Early-onset Coronary Heart Disease Research Articles

Plasma protein profile associated with a family history of early-onset coronary heart disease

Abstract Introduction Although family history of coronary heart disease (CHD) is an established risk factor for subsequent CHD, its relation to the circulating proteome is unknown. Proteins linked to coronary atherosclerosis in subjects with a family history could uncover new pathophysiological mechanisms of heritable CHD. Purpose Firstly, we aimed to study the protein profile associated with a family history of early-onset CHD. Secondly, we aimed to identify proteins among which family history was an effect modifier for the association between each protein and coronary atherosclerosis. Methods Plasma levels of proteins were assessed with Olink panels CVD-II and -III in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. The coronary segment involvement score (SIS) was assessed from computed tomography angiography. Subjects without known CHD were cross-referenced with national registers to identify records of myocardial infarction or coronary revascularization in any parent before 55 or 65 years of age in males and females, respectively. The associations between a family history of CHD and each protein were studied with linear regression adjusted for age, sex and study site, using a False Discovery Rate (FDR) of 5%. Associations were subsequently adjusted for cardiovascular risk factors. Similarly, associations between each protein and SIS were modelled linearly with an FDR of 5%. For significant proteins, the statistical interactions between each protein and family history for the association between proteins and SIS were studied. Results Of 4,251 subjects, 9.5% had a family history CHD. 43 proteins were significantly associated with family history, and when adjusted for risk factors 29 protein associations remained significant (p<0,05) [Figure 1]. The strongest associations were observed for cathepsin D, paraoxonase 3, interleukin-1 receptor antagonist protein and renin. 79 proteins were associated with SIS at FDR<5%, and family history was a significant effect modifier 18 for proteins [Figure 2]. The strongest modifying effects were observed for transferrin receptor protein 1 (β 0.64, 95% CI 0.25–1.04 for those with family history vs β -0.04, 95% CI -0.14–0.06 in those without, p for interaction=0.001), LDL-receptor (β 0.68, 95% CI 0.36–1.00 vs β 0.18, 95% CI 0.08–0.26) and tissue-type plasminogen activator (β 0.45, 95% CI 0.19–0.70 vs β 0.13, 95% CI 0.05–0.21). Conclusion We found that 43 proteins, with biological features of inflammation and vascular function, were associated with a family history of early-onset CHD. Most were also linked to the coronary atherosclerosis burden. Notably, 18 biomarkers, among them transferrin receptor protein 1, LDL-receptor and tissue-type plasminogen activator, exhibited strong statistical interactions with family history in the association with SIS, indicating that they are of particular importance for the genetic susceptibility and the pathophysiology of heritable CHD.

Research Progress in the Clinical Treatment of Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease with severe disorders of lipid metabolism. It is mainly marked by increasing levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), xanthoma, corneal arch, and early-onset coronary heart disease (CHD). The prevalence of FH is high, and it is dangerous and clinically underdiagnosed. The clinical treatment for FH includes both pharmacological and non-pharmacological treatment, of which non-pharmacological treatment mainly includes therapeutic lifestyle change and dietary therapy, LDL apheresis, liver transplantation and gene therapy. In recent years, many novel drugs have been developed to treat FH more effectively. In addition, the continuous maturity of non-pharmacological treatment techniques has also brought more hope for the treatment of FH. This paper analyzes the pathogenic mechanism and the progress in clinical treatment of FH. Furthermore, it also summarizes the mechanism and structure-activity relationship of FH therapeutic drugs that have been marketed. In a word, this article provides a reference value for the research and development of FH therapeutic drugs.

Polygenic risk scores for complex diseases: Where are we now?

Polygenic risk scores for complex diseases: Where are we now?

