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Genetic Profiling Using Genome-Wide Significant Coronary Artery Disease Risk Variants Does Not Improve the Prediction of Subclinical Atherosclerosis: The Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey – A Meta-Analysis of Three Independent Studies  [PDF]
Jussi A. Hernesniemi, Ilkka Sepp?l?, Leo-Pekka Lyytik?inen, Nina Mononen, Niku Oksala, Nina Hutri-K?h?nen, Markus Juonala, Leena Taittonen, Erin N. Smith, Nicholas J. Schork, Wei Chen, Sathanur R. Srinivasan, Gerald S. Berenson, Sarah S. Murray, Tomi Laitinen, Antti Jula, Johannes Kettunen, Samuli Ripatti, Reijo Laaksonen, Jorma Viikari, Mika K?h?nen, Olli T. Raitakari, Terho Lehtim?ki
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0028931
Abstract: Background Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis – i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE) – beyond classical risk factors. Subjects and Methods We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30–45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46–76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS24SNP/CAD) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up. Results CIMT or CAE did not significantly associate with GRS24SNP/CAD before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta-analysis CIMT or CAE did not associate with any of the SNPs. Conclusion Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults.
Subclinical hypothyroidism and risk to carotid atherosclerosis
Valentina, Velkoska Nakova;Marijan, Bosevski;Chedo, Dimitrovski;Branka, Krstevska;
Arquivos Brasileiros de Endocrinologia & Metabologia , 2011, DOI: 10.1590/S0004-27302011000700007
Abstract: objective: the aim of this study was to assess whether subclinical hypothyroidism (sch) is associated with carotid atherosclerosis, as well as dyslipidemia, and arterial hypertension. subjects and methods: the study included 69 consecutive patients with newly diagnosed sch, and 30 matched healthy controls. body mass index (bmi), tsh, ft4, antibodies to thyroid peroxidase (tpoabs), lipids, blood pressure, mean and maximum carotid intima-media thickness (cimt) were determined in all participants. results: mean values of cimt, triglycerides, and total cholesterol/hdl-c ratio were significantly different in sch patients versus matched controls. linear multiple regression analysis demonstrated that tsh, diastolic blood pressure and triglycerides were independent predictors of mean cimt, ft4 for maximum cimt; and that tsh, ft4, age, and total cholesterol/hdl-c ratio were independent predictors of the presence of carotid plaques. conclusion: our data revealed that sch is associated with increase in cimt and presence of carotid plaques, independent of classical risk factors for atherosclerosis.
Subclinical carotid atherosclerosis and cardiovascular risk factors in HIV-infected patients  [PDF]
Wies?awa Kwiatkowska,Brygida Knysz,Justyna Drelichowska-Durawa,Marcin Czarnecki
Post?py Higieny i Medycyny Do?wiadczalnej , 2011,
Abstract: Background:HIV infected patients, especially those treated with antiretroviral (ARV) drugs, show an increased risk and incidence of cardiovascular disease.Objectives:The aim of this study was to evaluate the progression of subclinical atherosclerosis in the carotid arteries, expressed as the value of carotid intima-media thickness (cIMT) and the amount of atherosclerotic plaques, and to analyze the correlation between cIMT and risk factors for cardiovascular diseases in a cohort of HIV infected patients.Methods:The analysis included 72 HIV infected patients, mean age 39.4 years, and 27 healthy HIV negative individuals, matched for age and sex. The data collected included evaluation of the infection, ARV treatment, past cardiovascular events, assessment of traditional and nontraditional risk factors for cardiovascular diseases, cIMT measurements and amount of atherosclerotic plaques in the carotid arteries.Results:HIV infected patients show more advanced subclinical atherosclerosis in the carotid arteries (cIMT and plaques incidence). The cardiovascular risk profile of the HIV infected patients is significantly different from HIV negative people. Among the HIV positive group lower body mass index (BMI) and higher waist/hip ratio (WHR) are observed. The concentration of all cholesterol fractions is lower, whereas the concentration of triglycerides is higher. Cigarette smoking is more common among HIV-infected individuals. A strong statistical correlation between cIMT and age, hypertension, non-high-density lipoprotein (non-HDL) cholesterol and ARV time were found. Total and LDL cholesterol, and lifetime smoking exposure also affect the cIMT. The relationship between cIMT and current HIV RNA may indicate the impact of the current infection status on the cIMT dynamics in this subpopulation.
