Carotid Intima-media Thickness In Women Research Articles

Systolic blood pressure, mediated by arterial stiffness, is associated with carotid intima-media thickness in women but not men with type 2 diabetes mellitus

Background and Aims : There is a distinct sex disparity in cardiovascular diseases (CVD) among individuals with diabetes mellitus (DM). We aimed to study the impact of sex on cardiovascular risk factors, subclinical atherosclerosis and arterial stiffness in type 2 DM.

Association of hormonal and metabolic status with carotid intima-media thickness in women with polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Apolipoprotein-defined lipoprotein subclasses, serum apolipoproteins, and carotid intima-media thickness in T1D

Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and apolipoproteins predict vascular events in the general and type 2 diabetes populations, but data in T1D are limited. We examined associations of ADLS, serum apolipoproteins, and conventional lipids with carotid intima-media thickness (IMT) measured contemporaneously and 6 years later in 417 T1D participants [men: n = 269, age 42 ± 6 y (mean ± SD); women: n = 148, age 39 ± 8 y] in the Epidemiology of Diabetes Interventions and Complications study, the follow-up of the Diabetes Control and Complications Trial (DCCT). Date were analyzed by multiple linear regression stratified by sex, and adjusted for time-averaged hemoglobin A1C, diabetes duration, hypertension, BMI, albuminuria, DCCT randomization, smoking, statin treatment, and ultrasound devices. In cross-sectional analyses, lipoprotein B (Lp-B), Lp-B:C, Lp-B:E+Lp-B:C:E, Apo-A-II, Apo-B, Apo-C-III-HP (heparin precipitate; i.e., Apo-C-III in Apo-B-containing lipoproteins), and Apo-E were positively associated with common and/or internal carotid IMT in men, but only Apo-C-III (total) was (positively) associated with internal carotid IMT in women. In prospective analyses, Lp-B, Apo-B, and Apo-C-III-HP were positively associated with common and/or internal carotid IMT in men, while Lp-A1:AII and Apo-A1 were inversely associated with internal carotid IMT in women. The only significant prospective association between conventional lipids and IMT was between triacylglycerols and internal carotid IMT in men. ADLS and apolipoprotein concentrations may provide sex-specific biomarkers and suggest mechanisms for IMT in people with T1D.

Association of kallistatin with carotid intima-media thickness in women with polycystic ovary syndrome.

Kallistatin is a secreted protein that acts as a tissue kallikrein inhibitor. It has anti-inflammatory, antioxidant and vasoprotective properties. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with low-grade chronic inflammation and multiple risk factors for cardiovascular diseases. The aims of this study were to ascertain whether circulating kallistatin levels are altered in women with PCOS, and whether there is an association between kallistatin and carotid intima-media thickness (cIMT) as well as inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). This cross-sectional study included 75 women with PCOS and 75 age- and BMI-matched controls without PCOS. Circulating kallistatin and TNF-α levels were measured using ELISA. Metabolic and hormonal parameters, hs-CRP levels and cIMT were also determined. All subjects underwent the 2-hour oral glucose tolerance test (2-h OGTT). Circulating kallistatin levels were significantly elevated in women with PCOS compared to controls (6.31±2.09 vs. 4.79±2.26 ng/mL, P<0.001). Inflammatory markers hs-CRP and TNF-α were found to be elevated in women with PCOS. Kallistatin levels positively correlated with insulin, insulin resistance index (HOMA-IR), free androgen index, hs-CRP, TNF-α and cIMT in both PCOS and control groups. Kallistatin levels did not show correlation with BMI, blood pressure, fasting blood glucose, 2-h OGTT or HbA1c. Multiple linear regression analysis revealed that kallistatin is an independent predictor for cIMT (β=0.131, 95% CI: 0.114-0.150, P=0.019). Kallistatin levels may provide useful information regarding cardiovascular risk in women with PCOS.

Objective snoring time and carotid intima-media thickness in non-apneic female snorers.

Controversy persists about whether snoring can affect atherosclerotic changes in adjacent vessels, independently of obstructive sleep apnea and other cardiovascular risk factors. This study examined the independent association between snoring and carotid artery intima-media thickness (IMT) in non-apneic snorers and non-snorers. We studied 180 non-apneic snorers and non-snorers participating in a full-night home-based sleep study. Snoring sound was measured objectively by a microphone. Based on snoring time across the night, participants were classified as non-snorers (snoring time: 0%), mild snorers (1-25%) and moderate to heavy snorers (≥25%). We measured IMT on both common carotid arteries. The three groups were matched by age, body mass index, cholesterol, blood pressure and glucose levels, using weights from generalized boosted-propensity score models. Mean carotid IMT increased with increased snoring time across the night in women: non-snorers (0.707mm), mild (0.718mm) and moderate to heavy snorers (0.774mm), but not in men. Snoring during at least one-fourth of a night's sleep is associated independently with subclinical changes in carotid IMT in women only.

Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant.

Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant. In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: β=-0.0047, P=1.63 × 10(-4); men: β=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r(2) ≥ 0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0 × 10(-22)) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues. Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis.

Serum fibroblast growth factor 21 levels are related to subclinical atherosclerosis in patients with type 2 diabetes.

BackgroundFibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. However, the relationship between circulating FGF21 and subclinical atherosclerosis or atherosclerosis of other arteries such as the femoral and iliac artery remains unclear. In this study, we evaluated the association of serum FGF21 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.MethodsSerum FGF21 levels were detected by enzyme-linked immunosorbent assay in 212 newly diagnosed type 2 diabetic patients without clinical symptoms of atherosclerosis or cardiovascular diseases. IMT of the carotid, femoral, and iliac arteries were measured by high-resolution B-mode ultrasound to determine the presence of subclinical atherosclerosis, which was defined as having an IMT > 1.0 mm and/or plaque on one or more of the three arteries without any clinical manifestations. The relationship between serum FGF21 levels and subclinical atherosclerosis was analyzed.ResultsSerum FGF21 levels were significantly higher in patients with subclinical atherosclerosis compared to those without [261.3 (135.1–396.4) versus 144.9 (95.9–223.0) ng/L, P < 0.001]. These differences were also observed in both men and women with subclinical atherosclerosis compared to their respective groups without [men: 243.2 (107.6–337.0) versus 136.8 (83.6–212.8) ng/L, P = 0.048; women: 292.4 (174.2–419.9) versus 160.4 (115.3–258.5) ng/L, P = 0.001]. Moreover, serum FGF21 levels showed a significantly positive correlation with carotid IMT in women (r = 0.23, P = 0.018) and with iliac IMT in both genders (women: r = 0.27, P = 0.005; men: r = 0.22, P = 0.024). Multiple logistic regression analysis further showed that serum FGF21 was an independent impact factor for subclinical atherosclerosis in patients with type 2 diabetes.ConclusionsSerum FGF21 is elevated in newly diagnosed type 2 diabetes, and positively correlates with carotid and iliac lesions in patients with subclinical atherosclerosis, especially in women. High levels of FGF21 may be a compensatory reaction to offset atherosclerosis.

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Objectives This study aimed to assess vascular endothelial reactivity and carotid intima-media thickness in women with early- and late-onset preeclampsia, and with chronic hypertension. Methods A total of 28 women with uncomplicated pregnancies, 25 women with early-onset preeclampsia, 36 women with late-onset preeclampsia and 26 women with chronic hypertension were evaluated. We measured flow-mediated vasodilation in the brachial artery (FMD; marker of endothelial function), and intima-media thickness in the carotid artery (IMT; marker of atherogenesis) in women with early-onset preeclampsia during pregnancy and three months after delivery, and compared these parameters with those in normal, late-onset preeclampsia, and chronic hypertension. Results FMD was significantly lower during pregnancy in both preeclamptic and chronic hypertension groups, compared to the control group. FMD in late-onset preeclamptic group significantly increased and normalized 3 months after delivery. Although, FMD in the early-onset preeclamptic and chronic hypertension groups significantly increased 3 months after delivery, it showed still lower than control. IMT in early-onset preeclamptic and chronic hypertension groups, but not late-onset preeclamptic group, were significantly larger than that in control group. Conclusions These findings suggest that endothelial dysfunction is irreversible and atherosclerotic changes might be enhanced in women with early-onset preeclampsia and chronic hypertension. Disclosures T. Mori: None. K. Watanabe: None. A. Iwasaki: None. C. Kimura: None. A. Wakatsuki: None.

