Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health).

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Increased GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy participants. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and 2 interval CAC assessments between 2010 and 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC >0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were women, and 54.6% and 16.1% (429 of 2,690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 µmol/L, and the incidence of CAC was 13.1% (280 of 2,129). The GlycA level odds ratio for CAC incidence was 1.002 (95% confidence interval 1.0005 to 1.005, p = 0.016), adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and co-morbidities. The GlycA (≤p25 vs ≥p75) odds ratio for CAC progression (Berry definition) was 1.77 (95% confidence interval 1.07 to 2.96, p = 0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as β (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (β, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as ß (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (ß, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing.

PURPOSE OF REVIEW: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies. RECENT FINDINGS: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

Increased Carotid Intima-Media Thickness in Asymptomatic Individuals Is Associated with the PCSK9 (rs2149041) Gene Polymorphism in the Mexican Mestizo Population: Results of the GEA Cohort.

The increase in carotid intima-media thickness (CIMT) and coronary artery calcification (CAC) are features of subclinical atherosclerosis that might be determined by the genetic background of patients. Among the multiple risk factors, the proprotein convertase subtilisin kexin type 9 (PCSK9) has a great impact on atheroma development. Then, we focused on the potential association of the PCSK9 gene polymorphism (rs2149041) with the risk of an increased CIMT. We included 881 unrelated, asymptomatic individuals (732 normal CIMT and 149 increased CIMT) who lacked coronary calcification (CAC score = 0). Under the recessive inheritance model and adjusted by several cardiovascular risk factors, the rs2149041 polymorphism, determined by TaqMan genotyping assay, was associated with a high risk of increased CIMT (OR = 2.10, 95% IC = 1.26-3.47, P recessive = 0.004). Our results suggest that the rs2149041 polymorphism could be a risk marker for increased CIMT in asymptomatic individuals without coronary artery disease determined by the absence of a CAC score.

Association between phase angle and coronary artery calcium score in patients on peritoneal dialysis.

Introduction: The phase angle (PhA) has been used as a nutritional marker and predictor of mortality in patients on peritoneal dialysis (PD). The coronary artery calcium (CAC) score has shown to predict the incidence of acute myocardial infarction and death from cardiovascular disease in these patients. However, the association between PhA and CAC score in patients with PD is not well-established, which is the objective of this study. Materials and methods: Cross-sectional study with patients on PD, followed up at a University Hospital, between March 2018 and August 2019. PhA was evaluated by unifrequency bioimpedance (BIA). The CAC score was calculated based on cardiovascular computed tomography, considering positive when greater than or equal to 100 Agatston and negative when less than 100 Agatston. Results: We evaluated 44 patients on dialysis, with a mean age of 56 years and median time on dialysis therapy was 11.7 months. In the statistical analysis, a significant association was only observed between the CAC score and the PhA. Conclusion: The PhA is associated with a positive CAC score in patients with PD, and despite other factors, may be useful as a risk marker for coronary artery disease in this population.

Custo-Efetividade do Emprego do Escore de Cálcio Coronariano na Orientação para a Decisão Terapêutica na Prevenção Primária, na População Brasileira / Cost-Effectiveness of Using the Coronary Artery Calcium Score in Guiding Therapeutic Decisions in Primary Prevention in the Brazilian Population

Resumo Fundamento: O emprego do escore de cálcio no auxílio da estratificação de risco cardiovascular pode ser ferramenta com melhor custo-efetividade em comparação à estratégia convencional. Objetivos: Avaliação da custo-efetividade do emprego do escore de cálcio na orientação terapêutica para a prevenção primária cardiovascular. Métodos: Modelo de microssimulação para avaliar as consequências clínicas e econômicas da doença cardiovascular aterosclerótica, comparando-se a estratégia de prevenção pelo uso do escore de cálcio e a estratégia convencional. Resultados: Resultados obtidos demonstram melhor custo-efetividade da estratégia terapêutica guiada pelo escore de cálcio, por meio da redução do custo incremental, e aumento nos anos de vida ajustados por qualidade (QALY), que corresponde, em número, ao benefício incorporado à qualidade de vida do indivíduo. Conclusões: O emprego do escore de cálcio mostrou-se mais custo-efetivo que a estratégia convencional tanto em custo como em QALY, na maioria dos cenários estudados.