Subclinical atherosclerosis in northern and southern China:the Chinese paradox
Jie Huang,Yang-Feng Wu,Xiao-Qing Liu,Ding Ding
老年心脏病学杂志(英文版) , 2011,
Abstract: Background The incidence of coronary heart disease (CHD) is higher in Northern than that in Southern China, however differences in traditional CHD risk factors do not fully explain this. No study has examined the differences in subclinical atherosclerosis that may help explain the differences in incidence. This study examined these differences in subclinical atherosclerosis using coronary computed tomography (CT) for calcification between the Northern and Southern China. Methods We selected a random sample of participants in a large multi-center ongoing epidemiologic study for coronary calcium scanning in one northern city (North) (Beijing, n = 49) and in two southern cities (South) (Shanghai, n = 50, and Guangzhou, n = 50). Participants from the three field centers (mean age 67 years) underwent coronary risk factor evaluation and cardiac CT scanning for coronary calcium measurement using the Multi-Ethnic Study of Atherosclerosis scanning protocol. Results Adjusted log-transformed coronary artery calcium score in North China (Beijing) was 3.1 +/-0.4 and in South China (Shanghai and Guangzhou) was 2.2 +/- 0.3 (P = 0.04). Mean calcium score for the northern city of Beijing was three times higher than that of the southern city of Guangzhou (P = 0.01) and 2.5 times higher than for the southern city of Shanghai (P = 0.03). Conclusions The extent of subclinical atherosclerosis is significantly higher in the northern city of Beijing than that in the two southern cities of Guangzhou and Shanghai, even after adjusting for standard cardiac risk factors. This finding suggests that standard risk factors do not fully explain north south differences in clinical CHD incidence.
Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders
Elisabetta Profumo,Manuela Di Franco,Brigitta Buttari,Roberta Masella,Carmelina Filesi,Maria Elena Tosti,Rossana Scrivo,Antongiulio Scarno,Antonio Spadaro,Luciano Saso,Rachele Riganò
Mediators of Inflammation , 2012, DOI: 10.1155/2012/503942
Abstract: Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.
The Association between Subclinical Atherosclerosis and Uterine Fibroids  [PDF]
Yuan He, Qiang Zeng, Xiaohui Li, Baohua Liu, Peiyu Wang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057089
Abstract: Objective(s) To explore the atherogenic hypothesis of uterine fibroids among Chinese women. Methods In a case-control study, 335 patients confirmed by ultrasound or hysterectomy surgery and 539 controls were enrolled between October 1, 2009 and April 1, 2012. Unconditional logistic regressions were used to calculate the odds ratios (ORs) for the associations of subclinical atherogenic and cardiovascular risk parameters with uterine fibroids in the overall case group and hysterectomy-confirmed case group, respectively. Results Higher level of ankle-brachial index (ABI) was independently associated with increased odds of uterine fibroids. The odds of UF among women in the highest tertile of ABI were 1.88 times higher (95%CI: 1.17, 3.02, Ptrend = 0.008) compared to those in the lowest tertile. The serum concentration of homocysteine was inversely related to fibroids (middle vs. low: OR 0.56, 95%CI: 0.36, 0.85; high vs. low: OR 0.50, 95% CI: 0.32, 0.79; Ptrend = 0.002). In the hysterectomy-confirmed group, an inverse association was suggested between high-density lipoprotein cholesterol (HDL-C) and fibroids (OR 0.46, 95% CI: 0.25, 0.84, Ptrend = 0.014). Moreover, the effect of homocysteine concentration was not observed in this group. Conclusion(s) These findings suggest that women with uterine fibroids might have an increased risk of subclinical atherosclerosis.
Insulin resistance and its association to carotid subclinical atherosclerosis.  [PDF]
Abdel del Busto Mesa,Julio Oscar Cabrera-Rego,Julio C. Gandarilla Sarmientos,Juan Valiente Mustelier
Revista Cubana de Cardiología y Cirugía Cardiovascular , 2011,
Abstract: Objective To determine the association between insulin resistance and the presence ofcarotid subclinical atherosclerosis.Method We conducted a cross-sectional study that included 239 patients with suspicionof carbohydrates metabolism disorders, in collaboration between theEndocrinology National Institute and the Cardiology and Cardiovascular SurgeryInstitute. We included clinical (age, sex, personal antecedents of smokinghabit, high blood pressure and dislipidemia, systolic and diastolic bloodpressure), anthropometric (waist circumference and body mass index), biochemical(total cholesterol, C-HDL, C-LDL, triglycerides) and ultrasonographic(carotid intima-media thickness and carotid plaque presence) variables.Results Systolic (r=0,159, p=0,015) and diastolic blood pressure ( r=0,197,p=0,002), body mass index (r=0,314, p=0,000), waist circumference(r=0,380, p=0,000), triglycerides (r=0,143, p=0,028) and carotid intimamediathickness (r=0,145, p=0,027) showed a positive and significant correlationwith HOMA-IR. A significant increase in the presence of carotid intima-media thickness ≥75 percentile according to age, sex and race wasshown for the insulin resistance group (58,1 % vs 34,2 %, p=0,000 OR 2,92[2,00-4,25]).Conclusions Insulin resistance showed a positive and significant correlation with carotidintimae-media thickness.
