Mario De Michele

Association of Obesity and Central Fat Distribution With Carotid Artery Wall Thickening in Middle-Aged Women

Background and Purpose— The association between obesity and atherosclerotic disease is controversial. In the present analysis, we evaluated whether common carotid intima-media thickness (IMT) and area, 2 markers of preclinical atherosclerosis, were increased in obese subjects. Methods— More than 5000 middle-aged women (n=5062; age, 30 to 69 years) living in the area of Naples, Southern Italy, were recruited for a prospective, currently ongoing study on the etiology of cardiovascular disease and cancer in the female population (the Progetto ATENA study). A subsample of 310 participants underwent high-resolution B-mode ultrasound examination, and the IMTs, intima-media areas, and lumen diameters of common carotid arteries were measured with a semiautomated computerized program. Subjects were divided into 3 groups on the basis of the recently published obesity guidelines for body mass index (BMI), a marker of general obesity, and tertiles of waist-to-hip ratio (WHR), a marker of regional obesity. Results— Women with a BMI ≥30 kg/m2 showed higher systolic and diastolic blood pressures, triglycerides, and fasting glucose and insulin, as well as lower high-density lipoprotein concentrations, than subjects with lower BMI. A gradual increase in common carotid IMT and intima-media area was observed when lean women (0.94±0.01 mm and 19.8±0.5 mm2, respectively) were compared with overweight (0.98±0.01 mm and 21.0±0.4 mm2) and obese (1.02±0.02 mm and 22.6±0.8 mm2, P <0.005 for linear trend) individuals. Similarly, women in the highest tertile of WHR (>0.85) had adverse risk factor profiles and thicker carotid intima-media complex than those in the first 2 tertiles (P <0.01 and P <0.05 for IMT and intima-media area, respectively). In multivariate analyses, BMI and WHR were significant predictors of carotid wall thickness, independently of other traditional and nontraditional cardiovascular risk factors (age, blood pressure, lipid abnormalities, fasting insulin). Conclusions— The present results indicate a graded and independent association between general and abdominal obesity—reflected by high BMI and WHR—and carotid artery wall thickening in a population of middle-aged women.

Arterial abnormalities in the offspring of patients with premature myocardial infarction.

BACKGROUND Findings from epidemiologic and autopsy studies suggest that the offspring of patients with premature coronary disease may be at increased risk for atherosclerosis. We undertook a study to determine whether changes in brachial-artery reactivity and thickness of the carotid intima and media, two markers of early atherosclerosis, are present in adolescents and young adults with a parental history of premature myocardial infarction. METHODS We enrolled 40 healthy young people whose parents had had premature myocardial infarction (48 percent male; mean [+/-SD] age, 19.0+/-5.2 years) and 40 control subjects who were matched with the first group according to age and sex. All the subjects underwent high-resolution B-mode ultrasound examinations for the measurement of the brachial-artery vasodilatory response after arterial occlusion (i.e., reactive hyperemia) and the intima-media thickness of the distal common carotid arteries. Lipid profiles, blood pressure while at rest, body-mass index, and smoking status were also determined. RESULTS As compared with the control subjects, the offspring of patients with premature myocardial infarction had lower flow-mediated reactivity of the brachial arteries (5.7+/-5.0 percent, vs. 10.2+/-6.6 percent in the control subjects; P=0.001) and greater mean intima-media thickness of the common carotid artery (0.49+/-0.08 mm, vs. 0.44+/-0.07 mm in the control subjects, P=0.004). In the subjects with a parental history of premature myocardial infarction, an inverse association was found between brachial-artery reactivity and carotid intima-media thickness (r=-0.46, P=0.003). In a conditional logistic-regression analysis, both brachial-artery reactivity and carotid intima-media thickness were significantly and independently correlated with a parental history of premature myocardial infarction. CONCLUSIONS Structural and functional changes are present at an early age in the arteries of persons with a parental history of premature myocardial infarction.

A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women.