Oxidized phospholipids on apolipoprotein B-100 versus plasminogen and risk of coronary heart disease in the PROCARDIS study

Background and aimsOxidized phospholipids carried on the apolipoprotein B-100 (OxPL-apoB) component of Lp(a) are predictive of coronary heart disease (CHD), but the role of oxidized phospholipids carried on plasminogen (OxPL-PLG) is unknown. We examined the independent effects of OxPL-apoB and OxPL-PLG for risk of CHD before and after adjustment for Lp(a). MethodsPlasma levels of OxPL-apoB, OxPL-PLG, plasminogen and Lp(a) were measured in the PROCARDIS study of early-onset CHD (906 cases/858 controls). Multivariable logistic regression was used to estimate the odds ratios (OR) for each biomarker with CHD after adjustment for established risk factors. ResultsMean levels of OxPL-apoB were higher in cases than controls, but levels of OxPL-PLG and plasminogen were similar. For OxPL-apoB, individuals in the top vs bottom fifth had 2-fold higher age and sex-adjusted OR of CHD (OR = 2.61 [95%CI: 1.91, 3.55]), which were partially attenuated after adjustment for established risk factors. The findings for OxPL-apoB and CHD in PROCARDIS were comparable with those of a meta-analysis of all such studies. However, the associations of OxPL-apoB with CHD were fully attenuated by additional adjustment for Lp(a) (OR = 0.93 [0.54,1.60]). Neither OxPL-PLG nor plasminogen were associated with CHD. Overall, there were no differences in the predictive value for CHD of high vs normal levels (<20th or >80th percentile) of OxPL-apoB, OxPL-PLG, plasminogen or Lp(a) after stratifying for each other. ConclusionsThese results highlight the context-dependency of OxPL in plasma and suggest that their associated risk of CHD is chiefly mediated by their carriage on Lp(a).

Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

Prevalence of hereditary factors in different age groups in patients with acute coronary syndrome

BACKGROUND: Genetic factors are essential for the pathogenesis of coronary heart disease (CHD). This study presents the role of genetic factors in a prematurely developing disease in males under 55 years old and females under 60 years old. Additionally, genetic risk factors may also be significant for CHD development in other age groups although specific genetic factors may differ.&#x0D; AIM: The work aimed to analyze the prevalence of hereditary genetic factors in different age groups in patients with coronary heart disease.&#x0D; MATERIALS AND METHODS: The study was conducted as part of the analysis of data from two observational multicenter Russian studies of acute coronary syndrome (ACS) ORACUL I (1193 patients) and ORACUL II (1803 patients) (the study was registered on ClinicalTrials.gov with an ID number NCT04068909). The average age of patients was 63.512.45 years (1875 men and 1121 women). The study of a panel of candidate genes was performed using the polymerase chain reaction method.&#x0D; RESULTS: In order to analyze the significance of hereditary factors in patients of different ages, groups of patients with early development of CHD (men under 55 years old, women under 60 years old) were formed (n=828). The middle-aged group included men aged 5574 years and women aged 6074 years (n=1410). The older age group consisted of patients aged 75 years and older (n=602). In the group of patients with early onset coronary heart disease, the proportion of patients with aggravated heredity was higher. In the older age group, the proportion of patients with non-burdened or unknown heredity was higher. Significant differences in the frequencies of alleles and genotypes of the polymorphic variants studied by us were revealed only for the G-2667C variant of the CRP gene (the frequency of the GG genotype was 87.3% in young patients and 77.2% in the elderly and old patients (p=0.007) and for the C804A variant of the LTA gene (frequency of the CC genotype was 52 0% in young patients, 49.4% in middle-aged patients, and 34.2% in elderly and old patients, p=0.026).&#x0D; CONCLUSIONS: A burdened family history is more common among patients with early onset coronary artery disease. The differences revealed in the frequencies of genetic variants of genes encoding anti-inflammatory cytokines may indicate their role in the pathogenesis of coronary heart disease in older individuals.

Molecular screening of familial hypercholesterolemia in Icelanders

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present study, we carried out a comprehensive screening, using a next-generation sequencing (NGS) panel, for FH culprit mutations in two Icelandic studies representative of either FH families or the general population. We confirmed all previously known mutations in the FH families, and identified two subjects that had been misdiagnosed clinically at young age. We identified six new mutations in the Icelandic FH families and detected three pathogenic mutations in the general population-based study. The application of the NGS panel revealed substantial diagnostic yields in identifying pathogenic mutations, or 68.2% of those with definite clinical diagnosis of FH in the family material and 5.6-fold enrichment in the population-based genetic testing.

Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers.

Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases1-3. We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies.

