Traditional Risk Factors For Atherosclerosis Research Articles

Plasma osteopontin versus intima media thickness of the common carotid arteries in well-characterised patients with systemic lupus erythematosus.

ObjectiveThe progress of accelerated atherosclerosis in systemic lupus erythematosus (SLE) is incompletely understood. Circulating osteopontin (OPN) is increased in autoimmune conditions, e.g. SLE, and its serum concentration was recently reported to associate with subclinical atherosclerosis in SLE, as measured by carotid intima-media thickness. The aim of this study was to investigate whether OPN may be used as a surrogate biomarker of subclinical atherosclerosis in SLE patients with different disease phenotypes.MethodsWe recruited 60 well-characterised SLE cases and 60 age- and sex-matched healthy controls. The SLE cases were divided into three different disease phenotypes: SLE with antiphospholipid syndrome (APS), lupus nephritis, and isolated skin and joint involvement. Plasma OPN was detected by ELISA (Quantikine®, R&D Systems). Common carotid arteries intima media thickness was compared between the studied groups in relation to OPN levels and risk factors for vascular changes. Intima media thickness of common carotid arteries was measured by using a sensitive ultrasound technique (LOGIQ™ E9 ultrasound, GE Healthcare).ResultsOPN levels were significantly higher among the entire SLE group (n = 60) compared to the healthy controls (P = 0.03). SLE cases with concomitant APS (n = 20) showed higher OPN levels than the controls (P = 0.004), whereas none of the other two subgroups differed significantly from the healthy controls. OPN and intima media thickness were correlated to several traditional risk factors of atherosclerosis, as well as to SLE-related factors. Yet, no significant correlation was observed between OPN levels and ultrasound findings of the common carotid arteries.ConclusionsIn line with previous studies, we observed increased OPN levels among SLE patients as compared to matched controls. However, the OPN concentrations did not correlate with intima media thickness of the common carotid arteries. Based on our findings, the use of OPN as a surrogate biomarker of subclinical atherosclerosis in SLE subjects, regardless of clinical phenotypes, cannot be recommended.

Genetic and epigenetic factors regulating the expression and function of the vitamin D receptor in patients with coronary artery disease

Coronary artery disease (CAD) remains the leading cause of death and disability in developed countries. Using traditional risk factors for CAD, it is possible to predict the likelihood of acute coronary events in no more than 50% of cases. Therefore, the study of influence of genetic and epigenetic factors on the development of CAD is extremely important. Research in recent years has shown that vitamin D deficiency is a new risk factor for atherosclerosis and immune inflammation. Vitamin D implements protective effects against immune inflammation through receptors in the vascular wall. A single nucleotide polymorphism of the vitamin D receptor (VDR) gene is a potential risk factor for CAD associated with low vitamin D levels. VDR expression correlates with the expression of pro-inflammatory cytokines and is regulated by microRNAs — microRNA-125a-5p, microRNA-125b-5p, microRNA-214-3p and microRNA-21 These microRNAs regulate the action, synthesis and metabolism of vitamin D and can themselves be influenced by VDR signals through dynamic feedback, which can lead to destabilization of mRNA and inhibition of translation. This literature review highlights the effect of a single nucleotide polymorphism of the VDR gene and microRNA on the pathogenetic mechanisms of CAD.

Sortilin as a Biomarker for Cardiovascular Disease Revisited.

