Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia

Background and objectivesDefects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH.MethodsIn 436 Spanish FH patients (223 men and 213 women, age 44 ± 14 years) with known LDLR mutations, alleles were classified by standard criteria as null (n = 269), defective (n = 162), or undetermined (n = 5). LDLR defects were detected using a microarray (Lipochip^®) designed to uncover prevalent mutations in Spain and gene sequencing when no mutations were detected. Carotid IMT and plaque were assessed in FH patients and 268 healthy subjects.ResultsAll carotid measurements were increased in FH patients versus controls (p < 0.05), irrespective of genotype. After adjustment for gender and age, patients with null alleles compared with defective alleles had similar mean and maximum common carotid artery (CCA) IMT, but higher maximum IMT at any carotid segment, with median values (95% confidence interval) of 1.25 mm (1.19–1.31) and 1.11 mm (1.05–1.18), respectively. Multivariate analysis showed that null alleles were independently associated with maximum CCA-IMT (β = 0.09, p = 0.033) with an impact similar to that of gender (β = 0.10, p = 0.035).ConclusionsFH patients show advanced carotid atherosclerosis in relation to LDLR mutational class. The findings support the utility of genetic testing in FH beyond providing a secure diagnosis.     

Coronary heart disease risk equivalence in diabetes and arterial diseases characterized by endothelial function and endothelial progenitor cell

AimsPeripheral Arterial Disease (PAD), Carotid Artery Disease (CAD), and Type 2 Diabetes Mellitus (DM) were considered as “Coronary Heart Disease (CHD) risk equivalents”. Vascular endothelial dysfunction was recognized as an early event in the development of atherosclerosis. Involved in neovasculogenesis and maintenance of vascular homeostasis, endothelial progenitor cell (EPC) has been considered as a biological marker of cardiovascular disease. The purpose of this study was to assess the CHD risk equivalents concept by investigating the endothelial function and circulating EPC number in patients with CHD, PAD, CAD and T2DM.MethodsThere were four groups in the study: CHD (n = 19), AD [PAD and CAD (n = 17)], DM (n = 21) and healthy controls (HC, n = 20). PAD and CAD were assessed by ultrasonography. Coronal artery angiography was used to identify CHD. The diagnosis of T2DM was based on oral glucose tolerance test and medical history. Vascular endothelial function was assessed by flow-mediated brachial artery dilatation (FMD). Circulating EPC was quantified by flow cytometry.ResultsThe circulating EPC numbers in four groups were CHD, 973 ± 96; AD, 1048 ± 97; T2DM, 1210 ± 125; HC, 1649 ± 112 cells/ml. There were no significant differences in circulating EPC numbers between CHD and AD groups (P > 0.05). Compared with CHD or AD group, T2DM group was associated with a slight increase in circulating EPC numbers (P < 0.05). The results of FMD were almost similar to the circulating EPC numbers(CHD, 4.06 ± 0.54; AD, 3.90 ± 0.48; DM, 3.85 ± 0.57; HC, 5.52 ± 0.67%)except that there was no significant difference among the CHD, AD and T2DM groups (P > 0.05). Age, glycosylated hemoglobin, low density lipoprotein cholesterol, systolic blood pressure, body mass index (BMI) and medical history were the independent risk factors of circulating EPC number in all the patients (P < 0.05). Age, total cholesterol, BMI and medical history were the independent risk factors of FMD in all of the patients (P < 0.05).ConclusionsThe results of this study supported the equivalents hypothesis and revealed that “CHD risk equivalents” were characterized by the consistent physiological changes of blood vessels in angiogenesis, repairing ability and endothelial function.     

