Lifetime marijuana use and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study

Background: Coronary artery calcification (CAC) and carotid intima-media thickness (CIMT), established measures of subclinical atherosclerosis, that have been demonstrated to improve prediction of coronary artery disease (CAD) risk beyond classical risk factors (CRFs). This study examined the epigenetic mechanisms underlying the appearance of CAC and increased CIMT, which have not been previously explored. Methods: We conducted an epigenome-wide association study (EWAS) in 46 non-smoking and non-diabetic white subjects randomly selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CAC and CIMT were measured by computed tomography (CT) and catotid artery ultrasound at examination year (Y) 20. The Illumina HumanMethylation450 BeadChip was used to measure DNA methylation in white blood cells collected at Y15. We dropped one sample with >1% of the CpG sites having a detection p-value >0.05 and then exclude ~160k CpG probes due to their ambiguously mapping to the genome or with the presence of common SNPs, etc. Both background adjustment and normalization were performed separately for Infinium I and II probes, and new values were calculated and then transformed into M-values. After correction for potential chip effect, we examined the associations between these pre-processed methylation levels at each CpG site with CAC and CIMT using multiple logistic and linear regression models, respectively. Pathway analysis was performed to explore the gene sets that were significantly associated with CAC and CIMT. Results: Several CpG sites in multiple genes were significantly associated with CAC or CIMT. Some of these genes play roles in the regulation of vascular function, such as ion binding and transport ( HRH1 , LRP1B , KCNJ9 , TRIM40 , ADAMTS3 for CAC and BRSK2 , ZNF428 , TROVE2 , C1orf86 for CIMT) and metabolic processes ( LEPR for CAC and NUP50 for CIMT). Pathway analyses revealed several common canonical pathways for CAC and CIMT including, calcium signaling, axon guidance, and focal adhesion etc., which are relevant to the occurrence of these two subclinical CADs. The statistical significance of identified CpG sties for either CAC or CIMT did not remain after correction for multiple testing, possibly due to the small sample size. Conclusion: Our preliminary findings suggest that methylomic mechanisms may play a role in the development of CAC and CIMT, and subsequently the etiology of CAD. Future replication studies in larger longitudinally studies are needed.

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Abstract P404: Coronary Artery Calcification Presence and Progression by Obesity Phenotypes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽

10.1161/circ.141.suppl_1.p404 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Sarah M Camhi ◽

Aviva Must ◽

Philimon N Gona ◽

Arlene Hankinson ◽

Andrew O Odegaard ◽

...

Keyword(s):

Young Adults ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Subclinical Atherosclerosis ◽