Genetic variants in the genomic region containing SORT1 (encoding the protein sortilin) are strongly associated with cholesterol levels and the risk of coronary artery disease (CAD). Circulating sortilin has therefore been proposed as a potential biomarker for cardiovascular disease. Multiple studies have reported association between plasma sortilin levels and cardiovascular outcomes. However, the findings are not consistent across studies, and most studies have small sample sizes. The aim of this study was to evaluate sortilin as a biomarker for CAD in a well-characterized cohort with symptoms suggestive of CAD. In total, we enrolled 1,173 patients with suspected stable CAD referred to coronary computed tomography angiography. Sortilin was measured in plasma using two different technologies for quantifying circulating sortilin: a custom-made enzyme-linked immunosorbent assay (ELISA) and OLINK Cardiovascular Panel II. We found a relative poor correlation between the two methods (correlation coefficient = 0.21). In addition, genotyping and whole-genome sequencing were performed on all patients. By whole-genome regression analysis of sortilin levels measured with ELISA and OLINK, two independent cis protein quantitative trait loci (pQTL) on chromosome 1p13.3 were identified, with one of them being a well-established risk locus for CAD. Incorporating rare genetic variants from whole-genome sequence data did not identify any additional pQTLs for plasma sortilin. None of the traditional CAD risk factors, such as sex, age, smoking, and statin use, were associated with plasma sortilin levels. Furthermore, there was no association between circulating sortilin levels and coronary artery calcium score (CACS) or disease severity. Sortilin did not improve discrimination of obstructive CAD, when added to a clinical pretest probability (PTP) model for CAD. Overall, our results indicate that studies using different methodologies for measuring circulating sortilin should be compared with caution. In conclusion, the well-known SORT1 risk locus for CAD is linked to lower sortilin levels in circulation, measured with ELISA; however, the effect sizes are too small for sortilin to be a useful biomarker for CAD in a clinical setting of low- to intermediate-risk chest-pain patients.

Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT.MethodsCross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression.ResultsTwenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables.ConclusionSubclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

Association of \u201chypertriglyceridemic waist\u201d with increased 5-year risk of subclinical atherosclerosis in a multi-ethnic population: a prospective cohort study

BackgroundHypertriglyceridemic waist (HTGW), which incorporates measures of waist circumference and levels of triglyceride in blood, could act as an early-stage predictor to identify the individuals at high-risk for subclinical atherosclerosis. Previous studies have explored the cross-sectional association between HTGW and atherosclerosis; however, understanding how this association might change over time is necessary. This study will assess the association between HTGW with 5-year subclinical carotid atherosclerosis.Methods517 participants of Aboriginal, Chinese, European, and South Asian ethnicities were examined for baseline HTGW and 5-year indices of subclinical atherosclerosis (intima media thickness (mm), total area (mm2), and plaque presence). Family history of cardiovascular disease, sociodemographic measures (age, sex, ethnicity, income level, maximum education), and traditional risk factors (systolic blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, body mass index) were incorporated into the models of association. These models used multiple linear regression and logistic regression.ResultsBaseline HTGW phenotype is a statistically significant and clinically meaningful predictor of 5-year intima media thickness (β = 0.08 [0.04, 0.11], p < 0.001), total area (β = 0.20 [0.07, 0.33], p = 0.002), and plaque presence (OR = 2.17 [1.13, 4.19], p = 0.02) compared to the non-HTGW group independent of sociodemographic factors and family history. However, this association is no longer significant after adjusting for the traditional risk factors of atherosclerosis (p = 0.27, p = 0.45, p = 0.66, respectively). Moreover, change in status of HTGW phenotype does not correlate with change in indices of atherosclerosis over 5 years.ConclusionsOur results suggest that when the traditional risk factors of atherosclerosis are known, HTGW may not offer additional value as a predictor of subclinical atherosclerosis progression over 5 years.

Carotid Intima-Media Thickness and Cardiovascular Risk Factors

Albers SS et al. reviewed carotid artery variation in the development of atherosclerotic carotid artery disease (Int J Med Students. 2019 Sep-Dec;7(3):82-91) commenting on changes from birth to older ages that can contribute to disorders of intramural elastin even in absence of disease. Considering the coexistence of traditional risk factors of atherosclerosis, additional comments are posed about measurements of carotid intima-media thickness in patients with obesity, chronic renal failure, and secondary hyperparathyroidism. The authors emphasized the need for further research to validate preventive procedures initiating since prenatal.

