Risk Of Premature Cardiovascular Disease Research Articles

Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

Achilles tendon ultrasonography in the clinical screening of familial hypercholesterolaemia - a cross-sectional analysis.

People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS). The aim of the study was to determine whether ultrasound detects more Achilles tendon xanthomas (ATX) than clinical examination. We recruited 100 consecutive patients with LDL-C ≥4 mmol/l. Achilles tendons were evaluated through clinical examination by trained physicians and sonographic examination by another physician blind to the results of clinical examination. Blind second readings of ultrasound images were performed by an expert in musculoskeletal ultrasound. We compared the proportion of patients with ATX detected by either clinical examination or ultrasound and the proportion of patients with a probable/definite familial hypercholesterolaemia diagnosis on the DLCNS before and after ultrasound. Mean (SD) age was 47 (12) years; mean highest LDL-C was 6.57 mmol/l (2.2). ATX were detected in 23% of patients by clinical examination and in 60% by ultrasound. In consequence, 43% had a probable/definite diagnosis of familial hypercholesterolaemia on the DLCNS using clinical examination compared with 72% when ultrasound was used. Compared to clinical examination, ultrasound examination of the Achilles tendon substantially improves the detection of ATX and may help to better identify patients with familial hypercholesterolaemia who are at high risk for premature cardiovascular disease.

Microarray analysis identifies human apoA-IMilano and apoA-II as determinants of the liver gene expression related to lipid and energy metabolism

The phenotype of individuals carrying the apolipoprotein A-IMilano (apoA-IM), the mutant form of human apoA-I (apoA-I), is characterized by very low concentrations of HDL and apoA-I, and hypertriglyceridemia. Paradoxically, these subjects are not found to be at increased risk of premature cardiovascular disease compared to controls. Besides, various in vitro and in vivo studies have demonstrated that apoA-IM possesses greater anti-atherosclerotic activity compared to apoA-I. The molecular mechanisms explaining the apoA-IM carrier's phenotype and the apoA-IM higher efficacy are still not fully elucidated. To investigate such mechanisms, we crossed previously generated apoA-I (A-I k-in) or apoA-IM knock-in mice (A-IM k-in) with transgenic mice expressing human apoA-II but lacking murine apoA-I (hA-II) to generate hA-II/A-I k-in, and hA-II/A-IM k-in, respectively. These genetically modified mice completely reproduced the apoA-IM carrier's phenotype, including hypoalphalipoproteinemia and hypertriglyceridemia. Furthermore, by using the microarray methodology, we investigated the intrinsic differences in hepatic gene expression among these k-in mouse lines. The expression of 871, 1,018, 1129 and 764 genes was significantly altered between 1) hA-II/A-I and hA-II/A-IM k-in; 2) A-IM and hA-II/A-IM k-in; 3) A-I and A-IM; 4) A-I and hA-II/A-I k-in liver samples, respectively. Bioinformatics analysis highlighted that the hepatic expression of two genes, Elovl6 and Gatm, related to fatty acid/lipid and energy metabolism, respectively, is influenced by the presence of the apoA-IM natural variant and/or apoA-II.

An integration-free iPSC line ZZUNEUi029-A derived from peripheral blood mononuclear cells of a patient with familial hypercholesterolemia carrying a mutation in LDLR gene

Familial hypercholesterolemia is a hereditary disorder that causes severely elevated low-density lipoprotein levels, which can lead to an increased risk for premature cardiovascular disease. Mutations in the LDLR gene are the most common cause of familial hypercholesterolemia. In this study, we report the generation of ZZUNEUi029-A, a human induced pluripotent stem cell line (hiPSC) from a male patient with c. 622 G → A in LDLR gene using non-integrative Sendai viral reprogramming technology. This cell line expressed pluripotency markers, had a normal male karyotype (46XY) and maintained the ability to differentiate into the three germ layers in vitro.

Novel Tools for Comprehensive Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants.

Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused mainly by substitutions in the low-density lipoprotein receptor (LDLR) gene, leading to an increased risk of premature cardiovascular diseases. Tremendous advances in sequencing techniques have resulted in the discovery of more than 3000 variants of the LDLR gene, but not all of them are clinically relevant. Therefore, functional studies of selected variants are needed for their proper classification. Here, a single-cell, kinetic, fluorescent LDL uptake assay was applied for the functional analysis of LDLR variants in a model of an LDLR-deficient human cell line. An LDLR-defective HEK293T cell line was established via a CRISPR/Cas9-mediated luciferase-puromycin knock-in. The expressing vector with the LDLR gene under the control of the regulated promoter and with a reporter gene has been designed to overproduce LDLR variants in the host cell. Moreover, an LDLR promoter-luciferase knock-in reporter system has been created in the human cell line to study transcriptional regulation of the LDLR gene, which can serve as a simple tool for screening and testing new HMG CoA reductase-inhibiting drugs for atherosclerosis therapy. The data presented here demonstrate that the obtained LDLR-deficient human cell line HEK293T-ldlrG1 and the dedicated pTetRedLDLRwt expression vector are valuable tools for studying LDL internalization and functional analysis of LDLR and its genetic variants. Using appropriate equipment, LDL uptake to a single cell can be measured in real time. Moreover, the luciferase gene knock-in downstream of the LDLR promotor allows the study of promoter regulation in response to diverse conditions or drugs. An analysis of four known LDLR variants previously classified as pathogenic and benign was performed to validate the LDLR-expressing system described herein with the dedicated LDLR-deficient human cell line, HEK293T-ldlrG1.

Determinants of lipid-lowering medication prescribing in a multi-ethnic adult population diagnosed with familial hypercholesterolaemia in South London.

Familial hypercholesterolaemia (FH) (prevalence 1 in 250) is an inherited condition that significantly increases risk of premature cardiovascular disease. Early diagnosis can potentially normalise cardiovascular risk with lipid-lowering medicines (statins and fibrates). Only 7% of patients with FH are identified in the UK. Improving identification, and understanding disparities in ascertainment and management, is an NHS priority. To assess determinants of lipid-lowering prescribing in ethnically diverse adults with an FH code. METHOD: Retrospective cross-sectional analysis of Lambeth DataNet, containing anonymised adult patient data from 41 practices in South London. Stata 17 was used to run sequential multilevel logistic regression models, adjusted for practice effects, to estimate the odds of no lipid-lowering prescription in FH-coded adults; this was assessed across 10 ethnic groups and other patient-level factors: demographic, socioeconomic, lifestyle, comorbidities, and practice factors (consultation frequency and practice list size). One hundred and sixty-one of 801 (20%) of adults with an FH code received no lipid-lowering medication. The fully adjusted model for no lipid-lowering prescriptions showed the following associations: age (years) odds ratio (OR) 0.93 (P<0.001, 95% confidence interval [CI] = 0.91 to 0.95), male sex OR 0.47 (P = 0.002, 95% CI = 0.29 to 0.76), diabetes OR 0.26 (P = 0.04, 95% CI = 0.70 to 0.96), hypertension OR 0.30 (P<0.01, 95% CI = 0.12 to 0.72), and frequency of GP attendance OR 0.48 (P = 0.03, 95% CI = 0.24 to 0.94). Sensitivity analyses examining determinants of high-intensity statin prescribing found similar results. The study suggests important determinants of lipid-lowering prescribing in an ethnically diverse adult population included older age, male sex, hypertension, and diabetes. Ethnicity showed no significant associations with lipid-lowering prescribing after adjusting for other determinants including deprivation measures.

The association between adolescent depression and dyslipidemia

BackgroundChildren and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest evidence of dyslipidemia, a key risk factor for CVD, is unknown. MethodsYouth recruited through an ambulatory psychiatry clinic and the community, were categorized following diagnostic interview as MDD or as healthy controls [HC]. CVD risk factors including high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride concentrations were collected. Depression severity was measured using the Center for Epidemiological Studies Depression Scale for Children. The associations of diagnostic group as well as depressive symptom severity with lipid concentrations were examined using multiple regression analyses. Models were adjusted for age, sex, and standardized Body Mass Index. ResultsParticipants (n = 243) were 68 % female with a mean age of 15.04 ± 1.81 years. MDD and HC participants had comparable levels of dyslipidemia (MDD: 48 %, HC: 46 %, p > .7) and hypertriglyceridemia (MDD: 34 %, HC: 30 %, p > .7). Among depressed adolescents, greater depressive symptoms were associated with higher total cholesterol concentrations in unadjusted models only. Greater depressive symptoms were associated with higher HDL concentrations and a lower triglyceride-to-HDL ratio, after adjusting for covariates. LimitationsCross-sectional design. ConclusionsAdolescents with clinically significant depressive symptoms manifested similar levels of dyslipidemia as healthy youth. Future studies examining the prospective trajectories of depressive symptoms and lipid concentrations are needed to determine the point at which dyslipidemia emerges in the course of MDD, and the mechanism of the association that imparts increased CVD risk for depressed youth.

