Onset Of Coronary Heart Disease Research Articles

Crossing family histories of diabetes and cardiovascular disease leads to unexpected outcomes in diabetic offspring.

This study investigated the isolated and crossed effects of familial histories (FH) of early onset coronary heart disease (EOCHD) and type 2 diabetes mellitus (T2DM) on diabetic offspring. The cardiometabolic phenotype of 1098 T2DM patients was analyzed according to an FH of T2DM and/or EOCHD, including body composition, fasting insulinemia, insulin sensitivity, β-cell function (BCF), lipids, lipoprotein(a), high-density lipoprotein (HDL) number and functionality, and micro- and macrovascular complications. Mean age and T2DM duration were 69 and 18 years, respectively; 64% of patients were male, 50% (n = 550) had an FH of T2DM (DM[+]), and 13% (n = 145) had an FH of EOCHD (EOCHD[+]). Four subgroups were generated by crossing FHs: DM[-]EOCHD[-] (44%; n = 487); DM[+]EOCHD[-] (42%; n = 466); DM[-]EOCHD[+] (6%; n = 61); and DM[+]EOCHD[+] (8%; n = 84). Microangiopathies were highest among DM[+] patients, whose BCF was deteriorating the fastest. More numerous/dysfunctional HDLs characterized EOCHD[+] patients. The greatest frequency of cardiovascular disease (CVD; 69%) was observed in DM[-]EOCHD[+] patients, whose lipoprotein(a) and insulinemia were also highest (81 nmol/L and 140 pmol/L, respectively). The lowest frequency of CVD (30%) was observed in DM[+]EOCHD[-] patients. Familial histories of DM and EOCHD predispose to increased microvascular and macrovascular risk, respectively, with hyperinsulinemia, lipoprotein(a), and dysfunctional HDLs standing out as mediators of the inherited macrovascular risk. Yet, crossing these FHs did not randomly redistribute vascular risk, because patients with parental T2DM had fewer macrovascular diseases regardless of familial EOCHD. The odds of being left-handed were unexpectedly greater in patients with crossed parental histories.

Association of longitudinal alcohol consumption trajectories with coronary heart disease: a meta-analysis of six cohort studies using individual participant data

BackgroundStudies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD.MethodsData were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants’ intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics.ResultsCompared to consistently moderate drinkers (males: 1–168 g ethanol/week; females: 1–112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02–1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13–1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21–1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors.ConclusionsUsing prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake.Trial registrationClinicalTrials.gov, NCT03133689.

Atherosclerotic plaque in carotid arteries as a risk marker for cardiovascular events risk in middle aged population

Aim. To reveal the associations of carotid arteries atherosclerosis severity and cardiovascular events in mostly middle aged population. Material and methods . In the study, 1100 persons participated of the ATHEROGEN-Ivanovo trial (substudy of ESSE-RF), age 40-67 y. o. All participants underwent duplex scan of carotid arteries (Samsung Medison MySono U6) with assessment of the number of atherosclerotic plaques (AP), maximum stenosis and total stenosis with calculation of gender-specific quintiles. With the Cox regression model, risk was estimated for combinatory endpoint including all-cause death, myocardial infarction, novel onset of coronary heart disease, stroke, any area revascularization. Median follow-up 3,8 years. Results. The AP were found in 74,5% males and 58,0% females. In males atherosclerosis was more severe: maximum stenosis 27 (0-34)% in males vs 22 (0-58)% in females (р<0,001), total stenosis — 48 (0-90)% vs 22 (0-31)% (р<0,001) and plaques number — 2 (0-3) vs 1 (0-2) (р=0,000). There were 24 endpoints documented. 23 of 24 endpoints occurred in persons with at least any ultrasound marker value within quintile ≥3. Regression showed that if at least one ultrasound marker should have reached the quintile ≥3 (e. g., maximum stenosis ≥25% in men), than the risk of events from combinational endpoint would increase 8,5 times — 95% CI 1,12-64,76 (p=0,039). Also, coronary heart disease increases the risk 4,05 times — 95% CI 1,46-11,21 (p=0,007), acute stroke 3,49 times — 95% CI 1,19-10,23 (p=0,023). The number of males with AP <25% was 15%. Conclusion. The presence of AP in carotid arteries does 8,5 times increase the risk of cardiovascular events, and for 15% of males in population with AP in carotid arteries that narrow the lumen <25%, it is needed to clarify the risk.