Paraoxonase (PON) gene polymorphisms have been proposed as genetic markers of risk for cardiovascular disease (CVD). Sporadic results suggest they are correlated with intima-media thickness (IMT), an indicator of preclinical atherosclerotic disease. We have investigated whether polymorphisms PON 1 (M/L) 55, (Q/R) 192, PON 2 (S/C) 311 are related to site-specific carotid plaques in 310 middle-aged women. Subjects were also investigated for physical and biochemical parameters including oxidative markers to evaluate their effect on development of atherosclerotic plaques (IMT>1.2 mm) identified by high resolution B-mode ultrasound. We demonstrate that PON 1 (LL+ML) 55 is associated with plaques both at the bifurcation (OR=2.40; 95% CI 1.00-5.90) and at the common carotid artery (OR=2.75; 95% CI 1.01-7.50), and to the total number of plaques at any site (P<0.05). This polymorphism is an independent parameter with respect to other variables that are significantly associated with plaques, i.e. systolic blood pressure (OR=2.06; 95% CI 1.11-3.81) and oxidized low-density lipoprotein (LDL) antibodies (OR=1.96; 95% CI 1.05-3.69) in cases of common carotid plaques, and lipid peroxides (OR=1.86; 95% CI 1.00-3.50) in cases of bifurcation plaques. In conclusion, PON 1 (LL+ML) 55 but not PON 1 (Q/R) 192 or PON 2 (S/C) 311, appears to be an independent risk factor for increased carotid IMT in middle-aged women.

Myocardial global performance index as a predictor of in-hospital cardiac events in patients with first myocardial infarction

OBJECTIVE We sought to assess the ability of a Doppler index of global myocardial performance (MPI), measured at entry, to predict inhospital cardiac events in a series of patients with first acute myocardial infarction (AMI). METHODS A complete 2-dimensional and Doppler echocardiographic examination was performed within 24 hours of arrival at the coronary care department in 96 patients (81 men and 15 women; mean age 58 +/- 9 years) with first AMI. Patients were divided a posteriori into 2 groups according to their inhospital course: group 1 comprised 75 patients with an uneventful course and group 2 comprised 21 patients with a complicated inhospital course (death, heart failure, arrhythmias, or post-AMI angina). RESULTS There were no significant differences between the 2 groups with regard to history of hypertension, diabetes mellitus, hypercholesterolemia, site and size of infarction, and conventional parameters of diastolic function. However, patients with complications were significantly older (63 +/- 10 vs 55 +/- 8 years, P =.005) and had higher wall-motion score index and left ventricular end-systolic volume compared with patients without events (1.84 +/- 0.27 vs 1.52 +/- 0.30, P =.001; and 66 +/- 29 vs 47 +/- 21 mL, P =.009, respectively), whereas the ejection fraction was reduced (40 +/- 10% vs 52 +/- 10%, P =.0001). The mean value of the MPI was significantly higher in patients with cardiac events than in those without events (0.65 +/- 0.20 vs 0.43 +/- 0.16, P =.0001). A MPI >/= 0.47 showed a sensitivity of 90% and specificity of 68% for identifying patients with events, on the basis of the receiver operator curve. In a multivariable model, the MPI at admission remained independently predictive of inhospital cardiac events (odds ratio 15.6, 95% confidence interval 2.4-99, P =.003). CONCLUSION These data suggest that in the acute phase of AMI, the MPI measured at entry may be useful to predict which patients are at high risk for inhospital cardiac events.

Association between small dense LDL and early atherosclerosis in a sample of menopausal women