LDL Oxidation and Vitamin E and Vitamin a Contents of LDL in Male Patients with Early-Onset Coronary Heart Disease and in Their 1st-Degree Male Relatives

Objective: Coronary Heart Disease CHD , of which the primary cause is atherosclerosis, is among the leading causes of mortality in the developed countries. Although many etiological agents have been considered responsible for the development of the disease, oxidized LDL low-density lipoprotein is the major risk factor. Formation of atherosclerotic lesion begins with the macrophages’ turning oxidized LDL’s into foam cells. Although many factors such as high LDL concentration, hypertension and low antioxidants in the system impair vascular structure and initiate this process, the present study is based on the genetic susceptibility and the risk groups. The present study comprised the male patients with angiography-based diagnosis of early-onset coronary heart disease, as well as their sons or 1st-degree relatives, who are considered as high-risk group. It was aimed to compare these groups in terms of susceptibility of LDL to oxidation and to measure and compare vitamin E and A contents of LDL between these groups. Homocysteine concentration, which is considered as an independent risk factor for CHD, was also compared between the groups. Materials and Methods: Susceptibility of LDL to oxidation was determined based on the formation of conjugated dienes observing for 200 minutes after being incubated with cupper cu2+ ions. Vitamin E and A contents of LDL were measured by HPLC High-performance Liquid Chromatography , which is considered as the reference method. Male patients with early-onset coronary heart disease with >50% stenosis in at least two vessels on coronary angiography and their 1st-degree relatives were compared in terms of above-mentioned three parameters. In addition, FPIA Fluorescence Polarization Immuno-Assays was used to measure homocysteine concentration. Results: Three study groups were created: Group 1 consisted of 20 patients aged 40-55 years, who had >50% stenosis in 2 and/or more vessels detected on coronary angiography; Group 2 consisted of 18 subjects aged 18-20 years, who are the 1st-degree relatives sons or brothers of Group 1; Group 3 control group consisted of healthy males aged 18-35 years. Susceptibility of LDL to oxidation showed significant difference between Group 2 and Group 3. No statistically significant difference was determined between the groups in terms of LDL content of Vitamin A and E. Homocysteine concentration was significantly higher in Group 1 and Group 2. Conclusions: Early-onset CHD can be prevented or delayed by means of relevant screening and treatment of high-risk groups in the population.

The Pattern of Risk Factor Profile and Dutch Lipid Clinic Network Criteria of Familial Hypercholesterolemia in Egyptian Patients with Premature Coronary Heart Disease

Background: Traditional risk factors (RFs), such as obesity, family history of premature coronary heart disease (CHD), hypertension, diabetes mellitus, and cigarette smoking have been shown to be significantly associated with early-onset CHD. Familial hypercholesterolemia (FH) is also a major genetic risk factor of premature CHD. Methods: This study was conducted on 100 patients with premature CHD (age<55 years in males and<60 years in females) who were admitted to hospital with acute coronary syndrome or stable coronary artery disease referred for coronary angiography, with a focus on RFs. Results: Male patients constituted 74% of the patients. In all patients, smoking (64%), obesity (64%), abdominal obesity (71%), increased LDL cholesterol (67%), hypertension (54%), positive family history of CHD (43%), and diabetes mellitus (34%) were the most prevalent risk factors. There were 26 patients diagnosed as having definite/probable FH (26%) using DLCNC score. The most common diagnosis was St-elevation myocardial infarction (STEMI) (53%) which was more prevalent in males compared to females [(60.8%) vs (30.8%), (<i>p</i><0.001)]. Female patients had higher prevalence of hypertension [(73.1%) vs (47.3%), (<i>p</i>=0.023)], diabetes mellitus [(53.8%) vs (27%), (<i>p</i>=0.013)], Obesity [(80.8%) vs (58.1%), (P=0.038)] and definite/probable FH [(46.1%) vs (18.9%), (<i>p</i>=0.024)] as compared to male patients. On the other hand, male patients had higher prevalence of smoking [(85.1%) vs (3.8%), (<i>p</i><0.001)] and reduced HDL cholesterol levels [(73%) vs (42.3%), (<i>p</i>=0.005)] compared to female patients. Conclusions: Traditional risk factors and FH were significantly related to premature CHD. Significant sex differences were also observed for multiple RFs.

A novel mutation in USF1 gene is associated with familial combined hyperlipidemia.