Genetic risk score associations for myocardial infarction are comparable in persons with and without rheumatoid arthritis: the population-based HUNT study

Persons with rheumatoid arthritis (RA) have increased risk of myocardial infarction (MI). Overlapping associations with MI of weighted genetic risk scores (wGRS) for coronary artery disease (CAD) and RA is unknown in a population-based setting. Data from the prospective Nord-Trøndelag Health Study (HUNT2: 1995–1997 and HUNT3: 2006–2008) were used. wGRS added each participant’s carriage of all risk variants weighted by the coefficient from published association studies. Published wGRS for CAD and RA were analysed in Cox regression with MI as outcome, age as analysis time, and censoring at the first MI, death, or 31.12.2017. 2609 of 61,465 participants developed MI during follow-up (mean 17.7 years). The best-fitting wGRS for CAD and RA included 157 and 27 single-nucleotide polymorphisms, respectively. In multivariable analysis including traditional CAD risk factors, the CAD wGRS was associated with MI [hazard ratio = 1.23 (95% CI 1.18–1.27) for each SD increase, p < 0.0001] in RA patients (n = 433) and controls. The RA wGRS was not significant (p = 0.06). Independently from traditional risk factors, a CAD wGRS was significantly associated with the risk for MI in RA patients and controls, whereas an RA wGRS was not. The captured genetic risk for RA contributed little to the risk of MI.

Association Between Pulse Pressure and Carotid Intima-Media Thickness Among Low-Income Adults Aged 45 Years and Older: A Population-Based Cross-Sectional Study in Rural China.

Worldwide, the stroke burden remains severe, especially for people in low socioeconomic groups. Atherosclerosis is a leading cause of stroke that is attracting increasingly greater attention. Blood pressure, including pulse pressure (PP) and systolic (SBP) and diastolic (DBP) blood pressures, is a traditional risk factor for atherosclerosis; its association with carotid intima-media thickness (CIMT) has also been widely studied. However, published studies have not reported on the relationship between PP and CIMT in low-income adults. Thus, this study investigated the relationship between PP and CIMT in a low-income population, in China. A total of 3,789 people, aged ≥45 years and without histories of stroke or cardiovascular disease, were recruited into this study. B-mode ultrasonography was performed to determine CIMTs. Demographic characteristics, physical examination data, previous medical histories, and laboratory test results were collected for each study participant. Multiple linear regression models were used to analyze the association between CIMT and PP. The mean CIMT was 567.1 μm (males, 583.5 μm; females, 555.7 μm). The SBP, DBP, PP, and mean arterial pressure (MAP) values were all positively correlated with CIMT, in the univariate analysis; PP and MAP showed the strongest correlations. In addition, in three multiple linear regression models, PP was shown to be significantly associated with CIMT; each 1-mm Hg increase in PP resulted in a CIMT increase of ≥0.41 μm (all P < 0.001). Our results demonstrated that, when compared with SBP, DBP, and MAP, PP may be the best predictor of CIMT. Thus, controlling blood pressure, especially PP levels, is vital to decreasing the prevalence of atherosclerosis, especially in this low socioeconomic status population in China.

Association between uric acid and atherosclerosis in community-dwelling older people: The SONIC study.

The association between serum uric acid (UA) and atherosclerosis in old people is controversial. Therefore, in this study, we clarified this association by assessing serum UA and common carotid atherosclerosis examined by carotid ultrasound in community-dwelling older people in their 70s, 80s and 90s in the SONIC study. A cross-sectional study was conducted involving 538 men and 577 women recruited from the community. The analysis was performed using serum UA as the explanatory variable and the maximum carotid intima-media thickness (max-CIMT) and mean-IMT as the dependent variables. The analysis was performed by multiple regression using traditional risk factors for atherosclerosis as adjustment variables. Analysis of the association between serum UA and IMT revealed a significant correlation only in women >70 years old. Max-CIMT (β = 0.081, 95% CI = 0.026, 0.136; P = 0.004) and mean-IMT (β = 0.015, 95% CI = 0.003, 0.029; P = 0.016) were significant. In the analysis of each age group, a significant correlation was only found in women in their 70s for mean-IMT (β = 0.031, 95% CI = 0.008, 0.053; P = 0.008). In community-dwelling women aged about 70 years old, elevated serum UA may be an independent risk factor for IMT thickening as a surrogate marker for atherosclerosis. Geriatr Gerontol Int 2021; 21: 94-101.