Association Between Chronic Hypertension and the Risk of 12 Cardiovascular Diseases Among Parous Women: The Role of Adverse Pregnancy Outcomes.

Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03-2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96-15.6) for heart failure to 2.66 (2.17-3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47-7.94) for subarachnoid hemorrhage to 1.26 (0.59-2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48-4.31) for intracerebral hemorrhage to 1.33 (1.26-1.41) for stable angina. We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Association of Multitrajectories of Lipid Indices With Premature Cardiovascular Disease: A Cohort Study.

Background The multitrajectory model can identify joint longitudinal patterns of different lipids simultaneously, which might help better understand the heterogeneous risk of premature cardiovascular disease (CVD) and facilitate targeted prevention programs. This study aimed to investigate the associations between multitrajectories of lipids with premature CVD. Methods and Results The study enrolled 78 526 participants from the Kailuan study, a prospective cohort study in Tangshan, China. Five distinct multitrajectories of triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol over 6-year exposure were identified on the basis of Nagin's criteria, using group-based multitrajectory modeling. During a median follow-up of 6.75 years (507 645.94 person-years), 665 (0.85%) premature CVDs occurred. After adjustment for confounders, the highest risk of premature CVD was observed in group 4 (the highest and increasing triglyceride, optimal and decreasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (hazard ratio [HR], 2.13 [95% CI, 1.36-3.32]), followed by group 5 (high and decreasing triglyceride, optimal and increasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (HR, 2.07 [95% CI, 1.45-2.98]), and group 3 (optimal and increasing triglyceride, borderline high and increasing LDL-C, optimal and decreasing high-density lipoprotein cholesterol) (HR, 1.90 [95% CI, 1.32-2.73]). Conclusions Our results showed that the residual risk of premature CVD caused by increasing triglyceride levels remained high despite the fact that LDL-C levels were optimal or declining over time. These findings emphasized the importance of assessing the joint longitudinal patterns of lipids and undertaking potential interventions on triglyceride lowering to reduce the residual risk of premature CVD, even among individuals with optimal LDL-C levels.

How Genetic Variants in Children with Familial Hypercholesterolemia Not Only Guide Detection, but Also Treatment

Familial hypercholesterolemia (FH) is a hereditary disorder that causes severely elevated low-density lipoprotein (LDL-C) levels, which leads to an increased risk for premature cardiovascular disease. A variety of genetic variants can cause FH, namely variants in the genes for the LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and/or LDL-receptor adaptor protein 1 (LDLRAP1). Variants can exist in a heterozygous form (HeFH) or the more severe homozygous form (HoFH). If affected individuals are diagnosed early (through screening), they benefit tremendously from early initiation of lipid-lowering therapy, such as statins, and cardiovascular imaging to detect possible atherosclerosis. Over the last years, due to intensive research on the genetic basis of LDL-C metabolism, novel, promising therapies have been developed to reduce LDL-C levels and subsequently reduce cardiovascular risk. Results from studies on therapies focused on inhibiting PCSK9, a protein responsible for degradation of the LDLR, are impressive. As the effect of PCSK9 inhibitors (PCSK9-i) is dependent of residual LDLR activity, this medication is less potent in patients without functional LDLR (e.g., null/null variant). Novel therapies that are expected to become available in the near future focused on inhibition of another major regulatory protein in lipid metabolism (angiopoietin-like 3 (ANGPTL3)) might dramatically reduce the frequency of apheresis in children with HoFH, independently of their residual LDLR. At present, another independent risk factor for premature cardiovascular disease, elevated levels of lipoprotein(a) (Lp(a)), cannot be effectively treated with medication. Further understanding of the genetic basis of Lp(a) metabolism, however, offers a possibility for the development of novel therapies.

Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up

Background and aimsThe concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. MethodsData was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. ResultsSubjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. ConclusionOur study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

Differential affinity chromatography reveals a link between Porphyromonas gingivalis-induced changes in vascular smooth muscle cell differentiation and the type 9 secretion system.