Familial combined hyperlipidemia or FCHL is one of the most common genetic causes of hyperlipidemia and is associated with elevation of cholesterol, triglycerides or both, and increased serum apolipoprotein B (apoB). Linkage analysis and next generation sequencing have been successfully used for identifying rare genetic variants that have moderate-to-large effects. We characterized a large pedigree from a proband identified following recruitment into the MASHAD study, in northeast Iran, with FCHL accompanied by early-onset coronary artery disease. We used linkage analysis for several candidate regions in previous studies such as 1q21-23, 11q23, and 8p, and then whole-exome sequencing to identify the disease-associated gene in this family. We identified a novel variant in the USF1 gene, leading to a substitution of a tryptophan for arginine at position 196. Arg196Trp co-segregated in all the affected family members in this pedigree with clinical syndrome and was not found in any unaffected family members of this pedigree, or in unrelated controls. We speculate that this mutation [Arg196Trp] in the USF1 gene might be associated with FCHL and early-onset coronary heart disease in this family. However, the substantial mechanism requires further investigation. These findings indicate that USF1 plays an important role in the biological pathways associated with lipid metabolism.

Soluble RAGEs and cardiovascular risk factors in adult offspring of patients with premature coronary heart disease

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls.Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls.Results: In the offspring group there were more men (p = 0.023), both groups had similar age (28.5 vs. 28.9 years; p = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s−1; p = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE (p = 0.0017), aPWV (p = 0.011) and current smoking (p = 0.0053).Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk.

A novel variant in LPL gene is associated with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common genetic disorder characterized by increased fasted serum cholesterol, triglycerides, and apolipoprotein B-100. Molecular genetic techniques such as next generation sequencing have been very successful methods for rare variants finding with a moderate-to large effect. In this study, we characterized a large pedigree from MASHAD study in northeast Iran with coinheritance of FCHL and early-onset coronary heart disease. In this family, we used whole-exome sequencing and Sanger sequencing to determine the disease-associated gene. We identified a novel variant in the LPL gene, leading to a substitution of an asparagine for aspartic acid at position 151. The D151N substitution cosegregated with these characters in all affected family members in the pedigree but it was absent in all unaffected members in this family. We speculated that the mutation D151N in LPL gene might be associated with FCHL and early-onset coronary heart disease in this family. However, the substantial mechanism requires further investigation.

Rare Protein-Truncating Variants in APOB, Lower Low-Density Lipoprotein Cholesterol, and Protection Against Coronary Heart Disease.

Background Familial hypobetalipoproteinemia is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding APOB (apolipoprotein B), the major protein component of LDL (low-density lipoprotein) and triglyceride-rich lipoprotein particles. Whether heterozygous APOB deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in APOB with circulating LDL-C (LDL cholesterol), triglycerides, and risk for CHD. Methods We sequenced the APOB gene in 29 Japanese hypobetalipoproteinemia families, as well as 57 973 individuals derived from 12 CHD case-control studies-18 442 with early-onset CHD and 39 531 controls. We defined PTVs as variants that lead to a premature stop, disrupt canonical splice-sites, or lead to insertions/deletions that shift reading frame. We tested the association of rare APOB PTV carrier status with blood lipid levels and CHD. Results Among 29 familial hypobetalipoproteinemia families, 8 families harbored APOB PTVs. Carrying 1 APOB PTV was associated with 55 mg/dL lower LDL-C ( P=3×10-5) and 53% lower triglyceride level ( P=2×10-4). Among 12 case-control studies, an APOB PTV was present in 0.038% of CHD cases as compared to 0.092% of controls. APOB PTV carrier status was associated with a 43 mg/dL lower LDL-C ( P=2×10-7), a 30% decrease in triglycerides ( P=5×10-4), and a 72% lower risk for CHD (odds ratio, 0.28; 95% CI, 0.12-0.64; P=0.002). Conclusions Rare PTV mutations in APOB which are associated with lower LDL-C and reduced triglycerides also confer protection against CHD.

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.

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.

Lipoprotein abnormalities in South Asians and its association with cardiovascular disease: Current state and future directions.

