher. Conclusion: FH patients with CHD and adequate cardiovascular risk-factor treatment showed no difference in the amount or size of clinically silent brain lesions compared to controls, despite patients' more severe atherosclerosis.

Association between both lipid and protein oxidation and the risk of fatal or non-fatal coronary heart disease in a human population

2008 ◽  
Vol 116 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Mark Woodward ◽  
Kevin D. Croft ◽  
Trevor A. Mori ◽  
Henrietta Headlam ◽  
Xiao Suo Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Plasma Samples ◽  
Stable Isotope Dilution ◽  
Fatal Coronary Heart Disease ◽  
Independent Association ◽  
And Gender ◽  
Nested Case Control

The role of oxidative damage in the aetiology of coronary disease remains controversial, as clinical trials investigating the effect of antioxidants have not generally been positive. In the present study, 227 coronary cases, identified from a cohort study, were matched, by age and gender, with 420 controls in a nested case-control design. Stored plasma samples were analysed for F2-isoprostanes by stable isotope dilution MS, and specifically oxidized forms of apoA-I (apolipoprotein A-I) by HPLC of HDL (high-density lipoprotein). Median values of F2-isoprostanes were higher in plasma samples that contained oxidized apoA-I compared with samples with undetectable oxidized apoA-I (1542 compared with 1165 pmol/l). F2-Isoprostanes were significantly correlated with variants of non-oxidized apoA-II (r=−0.15) and were associated with HDL-cholesterol (P<0.0001). F2-Isoprostanes in cases (median, 1146 pmol/l) were not different from controls (1250 pmol/l); the odds ratio (95% confidence interval) for a 1 S.D. increase in F2-isoprostanes was 1.08 (0.91–1.29). Similarly, there was no independent association between the presence of oxidized apoA-I, detected in approx. 20% of the samples, and coronary risk. In conclusion, we found no evidence of associations between markers of lipid (F2-isoprostanes) and protein (oxidized apoA-I) oxidation and the risk of fatal or non-fatal coronary heart disease in a general population. This may be due to a true lack of association or insufficient power.

Risk Factor Variability and Coronary Heart Disease

1990 ◽  
Vol 39 (1) ◽  
pp. 15-24 ◽  
Author(s):  
K. Berg
Keyword(s):  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Absolute Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Protein Product ◽  
Risk Factor Level ◽  
Gene Effect

AbstractPresent attempts to identify genes contributing to coronary heart disease (CHD) risk focus on “candidate genes”. With respect to CHD this could be any gene whose protein product is directly or indirectly involved in atherogenesis, thrombogenesis or thrombolysis/fibrinolysis. Genes that exhibit associations with absolute risk factor levels may be referred to as “level genes” to distinguish them from “variability genes”, which are genes involved in establishing the framework within which environmental influences may cause risk factor variation. In a series of persons recruited from the Norwegian Twin Panel, confirmatory evidence for level gene effect with respect to apolipoprotein B (apoB) concentration was found with an XbaI polymorphism in DNA at the apoB locus corresponding to residue 2,488 in the mature protein. Evidence for variability gene effect with respect to apoB as well as body mass index emerged with DNA variants in the 3′ part of the apoB gene. Level gene effect with respect to apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) cholesterol as well as apparent variability gene effect with respect to total and LDL cholesterol were detected with a DNA polymorphism at the cholesteryl ester transfer protein (CETP) locus. The first example of interaction between normal genes in determining risk factor level was uncovered in analysis of the apolipoprotein E (apoE) polymorphism and a restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus. An LDLR gene identified by presence of a PvuII restriction site eliminated completely the well known effect of the apoE4 allele on cholesterol level. Finally, in families where high Lp(a) lipoprotein level (a well established risk factor for CHD) segregated as a Mendelian trait, very close linkage with an RFLP at the plasminogen locus was established and DNA variation at the LPA locus reflecting varying numbers of a structure homologous to the “kringle IV” region of plasminogen was uncovered.

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