The association between small dense LDL particles and early atherosclerosis has been evaluated in a sample of middle-aged women. We analysed the relation between sd-LDL and common carotid intima media thickness in 228 menopausal women. LDL separation was performed by Lipoprint System: 7 LDL subfractions were obtained, mean LDL size and LDL score (% of sd-LDL) were calculated. Multivariate analysis showed a significant association between IMT (≥ 1.30 mm) and mean LDL size after controlling for age (OR 7.80; 95% CI 1.47-41.39; p = 0.016 for mean LDL particle size). IMT remained significantly related to mean LDL particle size after controlling for age and Apo B. In a subsequent multivariate analysis, after controlling for age, IMT (≥ 1.30 mm) was significantly related to LDL score (OR 12.15; 95% CI 1.29-114.36; p = 0.029 for LDL score), or age and Apo B (OR 10.13; 95% CI 1.07-95.71; p = 0.043 for LDL score). Our results suggest an association between sd-LDL and IMT, independently of age and Apo B. This data may indicate that sd-LDL are markers of early carotid atherosclerosis, and suggest that measurement of sd-LDL-C gives useful information in the risk assessment for atherosclerotic disease in menopausal women.

Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors

The current study sought to investigate the role of low-density lipoprotein receptor (LDLr) mutations in assessing the risk profile of familial hypercholesterolemia (FH) patients, independently of major cardiovascular risk factors. FH due to LDLr mutations is associated with premature atherosclerosis. The variable clinical severity of the disease in heterozygotes has been related to cholesterol levels and the coexistence of other cardiovascular risk factors, but the independent role of different LDLr mutations is still unclear. cDNA of LDL gene was sequenced in 102 patients with clinical features of heterozygous FH. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound imaging in all patients. Sixteen different mutations (5 never described) were found in 82 patients (49 families; mean age, 39 years; 53% women). One of the newly described mutations, the 2312-3 C-->A, was found in 24 patients (13 families). The mean of maximum thicknesses was significantly higher in the 2312-3 C-->A group than in patients with other LDLr mutations (P=.004 after adjustment for major cardiovascular risk factors). Similar results (P=.001) were obtained in the adjusted comparisons of probands only, and of the patients with similar baseline cholesterol (P=.002). This study indicates that the identification of an LDLr mutation can help to assess the risk profile of FH patients independently of the major cardiovascular risk factors.

Increased carotid intima–media thickness in healthy young subjects with a parental history of hypertension (parental hypertension and vascular health)

Preclinical abnormalities are detectable in young normotensive individuals with a positive parental history of hypertension (PHH).1 Increased carotid intima–media thickness (IMT) is considered an early and valuable predictor of atherosclerotic disease; however, information on the effect of PHH on potential vascular structural abnormalities in young normotensive healthy subjects is limited. The aim of this study was to evaluate the presence of carotid structural differences in normotensive young adults and children with and without PHH. The study population comprised 29 cases (healthy subjects with PHH, 45% males, mean (SD) age 23 (5) years) consecutively recruited among the offspring (age 11–30 years) of patients with essential hypertension who had been followed at the Hypertension Outpatient Clinic of the Department of Cardiology, Cardarelli Hospital of Naples, Italy. Parental hypertension was defined as a blood pressure of at least 140/90 mm Hg, measured on three different days in the supine position by sphygmomanometry. The control group consisted of 29 age-matched (+1 year) and sex-matched healthy subjects without PHH (parents not on antihypertensive drugs and blood pressure values <140/90 mm Hg at repeated examinations); they were offspring of patients admitted to the same hospital for a wide spectrum of acute illnesses unrelated to essential hypertension or hospital workers. To minimise the confounding effects of other known cardiovascular risk factors, we excluded individuals with a parental history of coronary, cerebral or peripheral arterial disease and/or diabetes mellitus. The …

Effect of high-density lipoprotein cholesterol levels on carotid artery geometry in a Mediterranean female population