Past Research ◽

Dichotomous Variable ◽

Research Findings ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity ◽

Insight Into

Background: Past research findings regarding whether metabolically healthy obesity (MHO) is a healthier state within obesity have been mixed and often controversial. Coronary artery calcification (CAC) can provide insight into subclinical atherosclerosis burden and progression. The purpose of this study was to compare CAC presence and progression between non-obese and obese phenotypes (MHO and metabolically unhealthy obesity, MUO). Methods: Young adults (18-30 years of age in 1985-86) enrolled in the CARDIA study were excluded if they had baseline obesity, had undergone bariatric surgery or were pregnant/breastfeeding. CAC was estimated with computed tomography using standardized procedures at all coronary arteries and summed across all arteries at year (Y) Y15 and Y25 (Agatston units, AU). Presence of CAC (n=2546) was defined as any score >0 AU at Y15. Progression of CAC (ΔCAC, n=2035) was a dichotomous variable indicating any incident CAC at Y25 for participants without CAC at Y15 or an increase in CAC ≥20 AU from Y15-Y25. Obesity onset (BMI ≥30 kg/m 2 ) was identified at Y7, Y10, Y15. MHO was defined as obesity and 0-1 risk factor: SBP/DBP ≥130/85mmHg; glucose ≥100mg/dL; triglycerides ≥150mg/dL; and HDL-C men <40, women <50mg/dL or on relevant medication. MUO was defined as obesity and ≥2 risk factors. MHO duration was estimated as years from identification of MHO to either Y15 or transition to MUO. Phenotypes were categorized by MHO duration (MHO duration×obesity duration): stable MHO (100%); transient MHO (1-99%); MUO (0%). Logistic regression analysis was used to estimate the odds of CAC presence or ΔCAC between obesity phenotypes adjusting for age, sex, race, smoking, alcohol and physical activity. Results: Participants were 42% black and 52% female, 25.2±3.6 years at baseline with BMI 23.3±2.9 kg/m 2 at baseline, and BMI 27.4±5.1 kg/m 2 at Y15. CAC presence was 9% (n=173) among non-obese (n=1849); 6% (n=23) among stable MHO (n=373), 10% (n=12) among transient MHO (n=115), and 1% (n=39) among MUO (n=209). ΔCAC was 26% (385/1467), 18% (54/298), 31% (31/100) and 46% 79/170) for non-obese, stable MHO, transient MHO and MUO, respectively. Compared to stable MHO, MUO had higher odds of CAC presence (OR, 95% CI: 3.26, 1.73-6.15) and ΔCAC (3.30, 2.14-5.11); transient MHO had higher odds of ΔCAC (1.88, 1.10-3.20); with no significant differences between transient MHO vs. stable MHO for CAC presence. There were also no significant differences between non-obese and stable MHO for either CAC presence or ΔCAC. Among those who developed obesity, each additional 5 years of MHO duration was associated with lower odds of ΔCAC (0.60, 0.46-0.78). Conclusion: Our findings suggest that subclinical coronary calcified atherosclerosis burden is similar for non-obese and stable MHO, and higher in MUO vs. non-obese. Future studies should confirm results and examine possible biological mechanisms.

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Procoagulants and Subclinical Atherosclerosis in Young Adults: The CARDIA Study.

Blood ◽

10.1182/blood.v114.22.2973.2973 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2973-2973

Author(s):

David Green ◽

Nancy Foiles ◽

Cheeling Chan ◽

Joseph Kang ◽

Pamela Schreiner ◽

...

Keyword(s):

Young Adults ◽

Coronary Artery ◽

Conflicts Of Interest ◽

Subclinical Atherosclerosis ◽

Clotting Factors ◽

Cross Sectional ◽

Total Group ◽

Subclinical Disease ◽

The Common ◽

Prospective Analyses

Abstract Abstract 2973 Poster Board II-948 Background: Elevated levels of procoagulants (FVII, FVIII, vWF) have been associated with cardiovascular disease, but whether they play a role in atherogenesis is unclear. Study of these factors in young adulthood, prior to clinically manifested disease, and years later when subclinical atherosclerosis has developed, might clarify these associations. The Coronary Artery Risk Development in Young Adults (CARDIA) Study provides an opportunity to examine this issue. Methods: Assays of FVII, FVIII, and vWF were performed in 1255 participants ages 23-37 (Year 7,Y7) and repeated at ages 38-50 (Year 20,Y20). Coronary artery calcification (CAC) prevalence and mean intimal-medial thickness (IMT) in the common carotid (CC) and internal carotid (IC) were measured at Y20. Prospective (Y7 clotting factors, Y20 CAC & IMT) and cross-sectional (Y20 clotting factors, Y20 CAC & IMT) analyses were performed. We also grouped participants according to whether they had one or more procoagulants in the highest tertile at Y7, Y20, or both, and evaluated their associations with subclinical disease. Results: Y7 levels of procoagulants (%), mean(SD) were: FVII 76(18), FVIII 102(38), and vWF 108(47). At Y20, all had increased by 40% to 55%, and CAC>0 was present in 20% of participants. After adjustment for age, the prospective analyses showed a trend of progressively greater CC thickness from the lowest to the highest tertile of FVII activity in the total group (P=0.007) and in whites (P=0.002) and men (P=0.015). Associations of FVII with IC thickness (0.82 mm to 0.84 mm) and the prevalence of CAC (18.6% to 23%) were weaker (P-trend, 0.1-0.3). Higher FVIII levels were associated with greater IC thickness in the total group, in whites, and in women (highest vs lowest tertile, P<0.05 for each comparison). No associations were seen with vWF. Cross-sectional analyses confirmed the association between FVII and carotid thickening, most strongly with the CC (P=0.002). Most associations were attenuated by multivariable adjustment (BMI, smoking, education, blood pressure, cholesterol, & CRP). Participants with FVII values in the highest tertile at Y7, Y20, or both had a higher prevalence of CAC and greater carotid thickening than those with values in the lowest tertile (P<0.05). Such associations were not observed with FVIII or vWF. Conclusion: FVII is a marker but not an independent risk factor for future atherosclerosis in young adults; FVIII is associated with IC thickening, and no associations were observed for vWF. Disclosures: No relevant conflicts of interest to declare.