Prévalence et facteurs déterminants de l’épaisseur intima-media carotidienne élevée dans une population de 1203 hypertendus noirs africains

ObjectivesTo evaluate the prevalence and determinants of increased carotid intima-media thickness (IMT) in a population of black hypertensive patients and it influence of on the assessment of their overall cardiovascular risk.Patients and methodsThis was a 16-month, cross-sectional study conducted in the outpatient unit of the cardiology department of the Campus teaching hospital of Lome, and included 1203 hypertensive patients, both sexes, aged 35 years and more. Each patient benefited from a carotid IMT measure. Carotid IMT was increased if it was > 0.9 mm and the plaque was defined as a carotid IMT > 1.2 mm.ResultsThe mean age of our patients was 53.3 ± 10.4 years with a sex ratio of 1.6 in favor of women. The duration of hypertension was less than 5 years in 56.7% and hypertension was grade 1 in 47.7% of cases. The mean carotid IMT was 0.89 mm ± 0.20. The prevalence of the increased carotid IMT was 45.8% and that of an atheroma plaque was 15.8%. Carotid IMT was correlated with age (P ˂ 0.0001), duration of arterial hypertension (P = 0.01), history of stroke (P ˂ 0.0001), and presence of left ventricular hypertrophy to cardiac ultrasound (P = 0.01). The overall cardiovascular risk was modified after taking into account the carotid IMT. An increase in cardiovascular risk was observed in 30.5% of hypertensive patients.ConclusionIncreased carotid intima-media thickness is frequent in Togolese hypertension. The determining factors are age, duration of arterial hypertension, left ventricular hypertrophy and stroke. The systematic measurement of the carotid intima-media thickness would better evaluate the overall cardiovascular risk for our patients.     

High-sensitivity C-reactive protein (hs-CRP) in systemic lupus erythematosus patients without cardiac involvement; relation to disease activity,damage and intima-media thickness

Aim of the workTo assess the high sensitivity C-reactive protein (hs-CRP level) in systemic lupus erythematosus (SLE) patients without cardiac involvement and find its relation with clinical and laboratory findings, disease activity, damage index and intima-media thickness (IMT).Patients and methodsForty-five female SLE patients were recruited in the present study without any cardiac involvement. History taking, examination and laboratory investigations were performed for patients. Disease activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage by the Systemic Lupus International Collaborating Clinics (SLICC) index. Thirty age matched female healthy subjects were considered as a control group. hs-CRP was measured quantitatively by microplate immunoenzymometric assay and the IMT measured by ultrasonography.ResultsThe hs-CRP in the patients was significantly higher (4.84 ± 3.91 mg/l) compared to the control (1.74 ± 0.61 mg/l) (p < 0.001). The IMT in the patients was significantly increased (0.72 ± 0.37 mm) compared to the control (0.54 ± 0.15 mm) (p 0.004). There was no difference in the level of hs-CRP according to the presence or absence of clinical manifestations. However, it was significantly higher in those with positive DNA (5.71 ± 4.36 mg/L) compared to those with negative results (3.12 ± 1.97 mg/L) (p 0.009). There was a significant correlation of the hs-CRP level with the IMT (r 0.49, p 0.001) and SLEDAI (r 0.67, p < 0.001).ConclusionsThese findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of future cardiac events. Measuring hs-CRP may be useful as a marker of disease activity, increased IMT and subclinical atherosclerosis in SLE especially those with positive ds-DNA.     

Determinants of atherosclerosis in an Egyptian cohort of systemic sclerosis: Relation to disease activity and severity

BackgroundSystemic sclerosis (SSc) is a rare multi-system autoimmune disease characterized by vascular abnormalities with an increased prevalence of macrovascular disease.Aim of the workTo evaluate macro-vascular disease (atherosclerosis) in SSc patients and determine its relation to the disease activity and severity.Patients and methodsTwenty-five SSc patients and 20 matched controls were included. The modified Rodnan skin score (mRss) and disease severity by Medsger’s severity score were assessed. Carotid intima-media thickness (IMT) and flow mediated vasodilatation (FMD) of the brachial artery were measured. Traditional vascular risk factors were assessed by thorough history taking and laboratory investigations.ResultsThe age of the patients ranged from 15 to 60 years and they were 22 females and 3 males. 15 had limited and 10 diffuse cutaneous SSc. All SSc patients had an increased IMT (1.24 ± 0.29 mm) which was normal in the control subjects (0.77 ± 0.09 mm) (p < 0.0001). SSc patients had significantly lower HDL, thickened IMT and lower FMD than controls (p = 0.005, p < 0.0001 and p < 0.0001 respectively). The younger age of disease onset was significantly associated with more FMD impairment (r = −0.4, p = 0.04) and Medsger’s severity score (r = 0.5, p = 0.009). The mRss and Medsger’s severity score significantly correlated with the IMT (r = 0.84, p = 0.01 and r = 0.56, p = 0.003 respectively). A significant negative correlation was found between FMD and IMT (r = −0.77, p < 0.0001). Medsger’s severity score significantly correlated with FMD (r = −0.44, p = 0.02).ConclusionSSc is associated with an increased risk of atherosclerosis when compared to age and sex-matched controls. Determinants of this include; younger age of disease onset and more sever disease and low levels of HDL.     