Correlation between Waist Circumference and Carotid Intima-Media Thickness in Women from Shanghai, China

ObjectiveTo evaluate whether waist circumference (WC) ≥85 cm is related to asymptomatic preclinical atherosclerosis in women from Shanghai, China. MethodsA total of 2365 females aged ≥20 years recruited from 4 communities underwent physical examination and carotid artery scanning. Their carotid intima-media thickness (C-IMT) was measured. ResultsThe C-IMT was significantly higher in overweight or obese women with their BMI ≥25.0 kg/m2 (P<0.01) and in those with their WC ≥85 cm than in those with their WC <85 cm (P<0.01). Spearman and partial correlation analysis showed that the C-IMT was significantly correlated with WC which was independent of menopausal status. The C-IMT significantly increased with the increasing WC and reached to a platform in about 85 cm. An increment tendency was found in the subgroup with its WC < 85 cm (P<0.01) while no significant tendency was found in the subgroup with its WC≥85 cm (P=0.07). Multiple stepwise regression analysis showed that the WC was an independent risk factor for C-IMT. In logistic regression model, the odd ratio of WC ≥80 cm, ≥80 cm and <85 cm and ≥85 cm for evaluating the risk of C-IMT elevation was 1.632, 1.501, and 1.878, respectively. ConclusionWC is significantly correlated with C-IMT in women from Shanghai, China, and WC≥85 cm may be used in identifying the risk of subclinical carotid atherosclerosis.

Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors

Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects. The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (r=0.32; P<0.001), but not in men (r=0.06; P=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (P=0.039), together with age (P<0.001) and hypertension (P=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted R(2)=35.8%; P<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (P=0.01). The present study is the first demonstration that elevated serum FGF21 levels are associated with carotid atherosclerosis in humans, independent of established risk factors including adverse lipid profiles and C-reactive protein. The role of FGF21 as a biomarker or therapeutic target of atherosclerotic diseases warrants further investigation.

The serum protein α2-Heremans-Schmid glycoprotein/fetuin-a concentration and carotid intima-media thickness in women with polycystic ovary syndrome

ObjectiveTo investigate fetuin-A concentrations and its association with metabolic and sonographic cardiovascular markers in women with polycystic ovary syndrome (PCOS) and healthy subjects. Study designThirty-five women with PCOS and 37 healthy control women were matched for body mass index (BMI) and age. Serum fetuin-A concentrations, and reproductive and adrenal hormones were measured, and insulin resistance and carotid intima media thickness (CIMT) were evaluated in both groups. The correlations between cardiovascular risk factors, CIMT and fetuin-A concentrations were tested. ResultsMean fetuin-A concentrations were significantly elevated in the PCOS group compared with control subjects (101.2ng/ml±33.55 vs. 82.5ng/ml±32.65, P=0.019). CIMT was also higher in women with PCOS than in control subjects (0.51±0.05mm vs. 0.44±0.05mm, P<0.01). Serum lipid parameters were correlated to serum fetuin-A concentrations in the PCOS group, but no correlation was found between fetuin-A and CIMT (rPCOS=0.244, pPCOS=0.158; rcontrol=−0.002, pcontrol=0.988). ConclusionIn this, the first study of fetuin-A concentrations in PCOS, the results showed that fetuin-A concentrations were increased in euglycemic patients with PCOS.

Carotid intima-media thickness in mainly non-obese women with polycystic ovary syndrome and age-matched controls

ObjectiveMetabolic disturbances are well-recognized clinical features of polycystic ovary syndrome (PCOS). Carotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD). CIMT in women with PCOS has been investigated in many studies, but there has been only one report in the Korean population. The aim of the present study was to compare the presence of subclinical atherosclerosis in young untreated Korean women with PCOS and age-matched controls, specifically by measuring their CIMT.MethodsCIMT was measured by one radiologist in 56 PCOS patients and 56 controls. To compare the CIMT according to PCOS phenotypes, women with PCOS were divided into two subgroups according to the presence of hyperandrogenism.ResultsAlthough PCOS patients were more obese and had higher blood pressure and insulin resistance index than the age-matched controls, the CIMT was not different between the two groups (0.49 ± 0.09 mm in PCOS patients vs. 0.50 ± 0.11 mm in controls, respectively, p = 0.562). When the CIMT in the control group was compared with hyperandrogenic and non-hyperandrogenic PCOS groups, also no significant differences were found.ConclusionDespite the significant differences in some vascular risk factors between women with PCOS and controls, PCOS patients did not have a significantly higher CIMT (even in the hyperandrogenic subgroups). Although our study did not show the increased risk of subclinical atherosclerosis in PCOS patients, the role of CIMT continues to be investigated considering the importance of screening and monitoring CVD risk factors in women with PCOS.