Abstract Background: The use of the coronary artery calcium score to aid cardiovascular risk stratification may be a more cost-effective tool than the conventional strategy. Objectives: Evaluation of the cost-effectiveness of the use of the calcium score in therapeutic guidance for primary cardiovascular prevention. Methods: A microsimulation model to assess the clinical and economic consequences of atherosclerotic cardiovascular disease, comparing the prevention strategy using the calcium score and the conventional strategy. Results: The results obtained demonstrated a better cost-effectiveness of the therapeutic strategy guided by the calcium score, by reducing incremental costs and increasing quality-adjusted life years (QALY), which corresponds, in number, to improving the quality of life of the individual. Conclusions: The use of the coronary artery calcium score proved to be more cost-effective than the conventional strategy, both in terms of cost and QALY, in most of the scenarios studied.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil.

OBJECTIVES: This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. METHODS: A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. RESULTS: The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. CONCLUSIONS: The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Cardiovascular risk assessment by coronary artery calcium score in subjects with maturity-onset diabetes of the young caused by glucokinase mutations.

AIMS: Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. MATERIALS AND METHODS: Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. RESULTS: Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CONCLUSIONS: CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.

Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project.

BACKGROUND: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. METHODS: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). RESULTS: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. CONCLUSIONS: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

Choosing between anatomy and function is not always evident for the heart of end-stage renal disease patients. How low can we go?

Patients with chronic kidney disease (CKD) are at a very high risk of adverse cardiovascular events. In CKD patients, vascular calcification is more prevalent, appears at an earlier age, and is more severe than in the general population. CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease in these patients. Considering the significant morbidity and mortality attributable to cardiovascular disease in the CKD population, risk stratification remains an important challenge. Topics such as function vs anatomy to properly risk stratify these patients, as well as future perspectives on non-invasive techniques, will be addressed.

Predictors of coronary artery calcium incidence and progression: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: There are limited data on serial coronary artery calcium (CAC) assessments outside North American and European populations. We sought to investigate risk factors for CAC incidence and progression in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: We included individuals with no prior cardiovascular disease and two CAC measurements in ELSA-Brasil. Incident CAC was defined as a baseline CAC of 0 followed by CAC >0 on the second study. CAC progression was defined according to multiple published criteria. We performed logistic and linear regression to identify risk factors for CAC incidence and progression. We also examined risk factor effect modification by baseline CAC (0 vs. >0). RESULTS: A total of 2707 individuals were included (57% women, age 48.6 ± 7.7 years). Participants self-identified as white (55%), brown (24%), black (16%), Asian (4%) and Indigenous (1%). The mean period between CAC assessments was 5.1 ± 0.9 years. CAC incidence occurred in 282 (13.3%) of 2127 individuals with baseline CAC of 0. CAC progression occurred in 319 (55%) of 580 participants with baseline CAC >0. Risk factors for CAC incidence included older age, male sex, white race, hypertension, diabetes, higher BMI, smoking, lower HDL-C, higher LDL-C and triglycerides, and metabolic syndrome. Older age and elevated LDL-C were associated with CAC incidence, but not progression. Risk factors consistently associated with CAC progression were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome. On interaction testing, these four risk factors were more strongly associated with CAC progression as compared to CAC incidence. CONCLUSIONS: CAC incidence was associated with multiple traditional risk factors, whereas the only risk factors associated with progression of CAC were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome.