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

ObjectiveMetabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS.MethodsEighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) ≥15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters.ResultsFifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS?OSA). Compared with MS?OSA patients, MS+OSA patients had higher levels of IMT (661 ± 117 vs. 767 ± 140 μm), PWV (9.6 ± 1.0 vs. 10.6 ± 1.6 m/s), and CD (6705 ± 744 vs. 7811 ± 862 μm) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R² = 0.42); AHI and systolic blood pressure (R² = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R² = 0.45), respectively. The R² of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively.ConclusionsOSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.     

Assessment of subclinical carotid atherosclerosis in patients with primary osteoarthritis: Correlation with disease severity and insulin resistance

Aim of the workTo assess the carotid artery intima–media thickness (IMT) as an index of subclinical atherosclerosis in patients with primary osteoarthritis (OA) and its correlation to severity and insulin resistance (IR).Patients and methodsThis study included 40 primary OA patients (28 with predominant knee OA and 12 with hip OA) and 15 age and sex matched controls. They were subjected to full medical history, thorough clinical examination and radiological assessment by plain X-rays of knee and hip joints scored according to the Kellgren–Lawrence grading. In patients and control, the IR was calculated by the homeostasis model assessment (HOMA) and carotid IMT measured by ultrasonography.ResultsThere was significant increased carotid IMT in OA patients (0.82 ± 0.12 mm) compared to controls (0.61 ± 0.02 mm) (p < 0.001) with cut-off value of 0.65 mm. There was significant higher HOMA in OA patients (2.55 ± 0.8) compared to controls (1.79 ± 0.44) (p < 0.001). OA patients with IMT > 0.65 mm (n = 34) had longer duration (9 ± 2.56y), higher Kellgren–Lawrence score (2.89 ± 0.45) and higher HOMA (3.8 ± 0.53) compared to those patients with IMT < 0.65 mm (n = 6) (3.41 ± 2.09 y, 2.01 ± 0.26 and 2.23 ± 0.32 respectively). Multi-regression analysis showed that disease duration, Kellgren–Lawrence Grading and HOMA are the best sensitive discriminators for patients having carotid intima >0.65 mm. (F ratio 36.54, p < 0.001).ConclusionOsteoarthritis patients have higher risk of subclinical atherosclerosis independent of traditional risk factors. The severity of OA may contribute to the progression of atherosclerotic disease. Measurement of insulin resistance in OA patients can identify those with higher risk of subclinical atherosclerosis and may help in their follow up and early intervention.     

The Impact of a Family History of Type 2 Diabetes on Insulin Secretion and Insulin Sensitivity in Individuals With Varying Glucose Tolerance

IntroductionThis study was performed to investigate the impact of a family history of type 2 diabetes (T2DM) on insulin resistance and beta-cell dysfunction in populations with varying glucose tolerance.MethodsAmong the total of 142 participants, 73 subjects with no family history of T2DM (FH?) included 42 with normal glucose tolerance (NGT/FH?) and 31 with impaired glucose tolerance (IGT/FH?); and 69 first-degree relatives of patients with T2DM (FH+) included 36 with NGT (NGT/FH+) and 33 with IGT (IGT/FH+). Insulin resistance was evaluated by Insulin Sensitivity Index (ISI) based on the euglycemic hyperinsulinemic clamp. Islet beta-cell function was assessed by disposition index (DI) for the acute insulin response to glucose (AIRg) using intravenous glucose tolerance test. Metabolic data were compared between groups after adjustment for age, sex, body mass index and waist-to-hip ratio.ResultsThe NGT/FH+ group showed lower level of ISI (P = 0.023) than the NGT/FH? group, whereas no difference was found in AIRg or DI between these 2 subgroups. In the FH? individuals, both ISI and DI of the IGT/FH? group decreased compared with the NGT/FH? group (both P < 0.05). In the FH+ individuals, no difference was found in ISI between the IGT/FH+ and NGT/FH+ groups, whereas the IGT/FH+ group had a lower level of AIRg and DI than the NGT/FH+ group (both P < 0.0001).ConclusionsThis study showed that the pathophysiological changes were different between individuals with and without a family history of T2DM during the glucose tolerance aggravation.     