Porphyromonas gingivalis is implicated in adverse pregnancy outcome. We previously demonstrated that intrauterine infection with various strains of P. gingivalis impairs the physiologic remodeling of the uterine spiral arteries (IRSA) during pregnancy, which underlies the major obstetrical syndromes. Women diagnosed with IRSA also have a greater risk for premature cardiovascular disease in later life. The dysregulated plasticity of vascular smooth muscle cells (VSMCs) is present in both IRSA and premature cardiovascular events. We hypothesized that VSMCs could serve as a bait to identify P. gingivalis proteins associated with dysregulated VSMC plasticity as seen in IRSA. We first confirmed that dams with P. gingivalis A7UF-induced IRSA also show perturbed aortic smooth muscle cell (AoSMC) plasticity along with the P. gingivalis colonization of the tissue. The in vitro infection of AoSMCs with IRSA-inducing strain A7UF also perturbed AoSMC plasticity that did not occur with infection by non-IRSA-inducing strain W83. Far-Western blotting with strain W83 and strain A7UF showed a differential binding pattern to the rat aorta and primary rat AoSMCs. The affinity chromatography/pull-down assay combined with mass spectrometry was used to identify P. gingivalis/AoSMC protein interactions specific to IRSA. Membrane proteins with a high binding affinity to AoSMCs were identified in the A7UF pull-down but not in the W83 pull-down, most of which were the outer membrane components of the Type 9 secretion system (T9SS) and T9SS cargo proteins. Additional T9SS cargo proteins were detected in greater abundance in the A7UF pull-down eluate compared to W83. None of the proteins enriched in the W83 eluate were T9SS components nor T9SS cargo proteins despite their presence in the prey preparations used in the pull-down assay. In summary, differential affinity chromatography established that the components of IRSA-inducing P. gingivalis T9SS as well as its cargo directly interact with AoSMCs, which may play a role in the infection-induced dysregulation of VSMC plasticity. The possibility that the T9SS is involved in the microbial manipulation of host cell events important for cell differentiation and tissue remodeling would constitute a new virulence function for this system.

Clinical response to lifestyle counseling for dyslipidemia and elevated blood pressure in childhood cancer survivors.

Childhood cancer survivors (CCS) have increased risk of premature cardiovascular disease. Whether they respond similarly to lifestyle changes for elevated blood pressure (BP), body mass index (BMI), and dyslipidemia to those without history of childhood cancer is unknown. This retrospective cohort study included CCS and 3:1 age- and sex-matched controls treated at Boston Children's Hospital Preventive Cardiology (2010-2019) using lifestyle management based on National Heart, Lung, and Blood Institute (NHLBI) guidelines. Change in BMI, BP, and lipids were analyzed. We included 52 CCS and 162 controls with a median age of approximately 16years. More CCS (84.3%) had elevated baseline fasting triglycerides (TG) than controls (49.4%) (p < .001). More CCS (62.5%) also had abnormal baseline high-density lipoprotein cholesterol (HDL-C) compared to controls (35.2%) (p = .001). Baseline BMI, BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were similar between groups. Over 15weeks [IQR: 10.5-26], CCS had greater decrease in TG than controls (72.5 vs. 17mg/dl decrease, p = .095). BP improved in 5% of CCS versus 38% of controls (p = .008). For both, BMI, TC, LDL-C, and HDL-C remained stable. CCS with stem cell transplantation (SCT) had a TC increase of 5% (6mg/dl) compared to a decrease of 9% (19mg/dl) among CCS without SCT (p = .02). CCS demonstrated similar improvement in lipids, but impaired BP lowering in response to lifestyle management compared to controls. Further prospective studies are needed to determine if earlier pharmaceutical treatment is warranted in this higher risk population and for the long-term risk reductions of these approaches.

Impact of cognitive ability in young adult age on risk of cardiovascular disease and presence of subclinical carotid plaques among men aged 60 years