South Asians have a high prevalence of coronary heart disease (CHD) and suffer from early-onset CHD compared to other ethnic groups. Conventional risk factors may not fully explain this increased CHD risk in this population. Indeed, South Asians have a unique lipid profile which may predispose them to premature CHD. Dyslipidemia in this patient population seems to be an important contributor to the high incidence of coronary atherosclerosis. The dyslipidemia in South Asians is characterized by elevated levels of triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, elevated lipoprotein(a) levels, and a higher atherogenic particle burden despite comparable low-density lipoprotein cholesterol levels compared with other ethnic subgroups. HDL particles also appear to be smaller, dysfunctional, and proatherogenic in South Asians. Despite the rapid expansion of the current literature with better understanding of the specific lipid abnormalities in this patient population, studies with adequate sample sizes are needed to assess the significance and contribution of a given lipid parameter on overall cardiovascular risk in this population. Specific management goals and treatment thresholds do not exist for South Asians because of paucity of data. Current treatment recommendations are mostly extrapolated from Western guidelines. Lastly, large, prospective studies with outcomes data are needed to assess cardiovascular benefit associated with various lipid-lowering therapies (including combination therapy) in this patient population.

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

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

Patients’ Perceptions and Experiences of Familial Hypercholesterolemia, Cascade Genetic Screening and Treatment

Familial hypercholesterolemia (FH) is a serious genetic disorder affecting approximately 1 in every 300 to 500 individuals and is characterised by excessively high low-density lipoprotein (LDL) cholesterol levels, substantially increased risk of early-onset coronary heart disease (CHD) and premature mortality. If FH is untreated, it leads to a greater than 50 % risk of CHD in men by the age of 50 and at least 30 % in women by the age of 60. FH can be diagnosed through genetic screening and effectively managed through pharmacological treatment and lifestyle changes. Familial hypercholesterolemia (FH) is a genetic health condition that increases the risk of cardiovascular disease. Although FH can be effectively managed with appropriate pharmacological and dietary interventions, FH detection rate through genetic screening remains low. The present study explored perceptions and experiences of FH patients (N = 18) involved in a genetic cascade screening programme. Face-to-face interviews were conducted to assess patients' knowledge and understanding of FH, explore factors linked to adherence to health-protective behaviours and examine perceptions of genetic screening. Thematic analysis of interviews revealed four themes: disease knowledge, severity of FH, lifestyle behavioural change and barriers to cascade screening and treatment. Participants recognised FH as a permanent, genetic condition that increased their risk of CHD and premature mortality. Many participants dismissed the seriousness of FH and the importance of lifestyle changes because they perceived it to be effectively managed through medication. Despite positive attitudes toward screening, many participants reported that relatives were reluctant to attend screening due to their relatives' 'fatalistic' outlook or low motivation. Participants believed that they had insufficient authority or control to persuade family members to attend screening and welcomed greater hospital assistance for contact with relatives. Findings support the adoption of direct methods of recruitment to cascade screening led by medical professionals, who were perceived as having greater authority. Other implications included the need for clinicians to provide clear information, particularly to those who are asymptomatic, related to the seriousness of FH and the necessity for adherence to medication and lifestyle changes.

Urban-Rural Differences in Coronary Heart Disease Mortality in the United States: 1999–2009

Coronary heart disease (CHD) mortality has declined in the past few decades; however, it is unclear whether the reduction in CHD deaths has been similar across urbanization levels and in specific racial groups. We describe the pattern and magnitude of urban-rural variations in CHD mortality in the U.S. Using data from the National Center for Health Statistics, we examined trends in death rates from CHD from 1999 to 2009 among people aged 35-84 years, in each geographic region (Northeast, Midwest, West, and South) and in specific racial-urbanization groups, including black and white people in large and medium metropolitan (urban) areas and in non-metropolitan (rural) areas. We also examined deaths from early-onset CHD in females aged <65 years and males aged <55 years. From 1999 to 2009, there was a 40% decline in age-adjusted CHD mortality. The trend was similar in black and white people but was more pronounced in urban than in rural areas, resulting in a crossover in 2007, when rural areas began showing a higher CHD mortality than urban areas. White people in large metropolitan areas had the largest decline (43%). Throughout the study period, CHD mortality remained higher in black people than in white people, and, in the South, it remained higher in rural than in urban areas. For early-onset CHD, the mortality decline was more modest (30%), but overall trends by urbanization and region were similar. Favorable national trends in CHD mortality conceal persisting disparities for some regions and population subgroups (e.g., rural areas and black people).