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.

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.

P818Incidence of coronary heart disease in patients with familiar hypercholesterolemia compared to age- and sex- matched controls

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Svendsen ◽  
H Walaas Krogh ◽  
J Igland ◽  
K B Holven ◽  
L Mundal ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cox Regression ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
International Classification Of Diseases ◽  
Healthy Controls ◽  
Risk Of Death ◽  
Mutation Carriers ◽  
Age And Sex

Abstract Background Familial hypercholesterolemia (FH) is caused by mutations leading to high levels of low-density lipoprotein cholesterol (LDL-C) in the blood. The primary aim was to describe mutations in a large sample of individuals with FH, and compare risk of first-time hospitalization for coronary heart disease (CHD) and acute myocardial infarction (AMI) between FH mutation carriers and healthy controls. The secondary aim was to compare risk of death and re-hospitalization among FH mutation carriers and controls with a first event of CHD and AMI. Methods This study is a prospective matched cohort study comprising a sample of 5691 persons with FH and 119 511 age- and sex- matched controls randomly selected from the general Norwegian population. Information on CHD and AMI were obtained from Norwegian Patient Registry, the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry. Endpoints are defined according to the International Classification of Diseases, version 9 (ICD9) or version 10 (ICD10). Risk among persons with FH will be compared to healthy controls in terms of hazard ratios (HR) from Cox regression with follow-up time calculated from time of FH-diagnosis for the person with FH in each matched set. Results In total 51.8% (n=61866) of the combined sample were women with mean age 49.0±20.3 years, whereas 48.2% (n=57645) were men with mean age 46.8±19.6 years. There were 236 different FH mutations registered among the FH mutation carriers. The most frequent mutation was 313+1g>A, that accounted for 20.7% (n=1178) of the total, followed by C210G with 12.1% (n=690). Results for incidence of CHD, AMI, and mortality after CHD and AMI and readmission rates are not yet available but will be presented at the conference. Acknowledgement/Funding The study is funded by South-Eastern Norway Regional Health Authority

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.

scholarly journals Functional Deletion/Insertion Promoter Variants in SCARB1 Associated With Increased Susceptibility to Lipid Profile Abnormalities and Coronary Heart Disease

2022 ◽  
Vol 8 ◽  
Author(s):  
Senlin Hu ◽  
Dong Hu ◽  
Haoran Wei ◽  
Shi-yang Li ◽  
Dong Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Variants ◽  
Promoter Region ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Control Subjects ◽  
Functional Variants ◽  
Increased Risk

Background: Genetic variants in Scavenger receptor Class B Type 1 (SCARB1) influencing high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) risk were identified by recent genome-wide association studies. Further study of potential functional variants in SCARB1 may provide new ideas of the complicated relationship between HDL-C and CHD.Methods: 2000 bp in SCARB1 promoter region was re-sequenced in 168 participants with extremely high plasma HDL-C and 400 control subjects. Putative risk alleles were identified using bioinformatics analysis and reporter-gene assays. Two indel variants, rs144334493 and rs557348251, respectively, were genotyped in 5,002 CHD patients and 5,175 control subjects. The underlying mechanisms were investigated.Results: Through resequencing, 27 genetic variants were identified. Results of genotyping in 5,002 CHD patients and 5,175 control subjects revealed that rs144334493 and rs557348251 were significantly associated with increased risk of CHD [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.09 to 1.52, p = 0.003; OR: 2.65, 95% CI: 1.66–4.24, p = 4.4 × 10−5). Subsequent mechanism experiments demonstrated that rs144334493 deletion allele attenuated forkhead box A1 (FOXA1) binding to the promoter region of SCARB1, while FOXA1 overexpression reversely increased SR-BI expression.Conclusion: Genetic variants in SCARB1 promoter region significantly associated with the plasma lipid levels by affecting SR-BI expression and contribute to the susceptibility of CHD.

scholarly journals High Density Lipoprotein pathway as a therapeutic target for coronary heart disease: individual participant meta-analysis in 28,597 individuals with 4197 coronary events

2020 ◽  
Author(s):  
Amy R Mulick ◽  
David Prieto-Merino ◽  
Therese Tillin ◽  
Aki Havulinna ◽  
Martin Shipley ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
High Density Lipoprotein ◽  
Longitudinal Studies ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
High Density ◽  
Resonance Spectroscopy ◽  
Chd Risk ◽  
Increased Risk

AbstractImportanceCholesterol content in high-density lipoprotein particles (HDL-C) is associated inversely with coronary heart disease (CHD), but findings from Mendelian randomization studies and randomized trials of HDL-C raising drugs have questioned whether this link is causal. However, these analyses do not exclude a causal role for specific HDL sub-fractions of different density, mobility, size and composition.ObjectiveTo determine whether sub-components of the HDL pathway exhibit differing relationships with CHD risk.DesignIn seven longitudinal studies, we used factor analysis to reduce 21 measures of HDL particle size and lipid content to a smaller number of factors representing different components of the HDL pathway. We constructed factor scores and modelled their associations on CHD risk in adjusted Cox regression analyses. We pooled results using random-effects meta-analysis.SettingSeven population-, individual-, occupational- or community-based longitudinal studies in the UK and Finland.Participants28,597 participants (49% female, mean age 59.6 years) contributed to the analysis.ExposuresSub-components of the HDL pathway, characterized by 21 measures of HDL size and lipid content based on nuclear magnetic resonance spectroscopy.Main OutcomesIncident fatal or non-fatal CHD.ResultsWe identified 4 HDL components with highly replicable across studies; 3 were indices of particle size/composition (extra-large (XL), large (L) and medium/small (MS)), and the other an index of triglycerides (TG) carried in HDL of all sizes. After up to 17 years of follow-up, 4179 incident CHD cases occurred. After adjusting for age, sex, ethnicity, smoking, systolic blood pressure, body mass index, diabetes and LDL-C, higher levels of the XL and MS factors were linked to a reduced risk of CHD (hazard ratio per 1 standard deviation (SD) increase 0.88 [95% CI 0.85, 0.92] and 0.91 [0.87, 0.94]). In contrast, a SD increase in the level of the TG factor was associated with increased risk of CHD (1.10 [1.07, 1.14]).Conclusions and RelevanceWe found qualitative differences between sub-components of the HDL pathway and the risk of developing CHD. Discovery of the biological determinants of these components, possibly through genetic analysis, will facilitate selection of drug targets and inform trial design.Key PointsQuestionCan investigation of sub-components of the high-density lipoprotein (HDL) pathway, measured through nuclear magnetic resonance spectroscopy, point to specific therapeutic targets for prevention of coronary heart disease (CHD)?FindingsUsing individual-level data from seven longitudinal studies including 28,597 participants and 4197 CHD events, we identified two components of the HDL pathway that were associated with reduced, and one that was associated with increased, risk of CHD.MeaningThese sub-components of the HDL pathway, if causally related to atherogenesis, offer a route to more precise therapeutic targets for prevention of CHD.

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