THE CORRELATION OF OBESITY INDEX AND THE LEVEL OF TRIGLYCERIDE IN VILLAGERS

The obesity index is a parameter that describes general and central obesity. Obesity prevalence tends to increase in the rural areas of Indonesia. The increased prevalence of obesity is correlated with increased cardiovascular prevalence and diabetes. Dyslipidemia is also a risk factor for cardiovascular disease and is closely related to obesity. Obesity is an accumulation of excessive triglyceride levels and stored in adipose tissue that can contribute to the onset of coronary heart disease. This was an analytical observational study with a cross-sectional design. Research subjects were the rural community in Bonjoroyo village, Kulonprogo Regency, DIY which fulfilled the inclusion criteria. The data obtained were obesity index data (Body Mass Index/BMI, Waist Circle/LP, Waist Round/RLPP Ratio, Body Waist Ratio/RLPTB) and triglyceride levels which were then analyzed statistically with normality test and continued with correlation Spearman test with a 95% confidence level. The results showed that BMI, LP, and RLPTB measurements were significantly positively correlated with moderate-to-weak correlation strength in fasting blood triglyceride levels (r:0.435; p:0.000; r:0.362; p:0.002; r:0.347; p:0.004) in males. Measurements of BMI, LP, and RLPTB were positively correlated with a weak correlation strength against fasting blood triglyceride levels (r: 0.193; p: 0.028; r: 0.226; p: 0.010; r: 0.214; p: 0.014) in females. The RLPP obesity index did not show significant correlations to fasting triglyceride levels in rural communities.

Genetic diagnosis of familial hypercholesterolemia is associated with a premature and high coronary heart disease risk.

Familial hypercholesterolemia (FH) is a common autosomal dominant disease associated with premature coronary heart disease (CHD). Studies tend to show that patients with FH associated with an identified mutation (mutation+ FH) are at higher risk than patients without an identified mutation (mutation- FH). We compared the clinical and biological profile and the risk of CHD in patients with mutation+ FH and mutation- FH. In addition to LDL-C, a pathogenic mutation predicts premature CHD in FH. We successively included all patients with suspected FH (LDL-C > 190 mg/dL if age > 18 years; LDL-C > 160 mg/dL if age < 18 years) and compared patients with a pathogenic mutation with those without an identified pathogenic mutation. We studied 179 patients with mutation+ FH and 147 with mutation- FH. The mean age was 44 (± 18) years. The lipid profile was more atherogenic in those with mutation+ FH, who had higher LDL-C (254 ± 69 mg/dL vs 218 ± 35 mg/dL; P < 0.01) and lower HDL-C (53 ± 14 mg/dL vs 58 ± 17 mg/dL; P < 0.01). Despite the more atherogenic nonlipid cardiovascular profile of patients with mutation- FH, the age of CHD onset was earlier in patients with mutation+ FH (48 vs 56 years; P = 0.026). After multiple adjustment, the presence of a positive mutation was significantly associated with premature CHD (OR: 3.0, 95% CI: 1.38-6.55, P < 0.01). Patients with mutation+ FH have a more atherogenic lipid profile and a 3-fold higher risk of premature CHD, as well as earlier onset of CHD, than patients with mutation- FH.

Integrated genetic and epigenetic prediction of coronary heart disease in the Framingham Heart Study.

An improved method for detecting coronary heart disease (CHD) could have substantial clinical impact. Building on the idea that systemic effects of CHD risk factors are a conglomeration of genetic and environmental factors, we use machine learning techniques and integrate genetic, epigenetic and phenotype data from the Framingham Heart Study to build and test a Random Forest classification model for symptomatic CHD. Our classifier was trained on n = 1,545 individuals and consisted of four DNA methylation sites, two SNPs, age and gender. The methylation sites and SNPs were selected during the training phase. The final trained model was then tested on n = 142 individuals. The test data comprised of individuals removed based on relatedness to those in the training dataset. This integrated classifier was capable of classifying symptomatic CHD status of those in the test set with an accuracy, sensitivity and specificity of 78%, 0.75 and 0.80, respectively. In contrast, a model using only conventional CHD risk factors as predictors had an accuracy and sensitivity of only 65% and 0.42, respectively, but with a specificity of 0.89 in the test set. Regression analyses of the methylation signatures illustrate our ability to map these signatures to known risk factors in CHD pathogenesis. These results demonstrate the capability of an integrated approach to effectively model symptomatic CHD status. These results also suggest that future studies of biomaterial collected from longitudinally informative cohorts that are specifically characterized for cardiac disease at follow-up could lead to the introduction of sensitive, readily employable integrated genetic-epigenetic algorithms for predicting onset of future symptomatic CHD.