Background Controversy remains on the relationship between high-density lipoprotein cholesterol (HDL-C) and atherosclerotic cerebrovascular disease. Methods Over 5000 women living in the area of Naples, Southern Italy, were recruited for a prospective study on the etiology of cardiovascular disease in the female population (the ‘Progetto ATENA’ study). A sample of 310 participants underwent high-resolution B-mode ultrasound examination and the intima-media thickness and diameters of common carotid artery were measured. In addition to routine biochemical tests, these women also had oxidation markers determined. Results Women in the upper HDL-C quartile (HDL-C>1.89 mmol/L) had significantly lower body mass index and waist-to-hip ratio values, and triglycerides concentrations when compared with women in the first three quartiles. A linear negative association was found between HDL-C and carotid intima-media thickness (1.07 ± 0.16 mm for the IV quartile versus 1.10 ± 0.20 mm for the III quartile, 1.15 ± 0.26 mm for the II quartile and 1.19 ± 0.23 mm for the I quartile; P< 0.01 by ANOVA). No difference was found between groups with regard to carotid diameters and oxidation markers. After adjustment for other cardiovascular risk factors, women in the highest quartile of HDL-C had a decreased risk of carotid intima-media thickening (OR 0.42, 95%CI 0.23-0.94). Conclusions In asymptomatic middle-aged women, HDL-C levels were independently and negatively associated with preclinical atherosclerotic changes of the carotid artery wall.

Radical-Trapping Activity, Blood Pressure, and Carotid Enlargement in Women

Abstract—The aim of this study was to evaluate the influence of traditional and nontraditional (oxidation markers) cardiovascular risk factors on the degree of adaptive response of the carotid wall to atherosclerotic disease, a process known as arterial enlargement. Five thousand sixty-two clinically healthy, middle-aged women living in the area of Naples participated in the “Progetto Atena” study; 310 of these women (potentially at higher atherosclerotic risk) underwent a high-resolution ultrasound scan of the carotid arteries. In addition to routine biochemical tests, these women had the determination of serum IgG antibody titer against oxidized LDL and measurement of thiobarbituric acid reactive substances and total radical-trapping activity potential of plasma. Age, systolic blood pressure, body mass index, and radical-trapping activity were all positively correlated with external and internal common carotid diameters, whereas triglycerides (positively) and HDL cholesterol (inversely) were related only to external diameter. After controlling for traditional cardiovascular risk factors, associations still persisted for age, systolic blood pressure, and plasma radical-trapping activity with external carotid diameters. However, in the quartile of women with highest total cholesterol (>7.38 mmol/L), the slope of the regression line between systolic blood pressure and external diameter was significantly flatter than in the three other quartiles (test for difference, P =0.014). Outward carotid enlargement is related to traditional and nontraditional risk factors and comes even before plaque development. Women with poor resistance to oxidative stress potentially have a difficulty to remodel their arteries in response to atherosclerotic stimuli.

Factors predicting coronary flow reserve impairment in patients evaluated for chest pain: an ultrasound study.

Objective To evaluate the impact of multiple cardiovascular risk factors on coronary flow reserve (CFR) in a large patient population with acute chest pain referred for coronary angiography. Methods Three hundred and ninety-four consecutive patients (mean age 59 ± 10 years) were enrolled in the study. Blood flow velocity was measured, using transthoracic echocardiography, in the middle-distal tract of the left anterior descending coronary artery (LAD) at rest and during infusion of high-dose dipyridamole in 6 min. CFR was calculated as the ratio of hyperaemic to basal peak diastolic flow velocity. All patients underwent coronary angiography within 48–72 h of CFR evaluation and a LAD stenosis was considered significant for lumen diameter narrowing ≥70%. Results Out of 394 patients, 11 patients (3%) were excluded because of inadequate quality of the spectral Doppler envelope. In the group of 269 patients with LAD stenosis <70%, CFR was significantly reduced in 64 patients with >2 risk factors compared to 205 patients with ≤2 risk factors (2.24 ± 0.48 vs. 2.52 ± 0.53, P < 0.005). On multiple logistic regression analysis, age, hypertension and diabetes mellitus were related to reduced CFR. In 114 patients with significant LAD disease, CFR was not reduced in patients with multiple cardiovascular risk factors. On multiple logistic regression analysis, the percentages of stenosis and diabetes mellitus were independent determinants of CFR. Conclusions In patients with acute chest pain, the occurrence of multiple cardiovascular risk factors adversely affected CFR in an additive manner, in absence of significant angiographic stenosis. Diabetes mellitus was a powerful coronary risk factor decreasing CFR both in patients with or without significant LAD disease.