Homocysteine is Associated with the Development of Cerebral Small Vessel Disease: Retrospective Analyses from Neuroimaging and Cognitive Outcomes

ObjectiveAs the population ages, a growing burden of cerebral small vessel disease (cSVD) has sparked extensive concerns recently. Homocysteine (Hcy), as a traditional risk factor for atherosclerosis, may also participate in the development of cSVD. By comprehensively assessing Hcy's correlation with different MRI markers of cSVD and cognitive outcomes in a homogeneous population with cSVD, this study aims to explore the value of Hcy in the clinical management of cSVD. Methods231 inpatients with MRI-confirmed cSVD were enrolled in this retrospective study (mean age 66.4±10.0 years, male sex 47.6%). Along with brain MRI and plasma total Hcy (tHcy) examination, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were also performed to assess their global cognitive function. Burdens of cSVD neuroimaging features encompassing white matter hyperintensity (WMH), lacunes of presumed vascular origin, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS) were evaluated based on brain MRI demonstrations. ResultsAfter adjusting for possible confounders, statistical analyses showed that plasma tHcy levels were not only correlated with burdens of deep/periventricular WMH (P < 0.001, P for trend < 0.001; P < 0.001, P for trend < 0.001), lacunes (P < 0.001, P for trend < 0.001), lobar CMBs (P = 0.002), and EPVS in the basal ganglia (P < 0.001, P for trend = 0.002) but also remained an independent predictor of cognitive impairment (B=-0.159, 95%CI -0.269−-0.049, P = 0.005, P for trend < 0.001) in the patients with cSVD. ConclusionsPlasma tHcy levels are associated with the development of cSVD in a dose-independent manner and may predict the cognitive outcomes in cSVD patients. These findings provide a potential clue to cSVD's physiopathology and future disease management.

The Diagnostic Value of Radial and Carotid Intima Thickness Measured by High-Resolution Ultrasound for Ischemic Stroke

No study has examined intima thickness of the carotid artery and peripheral arteries in subjects with acute ischemic stroke due to large-artery atherosclerosis (LAAS). The aim of this study was to test whether carotid intima thickness (CIT), radial intima thickness (RIT), and dorsalis pedis intima thickness (PIT) are closely associated to atherosclerotic risk factors and whether they possess independent and additive value for differentiating LAAS stroke. One hundred and two patients with LAAS stroke and 104 age- and gender-matched control subjects were enrolled. CIT, RIT, and PIT were measured using a 24-MHz, high-resolution ultrasound system. Multivariate linear regression was performed to determine associations between ultrasonic parameters and risk factors. Binary logistic regression was used to evaluate the diagnostic value of different parameters. Receiver operating characteristic curves were plotted to compare the performance of several diagnostic models. CIT ([36.97±11.27]×10-2 vs [23.68±5.12]×10-2mm, P<.001) and RIT ([15.40±3.62]×10-2 vs [11.06±2.22]×10-2mm, P<.001) were significantly thicker in patients with LAAS stroke than in control subjects. CIT and RIT were associated with traditional risk factors for atherosclerosis, including age, systolic blood pressure, and serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, and glucose. CIT had incremental diagnostic value to traditional risk factors for LAAS stroke (area under the curve, 0.945 vs 0.860; P=.006). The addition of CIT and RIT to traditional risk factors had the best diagnostic performance (area under the curve, 0.961). Measurement of CIT, RIT, and PIT is feasible and reliable using newly developed ultrasound techniques. CIT and RIT were associated with traditional risk factors for atherosclerosis and exhibited incremental value to traditional risk factors for differentiating patients with LAAS stroke from control subjects.