Gender differences in association between metabolic syndrome and carotid intima media thickness

BackgroundMetabolic syndrome (Mets) is a cluster of cardiovascular risk factors which can predicts cardiovascular disease (CVD). Carotid intima-media thickness (CIMT) is known as a surrogate measure of subclinical atherosclerosis and predictor of CVD. Although, it has shown the association between Mets and CIMT, this relation regarding sex differences is limited. We aimed to find out whether gender differences in this association.MethodsIn this cross-sectional study, we recorded height, weight, waist circumference (WC), blood pressure, and lipid profiles. We used Mets; defined based on NCEP ATP III definition, and traditional cardiovascular risk factors; age, body mass index (BMI), WC, hyperlipidemia, and hypertension, in multivariate regression models which including;. The CIMT measurement < 0.73 or ≥0.73 mm was considered as low- or high risk to CVD.ResultsOverall, 150 subjects were enrolled to study that their ages were 36-75 years. The 47.3% of them (71 subjects) had Mets. CIMT was increased in Mets group compared non-Mets group (P = 0.001). In logistic regression analysis, a significant association was found between Mets and CIMT in women, but not in men (p = 0.002, and p = 0.364, respectively). After adjustment to age, WC, BMI, hypertension and hyperlipidemia, this association was significant just in women (p = 0.011) independent of WC, BMI, hyperlipidemia and hypertension.ConclusionOur data showed that MetS is a stronger risk factor for subclinical atherosclerosis in women than in men. So, we suggest the assessment of CIMT along with definition Mets in middle-aged women could be lead to earlier detection of at risk individuals to CVD.

Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with cardiovascular disease (CVD) risk factors and metabolic disturbances. This systematic review and meta-analysis was conducted to determine whether carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is higher in women with PCOS compared with women without PCOS. Primary articles reporting the mean CIMT in women with PCOS and controls were identified using Ovid MEDLINE, EMBASE and PUBMED. We performed a random-effects meta-analysis and created forest plots of the mean difference in CIMT and conducted tests for heterogeneity and publication bias. Studies were grouped by quality, defined by reporting reproducibility of CIMT and averaging both common carotid arteries versus one side for CIMT. From the 36 eligible full-text studies, 8 studies were included in the systematic review and 19 studies were included in the meta-analysis (total n= 1123 women with PCOS, n= 923 controls). The summary mean difference in CIMT among women with PCOS compared with controls was 0.072 mm [95% confidence interval (CI) 0.040, 0.105, P < 0.0001] for highest quality studies, 0.084 mm (95% CI 0.042, 0.126, P = 0.0001) for good quality studies, 0.041 (95% CI -0.038, 0.120, P = 0.310) for fair-quality studies and 0.045 (95% CI -0.020, 0.111, P = 0.173) for lower quality studies. Larger studies with a well-defined PCOS population using rigorous methodology may be required to draw a more robust conclusion. However, these results suggest women with PCOS are at a greater risk of premature atherosclerosis, which emphasizes the importance of screening and monitoring CVD risk factors in women with PCOS.

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (P=0.30 and P=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (P for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.

Associations of Cholesterol and Glucose with Cardiovascular Dysfunction in Black Africans: The SABPA Study

The aim was to determine whether blood glucose or cholesterol is the more prominent contributor to cardiovascular dysfunction in 101 African men and 99 African women. We measured ambulatory daytime blood pressure (BP), carotid intima-media thickness (CIMT), and determined blood glucose and lipids in serum. High-density lipoprotein cholesterol (HDL) (p = 0.002) and HDL: total cholesterol (HDL:TC) (p ≤ 0.001) were significantly lower, while serum glucose (p ≤ 0.001) was significantly higher in men. In single, partial, and multiple regression analysis, BP correlated positively with blood glucose in men. Furthermore, CIMT (B = −0.50; p = 0.009) correlated negatively with HDL:TC in men. While in women CIMT (B = 0.346; p = 0.015) correlated positively with glucose. In conclusion, subclinical atherosclerosis is significantly related to an unfavorable HDL profile in men, whereas in women, this link is stronger with fasting glucose.

Job Stress and Carotid Intima‐media Thickness in Chinese Workers

Carotid intima-media thickness (CIMT) can be used as a surrogate marker for cardiovascular health, and job stress is a risk factor for cardiovascular disease. However, there have been a limited number of studies focusing on the association between job stress and CIMT. The goal of this study was to explore the association between job stress and CIMT in a Chinese working population. The study included 734 participants (508 males and 226 females) without coronary heart disease. Job stress was evaluated using the effort-reward imbalance (ERI) questionnaire at work. ERI is the ratio between efforts and rewards (weighted by number of items). High resolution carotid ultrasonographic studies were performed using a Sequoia 512 ultrasound system with an 8-13 MHz linear array transducer to assess CIMT. This study detected gender-specific associations between the indictors of the ERI model and increased CIMT among the study participants in China. This study demonstrated a robust association in women between the key indicators of ERI, effort, overcommitment and ERI, and increased CIMT (adjusted r(2)=0.258, p=0.001; adjusted r(2)=0.261; p<0.001; adjusted r(2)=0.274; p<0.001, respectively). Reward was inversely correlated with CIMT (adjusted r(2)=0.282, p<0.001), controlling for age, hypertension, diabetes mellitus, hyperlipidaemia and body mass index. For men, a similar pattern of associations was observed, but the associations were lost after adjustment for confounders. Our results show that effort, overcommitment and ERI may be associated with early atherosclerosis predicted by CIMT in women, and reward is inversely related to CIMT.