Effects of the polymorphisms in ABCG1 gene on the transcription activity and the susceptibility with coronary artery disease.

Objective To investigate the effects of the polymorphisms in the promoter of ATP binding cassette transporter (ABCG1) on the transcription activity, and the relationship of the polymorphisms with the susceptibility to coronary artery disease (CAD). Methods A case-control study was conducted, 217 CADpatients and 142 controls were enrolled in this study.Thesingle nucleotide polymorphisms (SNPs) in the promoter of ABCG1 were identified by sequencing.The promoter haplotypes of ABCG1 were determined with allele specific primer sequencing or Gene cloning sequencing.The transcription activity of the promoter haplotypes were evaluated with dual luciferase reporter system.The frequency of SNPs and haplotypes were analyzed between CAD group and the control group, premature CAD and non-premature CAD group, as well as multivessel lesion and single vessel lesion group. The frequency distribution was compared between two groups with χ2 test or Fisher exact test. The difference of the luciferase activity was compared between groups by t-test or one-way analysis of variance. Results Only 3 SNPs were found in ABCG1 promoter sequence of about 1 000 bp upstream of the transcription start site, which are -384(A/G), -204(A/C) and -134(T/G), respectively.The 3 SNPs are in strong linkage disequilibrium, Tajima’s D = 2.655 (P<0.01), which constituted 3 haplotypes. There was no significant difference in SNPs and haplotype frequency between the CAD group and the normal control group, and the severity of vascular disease and the early onset of coronary heart disease were not associated with the polymorphisms in ABCG1 promoter.There was no significant difference in the transcriptional activity of the three constitutive promoter haplotypes, but the transcriptional activity was notably elevated as the GAT haplotype was mutated into GAG (P<0.05). Conclusions The 3 SNPs identified in ABCG1 promoter region A did not alter the promoter activity.There was no significant correlation between the frequency distribution of SNPs and promoter haplotypes and the susceptibility to CAD. Key words: Coronary atherosclerotic disease; ATP binding cassette transporter G1; Promoter; Single nucleotide polymorphisms; Haplotype; Linkage disequilibrium; Gene cloning; Dual luciferase reporter system

The role of registries and genetic databases in familial hypercholesterolemia.

To review how leveraging familial hypercholesterolemia registries can impact molecular genetic research and precision medicine. Familial hypercholesterolemia is both much more common and more phenotypically heterogeneous than previously thought with some evidence for significant genotype to phenotype correlations. Genetic testing for familial hypercholesterolemia is becoming both more widely available and cheaper, spurring conversations about its clinical utility. In most countries, familial hypercholesterolemia is underdiagnosed and diagnosed later in life, often after the onset of coronary heart disease (CHD). Familial hypercholesterolemia is undertreated; low goal attainment and additional modifiable risk factors further increase CHD risk. Familial hypercholesterolemia epitomizes the goal of precision medicine to define a subset of individuals with a high risk of morbidity and mortality through genetic diagnosis to manage and treat the risk accordingly. Genetic cascade screening can be used to identify familial hypercholesterolemia patients at a younger age and start timely treatment to prevent CHD. Familial hypercholesterolemia registries are tools for clinical research and improving healthcare planning and patient care. As genotype and phenotype correlations in familial hypercholesterolemia become increasingly understood, this information will likely play a more important role in diagnosis and treatment especially as the cost of genetic testing continues to decline.