Association of Baldness with Coronary Artery Disease and Its Severity

Background: The pivotal role of baldness as a potential risk factor for cardiovascular disorders remains a debate, and the small body of literature has generated inconsistent findings. We aimed to assess the association between baldness and the risk for coronary artery disease (CAD) and its severity in a sample of Iranian men. Materials and Methods: This cross-sectional study was performed on 105 consecutive patients suspected to CAD and scheduled for elective coronary angiography. The severity of CAD was determined according to the number of involved coronary vessels. For assessing the severity of baldness, the Hamilton-Norwood scale for grading of androgenetic alopecia in males was used. Results: The overall frequency of CAD in the groups with and without baldness was 88.9% and 72.5%, respectively, indicating a significant difference (P=0.033). Similarly, patients with the family history of baldness suffered more from CAD as compared to those without history (93.3% vs.76.0%). However, no significant association was found between the baldness and non-baldness groups with regard to the severity of CAD (P=0.291). According to the multivariable logistic regression model, the presence of baldness could predict the increased likelihood of CAD (or=3.037, P=0.046). Conclusion: Along with traditional risk factors for CAD, the presence of baldness and positive family history of this phenotype could be considered as the primary determinant for the increasing likelihood of CAD. [GMJ.2020;9:e1474]

Association of Baldness with Coronary Artery Disease and Its Severity.

Background: The pivotal role of baldness as a potential risk factor for cardiovascular disorders remains a debate, and the small body of literature has generated inconsistent findings. We aimed to assess the association between baldness and the risk for coronary artery disease (CAD) and its severity in a sample of Iranian men. Materials and Methods: This cross-sectional study was performed on 105 consecutive patients suspected to CAD and scheduled for elective coronary angiography. The severity of CAD was determined according to the number of involved coronary vessels. For assessing the severity of baldness, the Hamilton-Norwood scale for grading of androgenetic alopecia in males was used. Results: The overall frequency of CAD in the groups with and without baldness was 88.9% and 72.5%, respectively, indicating a significant difference (P=0.033). Similarly, patients with the family history of baldness suffered more from CAD as compared to those without history (93.3% vs.76.0%). However, no significant association was found between the baldness and non-baldness groups with regard to the severity of CAD (P=0.291). According to the multivariable logistic regression model, the presence of baldness could predict the increased likelihood of CAD (or=3.037, P=0.046). Conclusion: Along with traditional risk factors for CAD, the presence of baldness and positive family history of this phenotype could be considered as the primary determinant for the increasing likelihood of CAD.

Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

BackgroundPeripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.ObjectiveTo evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research design and methodsWe performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up.ResultsSortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72).ConclusionsThis study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

Pro-Atherogenic Inflammatory Mediators in Inflammatory Bowel Disease Patients Increase the Risk of Thrombosis, Coronary Artery Disease, and Myocardial Infarction: A Scientific Dilemma.

Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn’s disease, is characterized by widespread inflammation of the gastrointestinal tract with systemic manifestations. Inflammation is one of the driving forces for the pathogenesis of atherosclerosis and its dreaded complications like myocardial infarction (MI). Yet, the association between IBD and myocardial infarction has not been thoroughly established.Myocardial infarction in IBD patients was predominantly seen in young women during the active disease process. At the same time, elevated levels of C-reactive protein and other pro-inflammatory markers were observed in both IBD and atherosclerosis. Increasing evidence suggests inflammation inhibits fibrinolysis, expresses procoagulants, and suppresses anticoagulants promoting thrombosis formation. Moreover, the alteration of gut microbiota impacts the pathogenesis of inflammation and predisposes one to ischemic heart disease.Accordingly, all IBD patients should be screened and counseled on lifestyle modifications for the traditional risk factors of atherosclerosis. Future researchers should consider conducting more clinical trials on anti-inflammatory medication targeting atherosclerosis and therapeutics, while targeting the gut microbiota to reverse the inflammatory atherosclerotic process.

Is there any role of renin-angiotensin system inhibitors in modulating inflammatory bowel disease outcome?