Role of Surrogate Markers of Atherosclerosis in Clinical and Subclinical Thyroidism
Mehmet Gunduz,Ercan Gunduz,Fatih Kircelli,Nazan Okur,Mesut Ozkaya
International Journal of Endocrinology , 2012, DOI: 10.1155/2012/109797
Abstract: Background. Data on the relationship between homocysteine, plasminogen activator inhibitor 1, hs-CRP, fibrinogen, and carotid intima media thickness (CA-IMT) is plenty but contradicting and the majority of the studies investigated this issue in only specific thyroidism groups. The aim of this paper was to investigate these relations in patients with subclinical and clinical hypo- and hyperthyroidism. Methods. In this cross-sectional study, 16 patients from each thyroidism group and 20 healthy cases were enrolled. Fibrinogen levels and plasminogen activator inhibitor 1 (PAI-1) activity were assessed. CA-IMT was determined by gray-scale high-resolution color Doppler ultrasound. Results. Serum homocysteine levels were higher in hypothyroidic patients compared to the control (=0.003). Fibrinogen levels were higher in patients with subclinical hypothyroidism compared to other groups (<0.05). There was no difference between groups regarding PAI-1. Whereas total cholesterol, homocysteine, and LDL were correlated with CAIMT, hs-CRP, PAI-1, and fibrinogen were not. In the clinical hypothyroidism group, the correlation of homocysteine with CA-IMT was derived from the correlation between CA-IMT and homocysteine. Conclusions. Homocysteine and fibrinogen levels are higher in patients with clinical and subclinical hypothyroidism, respectively. Homocysteine level is associated with CA-IMTonly in patients with clinical hypothyroidism.
Subclinical atherosclerosis in northern and southern China: the Chinese paradox

Huang Jie,Wu Yang-Feng,Liu Xiao-Qing,Ding Ding,Zhao Lian-Cheng,Lu Bin,Li Xian,Wong Nathan D,Dustin Laurie D,Azen Stanley P,Detrano Robert C,

老年心脏病学杂志(英文版) , 2011,
Abstract: Background The incidence of coronary heart disease (CHD) is higher in Northern than that in Southern China, however differences in traditional CHD risk factors do not fully explain this. No study has examined the differences in subclinical atherosclerosis that may help explain the differences in incidence. This study examined these differences in subclinical atherosclerosis using coronary computed tomography (CT) for calcification between the Northern and Southern China. Methods We selected a random sample of participants in a large multi-center ongoing epidemiologic study for coronary calcium scanning in one northern city (North) (Beijing, n = 49) and in two southern cities (South) (Shanghai, n = 50, and Guangzhou, n = 50). Participants from the three field centers (mean age 67 years) underwent coronary risk factor evaluation and cardiac CT scanning for coronary calcium measurement using the Multi-Ethnic Study of Atherosclerosis scanning protocol. Results Adjusted log-transformed coronary artery calcium score in North China (Beijing) was 3.1±0.4 and in South China (Shanghai and Guangzhou) was 2.2±0.3 (P = 0.04). Mean calcium score for the northern city of Beijing was three times higher than that of the southern city of Guangzhou (P = 0.01) and 2.5 times higher than for the southern city of Shanghai (P = 0.03). Conclusions The extent of subclinical atherosclerosis is significantly higher in the northern city of Beijing than that in the two southern cities of Guangzhou and Shanghai, even after adjusting for standard cardiac risk factors. This finding suggests that standard risk factors do not fully explain north south differences in clinical CHD incidence.
Circulating Tryptase as a Marker for Subclinical Atherosclerosis in Obese Subjects  [PDF]
María Moreno, Josep Puig, Marta Serrano, José María Moreno-Navarrete, Francisco Ortega, Wifredo Ricart, Jose Manuel Fernandez-Real
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097014
Abstract: Introduction Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression. Tryptase is expressed highly in human atherosclerotic lesions and the inhibition of tryptase activity hampers its capacity to maintain cholesterol inside macrophague foam cells. We aimed to investigate the association between circulating tryptase levels and subclinical atherosclerosis through estimation of carotid intima-media thickness (c-IMT) as surrogate marker for increased cardiovascular risk in obese and non-obese subjects. Methods Circulating tryptase levels (ELISA) and metabolic parameters were analyzed in 228 subjects. Atherosclerosis (c-IMT>0.9 mm) was evaluated ultrasonographically. Results Significant positive associations were evident between circulating tryptase levels and BMI, fat mass, glycated haemoglobin, fasting insulin, HOMAIR, fasting triglycerides and ultrasensitive PCR (p<0.05 from linear-trend ANOVA). The positive association between tryptase levels and insulin resistance parameters, suggested a glucose homeostasis impairment in individuals with higher tryptase levels. The negative asociation between tryptase levels and HDL-cholesterol supports the proatherogenic role of this protease (p<0.0001). Circulating tryptase levels were strongly associated with c-IMT measurements (p<0.0001 from linear-trend ANOVA), and were higher in subjects with presence of carotid plaque (p<0.0001). Tryptase levels (beta = 0.015, p = 0.001) contributed independently to subclinical atherosclerosis variance after controlling for cardiovascular risk factors (BMI, blood pressure, LDL-cholesterol). Conclusions Circulating tryptase level is associated to obesity related parameters and has a close relation with various metabolic risk factors. Moreover, serum tryptase level was independently associated with c-IMT, suggesting its potential use as a surrogate marker for subclinical atherosclerosis in obese subjects.
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