Parental-Offspring Association of Age of Onset of Coronary Heart Disease or Stroke A Prospective Cohort Study of Parents and Offspring

International Journal of Medicine and Public Health,2017,7,1,23-27.DOI:10.5530/ijmedph.2017.1.3Published:March 2017Type:Original ArticleParental-Offspring Association of Age of Onset of Coronary Heart Disease or Stroke A Prospective Cohort Study of Parents and OffspringNessim Abu Saif, Shannon A. Allport, Ngum Kikah, and Folefac D. Atem Nessim Abu Saif1,2*, Shannon A. Allport1,3*, Ngum Kikah1, Folefac D. Atem1 1The University of Texas Health Science Center School of Public Health, Dallas, Texas, United States of America 2Trinity School of Medicine, Kingstown, St. Vincent and the Grenadines 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. Abstract:Objective: To investigate the effect of parental age of onset of coronary heart disease (chd) or stroke on age of onset of chd or stroke in offspring. Design: Inception cohort study. Methods: The association between age of onset of chd or stroke in offspring and maternal age of onset of chd or stroke and the association between age of onset of chd or stroke in offspring and paternal age of onset of chd or stroke were assessed using the cox proportional hazard model after conditionally imputing the censored parents (i.E. Parents who did not experience chd or stroke during the study). Results: Parental age of onset of chd was predictive of offspring age of onset of chd for both maternal age of onset of chd (p < 0.0001 N=1378) and for paternal age of onset of chd (p=0.0005 N=1194). A negative estimate of the coefficient of interest signifies that late onset of coronary heart disease in parents is protective of onset of chd in offspring. Beer intake and hdl were important confounding variables associated with parental and offspring age of onset chd. Conclusion: Using cox proportional hazard model, we found that late onset of chd or stroke in parents is cardioprotective for offspring. Parental age of onset of chd or stroke is associated with offspring age of onset of chd, and this relationship is described for each unit increase or decrease of age of onset using these statistical methods. This relationship suggests that data on parental history can be useful in the clinical setting in the determination of risk among those at intermediate levels of predicted risk using existing risk calculators. Keywords:cardiovascular disease, cerebrovascular accident, coronary heart disease, onset of cardiovascular disease, risk factor, strokeView:PDF (217.52 KB) Full Text

Assessment of lipid profile and some risk factors of atherosclerosis in children whose parents had early onset coronary artery disease.

The objective of our study was to analyze the lipid profile and some risk factors of atherosclerosis such as oxidized-low density lipoprotein (ox-LDL), small dense LDL (sd LDL) in the offspring of patients with premature coronary heart disease (CHD). Children whose parents had early onset CHD were matched with age and sex pairs. Study and controls were analyzed for lipid levels, apolipoproteins (Apo- A,B,E), ox-LDL, sd LDL and lipoprotein (a) [Lp(a)]. The data were evaluated with SPSS using "Student t and Mann-Whitney U" tests. The study group children (n: 43) had higher LDL, Lp(a) and ox-LDL levels, ratios of TC/HDL, Apo-B/A, LDL/HDL and ox-LDL/HDL (p<0.05) than control group. These findings suggest that dyslipidemia and increased LDL, Lp(a) and ox-LDL levels are common in the offspring of patients with early onset CHD and account largely for their familial predisposition for CHD.

Body size at birth and coronary heart disease-related hospital care in adult men – findings from the Helsinki Birth Cohort Study

Aim: We investigated, among those who had been hospitalized at least once due to coronary heart disease (CHD), the relationship between ponderal index (PI, birthweight/length3) at birth, a measure of thinness, and the age at first hospitalization due to CHD, the number of CHD-related hospital care episodes, and cost of CHD-related hospital care from young adulthood to old age.Methods and results: Data from the Helsinki Birth Cohort Study included 964 men born in Helsinki, Finland during 1934–1944, who had been hospitalized due to CHD and had birth anthropometrics data. PI (kg/m3) was categorized into low (<25.0), medium (25.0–27.5), and high (>27.5). CHD-related hospital care data were available from 1971 to 2013. We observed an earlier onset of (p = .014 for linearity) and a higher rate of CHD-related hospital care episodes among those in the lowest PI group (incidence rate ratio: 1.35 [95% confidence interval: 1.16–1.59, p < .001]), compared to the highest PI group. CHD-related hospital care costs in the lowest PI group were 25% (p = .001, 4% to 46%) higher compared to those in the highest PI group.Discussion: Thinness at birth is associated with earlier onset, higher prevalence, and higher accumulated costs of CHD-related hospital in-patient care among men who developed CHD.KEY MESSAGESFindings from this large birth cohort indicate that the onset of coronary heart disease (CHD)-related hospital in-patient care occurred at younger age during the 42-year time period among men who were born thin.Lower ponderal index (PI) was associated with a higher rate of CHD-related hospital in-patient care during the time period. We observed a linear increase in CHD-related hospital in-patient care costs across PI groups.