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been associated with improved outcomes in inflammatory bowel disease. We aimed to investigate any possible effect of antihypertensive medications on inflammatory bowel disease course. One hundred and fifty inflammatory bowel disease patients with hypertension were compared using a 1:1 ratio with age- and gender-matched control patients with inflammatory bowel disease. The class of antihypertensive medication, traditional risk factors for atherosclerosis, inflammatory bowel disease characteristics, and history (surgery, hospitalizations, and treatment) were retrospectively analyzed. Of 150 (44.7% Crohn's disease) patients with hypertension, 46.7% were on angiotensin receptor blockers, 30.6% on angiotensin-converting enzyme inhibitors, 40% on β-blockers, and 40.7% on calcium channel blockers. Univariate analysis revealed significantly higher rates of traditional risk factors for atherosclerosis among antihypertensive users. When analyzing by class of antihypertensive medication, angiotensin receptor blockers were significantly associated with milder course as indicated by less frequent immunomodulator (P = 0.039) and steroid use (P = 0.041). Rates of lifetime steroids were statistically significantly lower among angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio = 1.191, 95% confidence interval, 1.005-1.411). After adjustment with confounding factors, only angiotensin receptor blockers were associated with milder inflammatory bowel disease course (P = 0.037) and lower rates of immunomodulator use (P = 0.038). Our study suggests a possible protective effect of angiotensin receptor blockers on overall inflammatory bowel disease course by targeting the renin-angiotensin system. Their effect on inflammatory bowel disease needs to be studied in larger cohorts.

Serum asymmetric dimethylarginine, a novel risk marker of coronary artery disease

Coronary artery disease (CAD) is a chronic disease and a global health problem, affecting one-third of the world’s population. Recently it has been found that the traditional risk factors of CAD do not account for the total risk. One of the novel risk markers of CAD is Asymmetric dimethylarginine (ADMA), which inhibits the enzyme nitric oxide synthase (NOS), which is required for the synthesis of nitric oxide (NO), a potent vasodilator. Increased ADMA level causes decrease in NO level which will lead to endothelial dysfunction, an underlying causative mechanism for CAD development. ADMA is found to be an independent cardiovascular risk factor. Therefore ADMA may become an additional biochemical parameter to identify those patients who are at higher risk for developing CAD, besides the traditional parameters used.To study the association between serum ADMA level with coronary artery disease.The study design is a case-control study. 80 subjects from the south Indian population between 30 to 60 years of age, of both the sexes were included in the study. Out of them, 40 individuals were angiographically proven cases of CAD from the department of cardiology and 40 healthy individuals from the master health check up department. Various parameters like lipid profile, serum ADMA, blood pressure and BMI were measured in both the groups. The data were collected and analyzed.The ADMA level was found to be significantly elevated in the case group compared with the age matched healthy controls (p value &amp;#60; 0.05).There is a positive correlation between serum ADMA level and coronary artery disease.

Genetic risk scores for coronary artery disease and its traditional risk factors: Their role in the progression of coronary artery calcification-Results of the Heinz Nixdorf Recall study.