Abstract Background A clear association between low cognitive ability in early adult life and increased risk of premature cardiovascular diseases (CVD) has been demonstrated [1]. However, the mechanisms for this relationship are not fully understood. Also, despite the evidence on low early cognitive ability being a risk factor for CVD, specific CVD prevention studies in this group has not been reported and low cognitive ability has not been mentioned in clinical guidelines for prevention of CVD. Purpose To clarify the interrelationships between early adult life cognitive ability and late middle-life health behaviors and the risk of CVD and presence of subclinical carotid plaque. Methods Register-data from psychological testing of men at age 18–19 years in the Swedish Enlistment Battery was used (n=1009), and early cognitive ability was calculated as the mean of four subtests on a scale from 1 to 9 (logical-inductive ability, verbal ability, visuospatial ability and technical understanding). A lifestyle index on a scale from 4 to 12, which was calculated as the sum of self-reported diet, physical activity, smoking and alcohol consumption, where each behavior was divided into 3 levels and the most health-promoting level was the highest level, as well as clinical CVD risk factors were collected at age 60 years within the VIPVIZA RCT (Västerbotten Intervention Program – Visualization of subclinical Atherosclerotic disease for optimum cardiovascular prevention) [2]. Risk of CVD was calculated as SCORE and presence of carotid plaques was identified, based on ultrasonography and defined according to Mannheim consensus [2]. Early cognitive ability's association to SCORE and presence of carotid plaques was assessed using linear and logistic regression, respectively. The linear regression was performed using restricted cubic splines to account for non-linearity. Results Early cognitive ability and the lifestyle index were normally distributed (mean 4.24, SD 1.12 and mean 9.95, SD 1.484, respectively). Mean of SCORE was 2.6%, SD 1.4. Carotid plaques were observed among 61%. A statistically significant negative association between early cognitive ability and SCORE was found (p=0.009, Figure 1). Higher early cognitive ability was also associated with a decreased risk for carotid plaques, with an odds ratio 0.86 for each increase of one point in cognitive ability (95% CI: 0.76–0.96, p=0.007). Conclusion Among men, higher cognitive ability at age 18–19 years is associated with lower risk of CVD and lower risk of having carotid plaque at age 60 years Additional modelling analyses are warranted to clarify the mediating and moderating roles of socioeconomic position, lifestyle and clinical CVD risk factors on the path between early cognitive ability and risk of CVD and subclinical atherosclerosis. This may guide development of tailored interventions to reduce the inequity in CVD due to cognitive ability. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swedish Research CouncilRegion Västerbotten

CARDIOMETABOLIC RISK IN INDIVIDUALS WITH BIPOLAR DISORDER AND THEIR OFFSPRING

Bipolar disorder (BD) is a highly heritable illness that is associated with increased risk of premature cardiovascular disease (CVD). Prior studies have observed increased CVD risk factors in unaffected adult relatives of adults with BD. Here we examined metabolic syndrome (MetS) and its components in a controlled study of adults with BD and their offspring.

Features of the metabolic syndrome and subclinical atherosclerosis in patients with cerebrotendinous xanthomatosis: An augmented risk for premature cardiovascular disease.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disease, caused by deficiency of sterol-27-hydroxylase. Xanthomatous lesions in numerous tissues, and an elevation of cholestanol levels, characterize the disease. Its natural course is progressive neurologic deterioration, leading to premature death. Chronic treatment with oral chenodeoxycholic acid (CDCA) reduces cholestanol levels. Occurrence of premature atherosclerosis has been described in CTX in an unknown mechanism. Aim: The aim of the current work was to evaluate the potential metabolic abnormalities and preclinical vascular changes in Israeli CTX patients. Methods: Ten subjects with CTX were studied. Features of the metabolic syndrome were evaluated, and carotid intima media thickness (cIMT) was measured in the common carotid arteries. Results: All patients were diagnosed with CTX, and all received treatment with CDCA, which resulted in normalization of their plasma cholestanol levels. At the conclusion of the follow up, risk factors for CVD and features of MS were present in all the patients and in three patients, cIMT was higher compared to control subjects. Conclusion: Cardiovascular risk factors and premature vascular changes exist in young CTX patients and proper assessment should be implemented with preventive measures to reduce the risk of atherosclerotic cardiovascular disease in CTX patients.

Current causes of death in familial hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH).MethodsA case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members.ResultsA total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73–4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk.ConclusionsCVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality.

Features of the metabolic syndrome and subclinical atherosclerosis in patients with cerebrotendinous xanthomatosis: An augmented risk for premature cardiovascular disease

Background and Aims : Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disease caused by mutations of the CYP27A1 gene, resulting in deficiency of sterol-27-hydroxylase, a key enzyme involved in hepatic bile acid synthesis from cholesterol. Xanthomatous lesions in numerous tissues, in conjunction with an elevation of plasma and tissue cholestanol levels. The natural course of CTX is progressive neurologic deterioration from childhood through adulthood, leading to diffuse damage of the central and peripheral nervous systems and eventually to premature death.

Current causes of death in familial hypercholesterolemia

Background and Aims : Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined and effective lipid-lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heFH.