Increased serum levels of interleukin 1 receptor antagonist (IL-1ra) levels precede the onset of coronary heart disease: results from the MONICA/KORA Augsburg study

Aims: Interleukin-1β (IL-1β) represents a key proinflammatory cytokine in the development of atherosclerosis and coronary heart disease (CHD). The activity of IL-1β is counter-regulated by interleukin-1 receptor antagonist (IL-1ra), an endogenous inhibitor. Data on the relevance of circulating IL-1ra levels for cardiovascular risk are scarce and inconsistent. Therefore, this study aimed (i) to examine the association between serum IL-1ra and incident CHD in the general population and (ii) to test whether this association is explained by other inflammation-related biomarkers. Methods: This case-cohort study uses data from the population-based MONICA/KORA Augsburg cohort. During a follow-up time of 16.0 ± 5.8 years, 803 cases and 1942 non-cases were observed for the combined CHD endpoint (non-fatal myocardial infarction and coronary death before the age of 75 years). Associations between IL-1ra and incidence of CHD were assessed using Cox regression adapted for cases-cohort analyses. Results: Cases had higher IL-1ra serum levels than non-cases (geometric means [antilog of SE] 338.81 [1.02] vs. 352.59 [1.01] pg/ml; p < 0.001). The hazard ratio (95% CI) for incident CHD was 1.15 (1.02; 1.30) per standard deviation of log-transformed IL-1ra serum levels after adjustment for age, sex, anthropometric, metabolic and lifestyle factors (p = 0.022). The excess risk for CHD was attenuated by ≥10% after additional adjustment for high-sensitivity C-reactive protein, IL-6, myeloperoxidase or soluble adhesion molecules. Conclusion: Serum IL-1ra levels are positively associated with increased risk of CHD. This association may at least partially reflect a counter-regulation to subclinical inflammation, endothelial activation and oxidative stress.

Effect of Cytochrome P450 2C19 681G&gt;A Polymorphism on Premature Coronary Heart Disease

Objective: The aim of our study was to evaluate the association between cytochrome P450 2C19 (CYP2C19) 681G>A polymorphisms and the age of development of coronary heart disease. Additionally, the study might find some biological indicators at the gene level that could help to predict and evaluate the risk of coronary heart disease in time. Methods: This study included 352 individuals with coronary heart disease. Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) was used to identify CYP2C19 681G>A. The objects were divided into wild type (GG or homozygous CYP2C19*1 wild-type) and mutant type (GA/AA or the mutant CYP2C19*2 allele) on the basis of genotype. The association between CYP2C19 gene polymorphism and the age of onset of coronary heart disease was assessed by multivariate linear regression analysis. Results: There was a significant association in the age of onset between the two groups (t=3.398, P=0.001), which was 58.51±12.72 years in the wild type and 53.95±11.63 years in the mutant group. The frequency of CYP2C19 681A (CYP2C19*2 allele) was 0.32, 0.268, 0.227 in different age groups, which was significantly different (χ 2 =10.745, P=0.005) in different groups, as well as in the genotype. The result, assessed by multiple linear regression, showed that genotype, smoking, obesity, and hyperlipidemia affect the age of onset of coronary heart disease (β was -0.167, 0.156, 0.155, and 0.112, P A gene polymorphism may be one of the risk factors in susceptibility to early onset of coronary heart disease, but not an independent factor because other factors may play a synergistic role.

Correlation of androgenetic alopecia and early onset coronary heart disease in men.

Correlation of androgenetic alopecia and early onset coronary heart disease in men.

Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C.