The association of waist-to-height ratio and other anthropometric measurements with subclinical atherosclerosis: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: To compare the performance of waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), waist circumference (WC) and Body-mass index (BMI) with subclinical atherosclerosis. METHODS AND RESULTS: The association of quintiles of anthropometric variables (1st as reference) - Odds ratio (OR); 95% Confidence Interval (95% CI) - with Coronary Artery Calcium (CAC: 0 vs. >0; <100 vs. ≥100), Carotid Intima-Media Thickness (CIMT: <75th vs. ≥P75%) and as continuous variables in linear regression models in 4216 participants of ELSA-Brasil baseline. WHtR was associated with CAC >0 (OR, 1.84; 95% CI, 1.16-2.93) and ≥100 after multivariate adjustment including BMI. WHR was associated with CAC >0 OR, 1.81 (95% CI, 1.25-2.82) and ≥100. BMI was not associated with CAC after further adjustment for WHtR, but was associated with CAC >0 after adjustment for WHR (OR, 1.42; 95% CI, 1.02-1.94) or WC (1.63; 95% CI, 1.03-2.59). WHtR was not associated with CIMT after further adjustment for BMI. WHR was associated with CIMT ≥P75% (OR, 1.44; 95% CI, 1.02-2.02) and in linear models (p < 0.0001). WC was associated with CIMT in linear models (p < 0.0001). BMI was associated to CIMT ≥P75% (OR, 2.25; 95% CI, 1.53-2.54); and in linear models (P < 0.0001) after further adjustment for WHtR. After adjustment for WHR and WC the association of BMI with CIMT ≥P75% was respectively (OR 2.31; 95% CI, 1.70-3.13; and OR 2.39; 95% CI, 1.55-3.70); and in both linear models (p < 0.0001). CONCLUSIONS: WHtR was a good biomarker for subclinical atherosclerosis measured by CAC while BMI was a good biomarker for CIMT. WHR presented the best performance being associated with both biomarkers of subclinical atherosclerosis.

The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers: Brazilian Longitudinal Study of Adult Health.

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.

Composite acute phase glycoproteins with coronary artery calcification depends on metabolic syndrome presence - The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Inflammation has been weakly associated with coronary artery calcium (CAC) in the overall population. However, it is currently unknown whether this varies according to the cardio-metabolic profile. We evaluated the association between GlycA, a unique composite biomarker of pro-inflammatory acute phase glycoproteins, high sensitivity C-reactive protein (hsCRP), uric acid, and their composite values (composite inflammation) in the overall population and strata according to cardiovascular risk. METHODS: This is a cross-sectional study of 3753 Sao Paulo site participants of the ELSA-Brasil cohort that were free of cardiovascular/chronic inflammatory disease and not taking statins or allopurinol. We measured GlycA by nuclear magnetic resonance spectroscopy. For each biomarker quartile (Qs), we ran adjusted logistic and linear regression for CAC>0 and CAC score. RESULTS: In the overall analysis, the 4th vs. 1st GlycA Q odds ratio (OR) for CAC>0 was 1.53 (95% CI: 1.18, 1.98, p trend<0.001) adjusted for demographics and lifestyle, but null after adding metabolic syndrome (MS) components, OR 1.14 (95% CI: 0.86, 1.51, p trend=0.140). Likewise, for continuous CAC values there was no difference across GlycA Qs in the fully adjusted analysis. Similarly, hsCRP, uric acid, and composite inflammation were not associated with CAC>0 or CAC score. In stratified analysis, GlycA was associated with CAC>0 in No-MS individuals, standardized (SD) OR 1.23 (95% CI: 1.08, 1.40); but not in MS individuals, SD OR 1.01 (95% CI: 0.89, 1.15) (p interaction 0.037). We found similar interaction in stratified analysis for continuous CAC on composite inflammation. CONCLUSIONS: GlycA and composite inflammation are associated with CAC among low cardiovascular risk individuals (No-MS), but not otherwise. GlycA and composite biomarkers may better represent sources of inflammation apart from visceral obesity and traditional cardiovascular risk factors, which may have relevant effect on CAC accumulation in low cardiovascular risk individuals.