Uric acid and high sensitive C-reactive protein are associated with subclinical thoracic aortic atherosclerosis

Background and purposeThe detection of atherosclerotic lesions in the aorta by transesophageal echocardiography (TEE) is a marker of diffuse atherosclerotic disease. Hyperuricemia is a well-recognized risk factor for cardiovascular diseases. However, no data are available concerning the relationship between serum uric acid (UA) and subclinical thoracic aortic atherosclerosis. We aimed to investigate the association between thoracic aortic atherosclerosis and serum UA level.MethodsWe studied 181 patients (mean age 46.3 ± 8 years) who underwent TEE for various indications. Four different grades were determined according to intima–media thickness (IMT) of thoracic aorta. UA and other biochemical markers were measured with an automated chemistry analyzer.ResultsTEE evaluation characterized thoracic aortic intimal morphology as Grade 1 in 69 patients, Grade 2 in 52 patients, Grade 3 in 31 patients, and Grade 4 in 29 patients. The highest UA level was observed in patients with Grade 4 IMT when compared with Grade 1 and 2 IMT groups (p < 0.001 and p = 0.014, respectively). UA levels in patients with Grade 3 and Grade 2 IMT were also higher than patients with Grade 1 IMT group (p < 0.001, for all). In multiple linear regression analysis, IMT was independently associated with UA level (β = 0.350, p < 0.001), age (β = 0.219, p = 0.001), total cholesterol (β = ?0.212, p = 0.031), low-density lipoprotein cholesterol (β = 0.350, p = 0.001), and high sensitivity C-reactive protein (hsCRP) levels (β = 0.148, p = 0.014).ConclusionUric acid and hsCRP levels are independently and positively associated with subclinical thoracic atherosclerosis.     

Cardiovascular risk factors and subclinical atherosclerosis among Nunavik Inuit

ObjectiveTo evaluate subclinical atherosclerosis in Nunavik Inuit and its correlation to traditional cardiovascular disease risk factor.MethodThe intima–media thickness (IMT) of 12 segments of the carotid arteries (IMT_{12_seg}) free of plaque were assessed in randomly selected 40 years old and older Inuit from. Clinical assessment was performed which included fasting plasma glucose, fasting insulin, systemic blood pressure, body mass index, smoking, circulating blood lipids and oral glucose tolerance test. In addition, documented presence of ischemic heart disease (IHD), stroke, diabetes mellitus, hypertension and dyslipidemia were determined from medical files.ResultsThe average age of the 287 participants was 51.2 ± 0.6 years (56.8% women). Mean IMT_{12_seg} was 0.80 ± 0.17 mm (range: 0.55–1.47 mm). Compared with disease free Inuit, individuals with history of stroke showed greater carotid internal IMT (0.68 ± 0.01 mm vs. 0.96 ± 0.15 mm respectively; p < 0.005) but no difference was observed for IHD. Hypertensive and dyslipidemic Inuit had higher IMT_{12_seg} compared to risk factor free individuals but no difference was observed in diabetics. None of the clinical assessments were associated with IMT_{12_seg}. In a multivariate backward elimination model, only age, gender, and medically documented history of hypertension were found to be predictors of IMT_{12_seg} (adjusted r-square of 0.54; p < 0.0001).ConclusionCompared with disease free Nunavik Inuit, subclinical signs of atherosclerosis determined by IMT was higher in individual diagnosed with stroke. Independent predictors of IMT_{12_seg} in our group were age, gender and history of hypertension. No other traditional risk factors imparted IMT.     