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VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY IN EARLY ADULTHOOD AND SUBCLINICAL ATHEROSCLEROSIS AND ARTERIAL WALL THICKNESS BY MIDDLE AGE: THE CORONARY ARTERY RISK DEVELOPMENT IN YOUNG ADULTS (CARDIA) STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)32678-4 ◽

2020 ◽

Vol 75 (11) ◽

pp. 2051

Author(s):

Chike Nwabuo ◽

Yuichiro Yano ◽

Henrique Moreira ◽

Duke Appiah ◽

Henrique Vasconcellos ◽

...

Keyword(s):

Blood Pressure ◽

Young Adults ◽

Coronary Artery ◽

Wall Thickness ◽

Blood Pressure Variability ◽

Arterial Wall ◽

Middle Age ◽

Subclinical Atherosclerosis ◽

Early Adulthood ◽

Arterial Wall Thickness

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Abstract MP72: Apolipoprotein B and Apolipoprotein B, LDL-C Discordance in Young Adults Are Associated With Coronary Artery Calcification at 25 Year Follow-Up: The Coronary Artery Disease in Young Adults (CARDIA) Study

Circulation ◽

10.1161/circ.129.suppl_1.mp72 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Ron C Li ◽

Cheeling Chan ◽

Allan Sniderman ◽

Kiang Liu ◽

Donald Lloyd-Jones ◽

...

Keyword(s):

Risk Factors ◽

Young Adults ◽

Risk Factor ◽

Coronary Artery ◽

Apolipoprotein B ◽

Subclinical Atherosclerosis ◽

Agatston Score ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Increased Risk

Introduction: High ApoB has been shown to predict cardiovascular disease (CVD) in adults even in the context of low LDL-C. It is not known, however, if high ApoB and high ApoB, low LDL-C discordance in young adults are associated with coronary artery calcium (CAC) in mid-life. Methods: Data were derived from CARDIA, a multicenter study of the development and determinants of CVD risk factors in young adults recruited at ages 18 to 30. All participants with complete baseline CVD risk factor data, ApoB, and year-25 CAC score were included in this study. Baseline lipid fractions and ApoB were measured by standard assays. Year-25 CAC was assessed using two consecutive CT scans with presence of CAC defined as having a positive, non-zero Agatston score using the average of two scans. Baseline ApoB values were divided into tertiles. Four mutually exclusive concordant/discordant groups were created based on median ApoB and LDL-C. Logistic regression was performed for unadjusted and adjusted models. Results: 3496 participants were included [mean age=25±3.6, BMI=24.5±5Kg/m2, 44.4% male, and the following mean lipid values (mg/dL): total cholesterol=177.3±33.1, LDL-C=109.9±31.1, HDL-C=53±12.8, ApoB=90.7±24, median triglycerides=61(IQR 46-83)]. Compared with the lowest ApoB tertile, the middle [OR=1.55 (95% CI 1.22-1.95)] and high [OR=2.35 (95% CI 1.87-2.97)] tertiles exhibited increased odds of developing year-25 CAC in traditional risk factor-adjusted models. High ApoB, low LDL-C discordance was also associated with year-25 CAC in adjusted models [OR=1.57 (95% CI 1.12-2.20)]. Conclusions: These data suggest a dose-response association between ApoB in young adults and presence of mid-life CAC independent of baseline traditional CVD risk factors. High ApoB, low LDL-C discordance was also associated with year-25 CAC, suggesting that ApoB in young adults may help identify individuals with modest LDL-C levels who are at increased risk for subclinical atherosclerosis in mid-life.

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