BackgroundAtherosclerosis is the primary cause of coronary artery disease (CAD). Several observational studies have examined the association of traditional CAD risk factors with the progression of coronary artery calcification (CAC). In our study we investigated the effect of 11 different genetic risk scores associated with CAD and CAD risk factors on the progression of CAC.Methods and resultsWe included 3097 participants from the Heinz Nixdorf Recall study who had available CAC measurements at baseline (CACb) and at the 5-year follow-up (CAC5y). A weighted genetic risk score for CAD and each of the CAD-associated risk factors was constructed. Multiple regression analyses were applied to i) the difference between the observed log(CAC5y+1) (log(obs)) and expected log(CAC5y+1) (log(exp)) at the 5-year follow-up following the individual’s log(CACb+1) percentile for the time between scans (log(obs)–log(exp)) and ii) the 5-year CAC progression, defined as 5*(log(CAC5y+1)–log(CACb+1))/time between the scans, adjusted for age, sex, and log(CACb+1) as well as for risk factors. The median percent deviation from the expected (CAC5y+1) and the 5-year progression of (CAC+1) in our study were 0 (first quartile: Q1; third quartile: Q3: -0.32; 0.48) and 45.4% (0%; 171.0%) respectively. In the age-, sex- and log(CACb+1)-adjusted model, the per-standard deviation (SD) increase in CAD genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (9.7% (95% confidence interval: 5.2%; 14.5%), p = 1.6x10-5) and the 5-year progression of CAC (7.1% (3.0%; 11.4%), p = 0.0005). The CAD genetic risk score explains an additional 0.6% of the observed phenotypic variance for “log(obs)–log(exp)” and 0.4% for 5-year progression of CAC. Additionally, the per-SD increase in the CAC genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (6.2% (1.9%; 10.8%, p = 0.005)) explaining an additional 0.2% of the observed phenotypic variance. However, the per-SD increase in the CAC genetic risk score was not associated with the 5-year progression of CAC (4.4% (0.4%; 8.5%), p = 0.03) after multiple testing. Adjusting for risk factors did not change the results. None of the other genetic risk scores showed an association with the percent deviation from the expected (CAC5y+1) or with the 5-year progression of CAC.ConclusionsThe association of the CAC genetic risk score and the CAD genetic risk score provides evidence that genetic determinants for CAC and CAD influence the progression of CAC.

Plasma lipids in patients with inflammatory bowel disease : Observations on the associations between lipid indices and coronary flow reserve.

Patients with inflammatory bowel disease (IBD) are at increased risk for coronary artery disease (CAD), even after adjusting for traditional risk factors for atherosclerosis. While inflammation is widely regarded as the pathophysiologic link between IBD and CAD, the exact mechanisms are largely unknown. This study was conducted to investigate the association of lipid parameters and indices with coronary flow reserve and markers of inflammation in IBD patients. Atotal of 73patients with IBD and 26healthy controls were enrolled. Patients in the IBD arm were either in remission or had mild disease activity. Lipid parameters, C‑reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were analyzed using standard laboratory techniques. Coronary flow reserve (CFR) was measured using two-dimensional echocardiography. Both CRP and ESR were higher and CFR was significantly lower in IBD patients, but there were no differences in terms of lipid parameters or indices; however, patients with IBD and aCFR <2.0 had significantly higher triglyceride (TG) level (155.0 (80.0) mg/dl vs. 108.0 (68.0) mg/dl, p < 0.001) and there was astrong trend towards lower high-density lipoprotein (HDL) cholesterol (40.0 (8.5) mg/dl vs. 45.0 (10.0) mg/dl, p = 0.05) level in the latter group when compared to patients with aCFR ≥2.0. The atherogenic index of plasma (AIP), measured as log(TG/HDL-C) had the best predictive value for CFR in IBD group and was an independent predictor of CFR after multivariate adjustment for confounders (unstandardized coefficient: -0.75, 95% CI: (-1.13)-(-0.37)), β = -0.41, p = <0.001). The atherogenic index of plasma is amarker for reduced CFR in IBD patients and could be useful to screen those at risk for early atherogenesis and CAD.

Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide.

The increasing prevalence of cardiovascular diseases cannot adequately be explained by traditional risk factors. Recently, accumulating evidence has suggested that gut microbiota‐derived numerous metabolites are contributors to atherosclerotic events. Among them, the role of trimethylamine N‐oxide (TMAO) in promoting atherosclerosis has gained attention. TMAO is reported to exert the proatherogenic effects by impacting on the traditional risk factors of atherosclerosis and is associated with high risk of cardiovascular events. Besides that, TMAO is involved in the complex pathological processes of atherosclerotic lesion formation, such as endothelial dysfunction, platelet activation and thrombus generation. In light of these promising findings, TMAO may serve as a potential target for atherosclerosis prevention and treatment, which is conceptually novel, when compared with existing traditional treatments. It is likely that regulating TMAO production and associated gut microbiota may become a promising strategy for the anti‐atherosclerosis therapy.