Gender-specific association between carotid intima-media thickness and Reynolds risk score

Background and aimAppropriate assessment and prevention of cardiovascular (CV) disease is one of the most important medical tasks worldwide. Carotid artery intima-media thickness (CIMT) is a marker of atherosclerosis, which has been associated with CV events. We examined the associations of a panel of different clinical, laboratory, and ultrasound variables simultaneously and individually with CIMT; to reveal the presence of additional surrogate markers of atherosclerosis to CIMT.Subjects and methods407 Consecutive non-diabetic individuals (220 men) who underwent comprehensive CV evaluation were included. The maximum IMT of the common and internal carotid artery on the right and left side of the neck were recorded by ultrasonography, and CIMT was calculated as the average of the four measurements. Ten-year Reynolds risk score (RRS) for CV events was calculated online for men and women. CAVI was measured using a VaSera vascular screening system, and the averages of the right and left CAVI were used for analysis after being adjusted for age.ResultsUnivariate linear regression models were constructed to test the association of each of the independent variables with the log-transformed CIMT values [Ln (average CIMT) + 2] separately for men and women. Only the variables with non-adjusted p ? 0.1 were included in the final multivariately-adjusted stepwise linear regression model. After multivariate adjustment, only two variables were significantly and independently associated with log-transformed CIMT values in males (the log-transformed Reynolds risk score and the average age-matched CAVI) and females (the average age-matched CAVI and systolic blood pressure).ConclusionRRS could be a candidate marker of atherosclerosis in men but not in women, while age-adjusted CAVI could be considered a marker of atherosclerosis in both genders.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

Background & AimsRecent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.MethodsWe recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45 years old (median age 31.6 ± 8.1 years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx).ResultsTotal cholesterol (P < 0.013) and LDL-cholesterol (P < 0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P < 0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P < 0.006 and P < 0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P < 0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis.ConclusionsYoung IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.     

Polymorphism in the IL10 promoter region and early markers of atherosclerosis: The Cardiovascular Risk in Young Finns Study

ObjectiveInflammatory factors modify the risk of coronary heart disease. Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene (IL10) is known to be associated with the variation of IL-10 production. We investigated whether single-base exchange polymorphisms ?1082 G>A (rs1800896), ?819 C>T (rs1800871) and ?592 C>A (rs1800872) at IL10 gene are associated with risk factors and early markers of atherosclerosis in young subjects.Methods and results: As a part of the Cardiovascular Risk in Young Finns Study, we determined carotid artery compliance (CAC), stiffness index (SI) and Young's elastic modulus (YEM), intima media thickness (IMT), IL10 genotype and atherosclerosis risk parameters for 2260 subjects aged 24–39 years. In male subjects CAC was lower in carriers of IL-10 high- to intermediate-producer haplotype ?1082 G; ?819 C; ?592 C (GCC+, 1.96 ± 0.67) than in noncarriers (GCC?, 2.10 ± 0.62, %/10 mmHg, mean ± SD, p = 0.0010). An inverse association was observed in SI (GCC+, 5.76 ± 2.12 and GCC?, 5.26 ± 1.46, p = 0.0034) and YEM (GCC+, 347 ± 165 and GCC?, 305 ± 110, mm Hg · mm, p = 0.0005). Associations remained significant when adjusted to age, BMI, smoking and serum lipids as well as fasting glucose and insulin levels. The genetic effect size for these parameters was not significant in women.Conclusions: IL10 promoter region high- to intermediate-producer haplotype GCC associates with decreased arterial elasticity in men. These results are in disconcordance with the supposed antiatheromatous properties of IL-10.     

MCP-1 gene A-2518G polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes

AimsCardiovascular diseases are the major cause of mortality in patients with diabetes mellitus. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in cardiovascular diseases. The objective of this study was to evaluate the relation between the genotypes of the MCP-1 A-2518G polymorphism and the development of carotid atherosclerosis in patients with type 2 diabetes.MethodsThe subjects were 303 unrelated patients who were diagnosed with type 2 diabetes mellitus. To evaluate macroangiopathy, we measured carotid artery intima-media thickness (IMT) by ultrasonography. The MCP-1 A-2518G polymorphism was determined by TaqMan PCR method.ResultsIMT in patients with the MCP-1 −2518 AG or GG genotype was significantly greater than the AA-genotype (P = 0.007). Simple regression analysis showed that age, systolic blood pressure, LDL-cholesterol, the MCP-1 −2518 AG + GG polymorphism, and HbA1c level were correlated with IMT (P < 0.0001, <0.0001, 0.006, 0.007, 0.025, respectively). In multiple regression analysis, the MCP-1 −2518 AG + GG polymorphism was the third strongest independent determinant of IMT in patients with type 2 diabetes (P = 0.021), subsequent to age and systolic blood pressure.ConclusionAssessment of the MCP-1 A-2518G polymorphism would be useful in identifying the risk of developing carotid atherosclerosis in patients with type 2 diabetes.     

Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial

Background/PurposeFamily history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Materials/MethodsBaseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%).ResultsThese patients were younger (median 56.7 vs. 62.1 years, P < 0.0001) and more often current smokers (52.4% vs. 43.5%, P < 0.0001), had more dyslipidemia (47.7% vs. 41.1%, P = 0.0003), less diabetes mellitus (14.1% vs. 17.5%, P = 0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P = 0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P = 0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P = 0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P = 0.046 and 4.8% vs. 7.7%, P = 0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI] = 1.00 [0.70, 1.44], P = 0.98).ConclusionsA family history of premature CAD is not an independent predictor of higher mortality.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study

ObjectivesTo investigate the extent of subclinical atherosclerosis in asymptomatic familial hypercholesterolemia (FH) patients using non-invasive images techniques.Patients, methods and resultsThe atherosclerotic burden of 36 molecularly defined FH patients (18 males, 45.7 ± 10.9 years) without evidence of cardiovascular disease receiving lipid-lowering treatment and 19 (47.8 ± 11.3 years) controls was investigated. Descending thoracic aorta magnetic resonance imaging (MRI) was performed in a 1.5 T equipment with T1 and T2 sequences to characterize atherosclerotic plaques and to measure aortic wall volumen. Carotid intima-media thickness (cIMT) and presence of plaques were measured using B-mode carotid ultrasound.Mean aortic wall volumen, cIMT and atherosclerotic plaques in aorta were significantly higher in FH cases (P < 0.001). A significant correlation between aortic wall volume and cIMT was observed (P < 0.01). Aortic MRI detected plaques in 94% and carotid ultrasound in 14% of cases. Lipid-rich plaques were observed only in FH cases (33%) and were associated with family history of premature coronary artery disease (P < 0.05).ConclusionsAsymptomatic middle-aged FH patients have significantly higher atherosclerotic burden than controls. cIMT has shown a significant correlation with aortic wall volume and MRI allowed the detection of lipid-rich plaques in FH subjects that were associated with family history of premature coronary artery disease.     

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

ObjectiveTo evaluate possible subclinical atherosclerosis using biomarkers and ultrasound-guided methods in a group of adolescents having fathers with premature atherosclerosis.MethodsThirty-three subjects whose fathers had a history of premature coronary artery disease and 30 counterparts whose fathers had no history of coronary artery disease were included in the study.ResultsThe homocysteine levels, high-sensitivity C-reactive protein levels, and cardiac chamber sizes and functions did not differ between the two groups. The carotid stiffness index β (CSI), the intima-media thickness (CIMT) and aortic pulse wave velocity (PWV) values were higher in the group with a family history of coronary artery disease, but only the difference in the CSI was statistically significant (CSI 3.07 ± 1.33 vs 3.88 ± 1.25, P = 0.015; CIMT 0.53 ± 0.09 mm vs 0.57 ± 0.08 mm, P = 0.068; PWV 3.49 ± 0.53 m/s vs 3.78 ± 0.63 m/s, P = 0.053).ConclusionAmong several markers of subclinical atherosclerosis, the CSI was significantly higher in adolescents who had a family history of premature atherosclerosis. The small sample size, the multifactorial nature of atherosclerosis or the insufficient power of these methods may explain these results.     

Association of Hepatitis C Virus Seropositivity With Inflammatory Markers and Heart Failure in Persons With Coronary Heart Disease: Data From the Heart and Soul Study

BackgroundHow hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown.Methods and ResultsAmong a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-α) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P < .01), but higher levels of TNF-α (7.1 vs. 4.8; P < .01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000 p-y (P < .01), CV events 62 vs. 40 (P = .13), and heart failure 76 vs. 29 (P < .01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR = 2.13; 95% CI: 1.19–3.80).ConclusionsIn this cohort with CHD, HCV seropositive participants had higher rates of death, CV events, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.