Analyses using conventional statistical methodologies have yielded conflicting results as to whether low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) is the best marker of the apoB-associated risk of coronary heart disease. The aim of this study was to determine the additional value of apoB beyond LDL-C or non-HDL-C as a predictor of coronary heart disease. For each patient from the Framingham Offspring Cohort aged 40-75 years (n = 2966), we calculated the extent to which the observed apoB differed from the expected apoB based on their LDL-C or non-HDL-C. We added this difference to a Cox model predicting new onset coronary heart disease over a maximum of 20 years adjusting for standard risk factors plus LDL-C or non-HDL. The difference between observed and expected apoB over LDL-C or non-HDL-C was highly prognostic of future coronary heart disease events: adjusted hazard ratios 1.26 (95% confidence interval: 1.15, 1.37) and 1.20 (1.11, 1.29), respectively, for each standard deviation increase beyond expected apoB levels. When this difference between observed and expected apoB was added to standard coronary heart disease prediction models including LDL-C or non-HDL-C, prediction improved significantly (likelihood ratio test p-values <0.0001) and discrimination c-statistics increased from 0.72 to 0.73. The corresponding relative integrated discrimination improvements were 11% and 8%, respectively. apoB improves risk assessment of future coronary heart disease events over and beyond LDL-C or non-HDL-C, which is consistent with coronary risk being more closely related to the number of atherogenic apoB particles than to the mass of cholesterol within them.

Onset of Coronary Heart Disease and Urban Residential Noise

Onset of Coronary Heart Disease and Urban Residential NoiseAbstract Number:1732 Audrey Smargiassi *, Claudia Blais, Philippe Gamache, Sophie Goudreau, and Larisa-Ines Yankoty Audrey Smargiassi * Département de santé environnementale et de santé au travail, Université de Montréal, Canada, E-mail Address: [email protected] Search for more papers by this author , Claudia Blais Institut national de santé publique du Québec, Canada, E-mail Address: [email protected] Search for more papers by this author , Philippe Gamache Institut national de santé publique du Québec, Canada, E-mail Address: [email protected] Search for more papers by this author , Sophie Goudreau Montreal Public Health, Canada, E-mail Address: [email protected] Search for more papers by this author , and Larisa-Ines Yankoty University of Montreal, CANADA Search for more papers by this author AbstractBackground: There is increasing evidence on the cardiovascular effects of transportation noise in European countries, but a notable paucity of studies from other countries such as those in North America. Yet differences in house construction related to insulation from colder climate or in people’s habits such as window opening may affect exposure levels of the occupants and modify associations seen in Europe and elsewhere. Objective: To examine the association between the onset of coronary heart disease (CHD) in adults and residential exposure to urban noise in Montreal, Canada.Methods: Using linked administrative health databases, we identified all individuals aged = 45 years living on the Island of Montreal and who had not move since 2005. We estimated residential noise exposure in 2010 (LAeq24h) using a Land Use Regression model. Cases of CHD that occurred in 2010 were identified using a validated algorithm based on hospitalization and physician billing claims. A logistic regression was used to estimate the association between residential noise exposure and CHD onset, adjusting for age, sex and a deprivation index.Results: There were 434,433 individuals aged = 45, free of CHD and who had lived since 2005 at the same address. Their mean LAeq24h was 61.0 dB(A) (Standard Deviation : 3.9 dB(A)). 5316 individuals developed CHD in 2010. The crude odds of CHD onset in 2010 was 1.34 (95 % CI: 1.26-1.44) per increase of 10 dB(A) while the adjusted OR was 1.07 (1.00-1.15).Conclusions: These preliminary results reinforce that exposure to urban noise is associated with the onset of CHD.

Daily life, experience and needs of persons suffering from homozygous familial hypercholesterolaemia: Insights from a patient survey

Homozygous familial hypercholesterolaemia (HoFH) is a rare and severe hereditary lipid disorder that is typically associated with high serum levels of low-density lipoprotein cholesterol (LDL-C). Excessive exposure to high levels of LDL-C puts affected individuals at very high risk of premature onset coronary heart disease, and this considerably limits life expectancy. Although the clinical features and treatment of HoFH have been extensively researched, societal and socio-psychological impacts of the disease have not been reported to date. The current study was conducted to investigate the burden of disease and treatment from the patient's perspective by means of semi-structured interviews with 24 HoFH patients. The findings of the survey indicate that HoFH represents a considerable burden for patients, not only due to physical signs and limitations caused by the disease but also a number of psychosocial factors, treatment-related issues and impact on their education and employment situation.