Metabolic syndrome and carotid intima media thickness in the Health 2000 Survey

Background and purpose Metabolic syndrome has been associated with increased carotid intima-media thickness (CIMT) and cardiovascular disease (CVD). The objective of this study was to examine metabolic syndrome as a determinant of CIMT in men and women and to compare the Framingham risk score (FRS) and metabolic syndrome as risk factors for increased carotid atherosclerosis. Methods The study population consisted of 1353 Finnish men and women aged 45 years and above who participated in Finnish population-based Health 2000 Survey. CIMT was used as a marker of subclinical atherosclerosis. The National Cholesterol Education Program Adult Treatment Panel III criterion was used to define the presence of metabolic syndrome. Results In multivariable models, metabolic syndrome was an independent determinant of CIMT in both sexes ( p ≤ 0.001 for both). When metabolic syndrome was included in the regression models along with its components, it was an independent determinant of CIMT in women but not in men. After dividing the population into risk categories according to FRS and the presence of metabolic syndrome, FRS predominantly determined CIMT regardless of the presence of metabolic syndrome in men. In women, however, CIMT was significantly higher in subjects with metabolic syndrome than in those without it, independently of the FRS. Conclusions Metabolic syndrome is an independent determinant of CIMT in both sexes. In women but not in men, metabolic syndrome is associated with CIMT independently of its components. Metabolic syndrome provides additional information on a person’s risk for early atherosclerosis beyond FRS in women but not in men.

Serum Adipocyte Fatty Acid-Binding Protein Levels Were Independently Associated With Carotid Atherosclerosis

Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an important player in atherosclerosis in animal models. However, the clinical relevance of these findings is still unknown. This study aims to examine the relationship between serum A-FABP level and carotid intima-media thickness (IMT), an indicator of atherosclerosis in humans. The study cohort included 479 Chinese subjects who underwent carotid IMT measurement. Serum A-FABP levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels positively correlated with carotid IMT in both men (r=0.211, P=0.001) and women (r=0.435, P<0.001). In women, but not in men, the presence of plaques was associated with significantly higher serum A-FABP levels (P<0.001 versus women without plaques). Stepwise multiple regression analysis showed that serum A-FABP level was independently associated with carotid IMT in women (P=0.034), together with age and hypertension (both P<0.001). A-FABP is an independent determinant of carotid atherosclerosis in Chinese women, but not in men. This gender difference may be attributed to the lower serum A-FABP levels in men, and the effect of other risk factors, such as smoking, among our male participants. Our results have provided clinical evidence supporting the role of A-FABP in the development of atherosclerosis.

Variation at the cholesteryl ester transfer protein gene in relation to plasma high density lipoproteins cholesterol levels and carotid intima-media thickness.

Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and polymorphisms regulating high density lipoproteins cholesterol (HDL-C) levels and the development of atherosclerosis, and found some polymorphisms (I405V and R451Q) to have minor effects. The purpose of this study was to investigate the combined effect of the several polymorphisms of the CETP gene so far found on HDL-C levels and carotid intima-media thickness (IMT), and, in addition, to study whether the recently found functional polymorphism in the promoter region of the CETP gene (C to A, - 629 relative to the first transcribed nucleotide) explains the previous associations due to linkage disequilibrium. The genotypes were determined in a population sample of 481 men and women. There were no significant differences in plasma CETP activity or carotid IMT between the genotypes of the promoter polymorphism. The women with the CC genotype of the promoter polymorphism had the lowest HDL-C levels (P < 0.001), but no such difference was seen in men. Detected polymorphisms of the CETP gene explained about 8% of the variation in HDL-C in women and about 7 and 10% of the variation in carotid IMT in women and men, respectively. The associations of the promoter, I405V and R451Q-A373P polymorphisms with HDL-C and carotid IMT seemed to be independent of each other. The associations with IMT were independent of total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT. The CETP gene locus was found to be polymorphic and its polymorphisms explained a reasonable proportion of the variation in the degree of carotid atherosclerosis.