Familial hypercholesterolemia: developments in diagnosis and treatment.

Familial hypercholesterolemia (FH) is a congenital disorder of lipid metabolism characterized by a marked elevation of the plasma concentration of LDL (low-density lipoprotein) cholesterol beginning in childhood and by the early onset of coronary heart disease. It is among the commonest genetic disorders, with an estimated prevalence in Germany of at least 1 per 500 persons. Review of pertinent literature retrieved by a selective search. FH is underdiagnosed and undertreated in Germany. It is clinically diagnosed on the basis of an elevated LDL cholesterol concentration (>190 mg/dL [4.9 mmol/L]), a family history of hypercholesterolemia, and early coronary heart disease, or the demonstration of xanthomas. The gold standard of diagnosis is the identification of the underlying genetic defect, which is possible in 80% of cases and enables the identification of affected relatives of the index patient. The recommended goals of treatment, based on the results of observational studies, are to lower the LDL cholesterol concentration by at least 50% or to less than 100 mg/dL (2.6 mmol/L) (for children: <135 mg/dL [3.5 mmol/L]). The target value is lower for patients with clinically overt atherosclerosis (<70 mg/dL [1.8 mmol/L]). Statins, combined with a health-promoting lifestyle, are the treatment of choice. Lipoprotein apheresis is used in very severe cases; its therapeutic effects on clinical endpoints and its side effect profile have not yet been documented in randomized controlled trials. Familial hypercholesterolemia is a common disease that can be diagnosed simply and reliably on clinical grounds and by molecular genetic testing. Timely diagnosis and appropriate treatment can lower the risk of atherosclerosis in heterozygous patients to that of the general population.

Trauma exposure and the subsequent risk of coronary heart disease among mid-aged women.

The objective of the current study was to examine whether exposure to trauma in the form of a history of physical, mental, emotional or sexual abuse or violence predicted new onset of coronary heart disease (CHD) in women. In addition, this study aimed to examine the mediation effects of psychological, lifestyle and health related factors in the abuse-CHD relationship. Data from 6 surveys over 15 years, from the Australian Longitudinal Study on Women's Health, a large prospective cohort study, were used. Participants from the 1946-1951 cohort who did not self-report heart disease at surveys 1 (1996) and 2 (1998) and who had provided information on other variables were included (n = 9,276). After adjusting for age, women who reported trauma exposure at baseline were 1.54 times more likely (95% confidence interval 1.29-1.83) to report new onset of CHD than those who did not report trauma exposure. The association between trauma and CHD was largely explained by psychological factors, suggesting a direct pathway between exposure to trauma and risk of CHD.

Cascade screening based on genetic testing is cost-effective: evidence for the implementation of models of care for familial hypercholesterolemia.

Familial hypercholesterolemia (FH) imposes significant burden of premature coronary heart disease (CHD). This study aimed to determine the cost-effectiveness of FH detection based on genetic testing, supplemented with the measurement of plasma low-density lipoprotein cholesterol concentration, and treatment with statins. A Markov model with a 10-year time horizon was constructed to simulate the onset of first-ever CHD and death in close relatives of probands with genetically confirmed FH. The model comprised of 3 health states: "alive without CHD," "alive with CHD," and "dead." Decision-analysis compared the clinical consequences and costs of cascade-screening vs no-screening from an Australian health care perspective. The annual risk of CHD and benefits of treatment was estimated from a cohort study. The underlying prevalence of FH, sensitivity, specificity, cost of screening, treatment, and clinic follow-up visits were derived from a cascade screening service for FH in Western Australia. An annual discount rate of 5% was applied to costs and benefits. The model estimated that screening for FH would reduce the 10-year incidence of CHD from 50.0% to 25.0% among people with FH. Of every 100 people screened, there was an overall gain of 24.95 life-years and 29.07 quality-adjusted life years (discounted). The incremental cost-effectiveness ratio was in Australian dollars, $4155 per years of life saved and $3565 per quality-adjusted life years gained. This analysis within an Australian context, demonstrates that cascade screening for FH, using genetic testing supplemented with the measurement of plasma low-density lipoprotein cholesterol concentrations and treatment with statins, is a cost-effective means of preventing CHD in families at risk of FH.