Gabriella Iannuzzo

Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children

Childhood obesity is associated with an increased carotid intima-media thickness (IMT) and stiffness. Increased carotid wall thickening and rigidity are considered markers of subclinical atherosclerosis. The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of subclinical atherosclerosis in obese children. Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol. Twenty-six accepted and were randomly assigned to two different groups: the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet. Anthropometric measures and biochemical tests were performed in all children. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) and diameters of the common carotid artery. Considering both groups together, at 6 months, body mass index decreased from 28.3 ± 3.1 to 25.8 ± 3.3 kg/m2, systolic blood pressure from 119 ± 12 to 110 ± 11 mmHg (P< 0.001), diastolic blood pressure from 78 ± 8 to 74 ± 7 mmHg (P< 0.001), IMT from 0.48 ± 0.05 to 0.43 ± 0.07 mm (P< 0.001), stiffness from 3.57 ± 1.04 to 2.98 ± 0.94 mm (P = 0.002), and high-sensitivity C-reactive protein from 1.5 ± 0.9 (values log transformed) to 0.4 ± 1.1 (P < 0.001). No differences were detectable in fasting serum triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Insulin resistance (calculated by the HOmeostatic Model Assessment index [HOMA] score) significantly reduced only in the low-glycemic-index diet group (P < 0.04). In conclusion, this study confirms a benefit of hypocaloric diets on carotid IMT and stiffness in obese children and demonstrates, for the first time, an amelioration of insulin sensitivity in obese children after a low-glycemic index diet. These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile.

Effects of short-term reduction in serum cholesterol with simvastatin in patients with stable angina pectoris and mild to moderate hypercholesterolemia

To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.

Small dense low-density lipoprotein in familial combined hyperlipidemia: Independent of metabolic syndrome and related to history of cardiovascular events

INTRODUCTION It is unclear whether small dense low-density lipoprotein (sdLDL) are associated with familial combined hyperlipidemia (FCHL), independently of the metabolic syndrome (MS). It is also unclear whether sdLDL are related to history of cardiovascular (CVD) events in FCHL patients, independently of MS. PATIENTS AND METHODS Serum levels of sdLDL, expressed as percentage of total LDL cholesterol (LDL score), were determined in 137 probands with FCHL and in 133 normolipidemic, normotensive, normoglycemic healthy subjects. RESULTS In binary logistic regression age- and gender-adjusted LDL score values above the 90th and 95th percentiles of the values in the control group (10.23 and 13.11%, respectively) were found to be significant predictors of FCHL status, independently of MS diagnosis (p=0.007 and p<0.0001, respectively). Values of the LDL score above the 90th and the 95th percentile of the control group resulted to be significantly related to FCHL status, even after adjustment for the components of MS (p=0.006 and p=0.001, respectively). Among FCHL patients, values of the LDL score above 95th percentile of the values in the control group were found to be significantly related to personal and/or family history of CVD events, independently of age, gender, total cholesterol, apolipoprotein (apo) B, and MS status (p=0.016). The same significant relationship was found adjusting for all components of MS (p=0.034). CONCLUSIONS High concentrations of sdLDL are highly specific markers of FCHL, independently of concomitant MS. In FCHL patients high levels of sdLDL are related to history of CVD events, independently of MS, total cholesterol and apo B.

Carotid artery wall hypertrophy in children with metabolic syndrome

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6±2.6 years; range 6–14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl−1, fasting triglyceride concentration >100 mg dl−1, fasting high-density lipoprotein cholesterol concentration <50 mg dl−1 for females or <45 mg dl−1 for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima–media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima–media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83±1.86 mm2 [mean±s.d.] compared with the control group: 7.77±1.72 mm2, P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.

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.

Tumor necrosis factor-α is a marker of familial combined hyperlipidemia, independently of metabolic syndrome

It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.

Impaired endothelium-dependent vascular reactivity in patients with familial combined hyperlipidaemia

Background: Familial combined hyperlipidaemia (FCHL) is associated with a markedly increased risk of premature coronary artery disease. This study was designed to evaluate whether preclinical atherosclerotic functional abnormalities are detectable in the arteries of patients with FCHL. Methods: 60 subjects were recruited for the study: 30 probands of families with FCHL (mean (standard deviation (SD)) age 48 (10) years, 77% men), defined by fasting total plasma cholesterol or triglyceride concentration >250 mg/dl (>6.5 mmol/l cholesterol, >2.8 mmol/l triglyceride) and by the occurrence of multiple lipoprotein phenotypes within a family, and 30 age-matched and sex-matched healthy controls. All subjects underwent high-resolution B-mode ultrasound examination and the brachial arterial reactivity, a marker of endothelial function, was measured by a semiautomated computerised program. Lipid profile, resting blood pressure, body mass index (BMI), smoking status, insulin and homocysteine levels were also determined. Results: Compared with controls, patients with FCHL had significantly higher BMI, diastolic blood pressure and insulin levels. No difference was observed in baseline brachial diameter between the two groups (mean (SD) 3.45 (0.51) mm for FCHL v 3.60 (0.63) mm for controls; p = 0.17). In response to flow increase, the arteries of the controls dilated (mean (SD) 8.9% (4.9%), range 2.3–20.8%), whereas in the patients with FCHL, brachial arterial reactivity was significantly impaired (5.5% (2.5%), range 0–10.1%; p = 0.002). In multivariate linear regression analysis, apolipoprotein B and BMI were independent determinants of brachial artery response to reactive hyperaemia. Conclusions: The findings of our study suggest that vascular reactivity is impaired in the arteries of patients with FCHL.

Causative mutations and premature cardiovascular disease in patients with heterozygous familial hypercholesterolaemia

Background Familial hypercholesterolemia is a common autosomal dominant disease, caused by mutations leading to elevated low-density lipoprotein (LDL) cholesterol and, if untreated, to premature cardiovascular disease. Methods Patients (young adults with a family history of hypercholesterolaemia or premature cardiovascular disease) with LDL cholesterol concentration ≥4.9 mmol/l, after excluding Familial Combined Hyperlipidaemia, were evaluated for causative mutations, Dutch Lipid Clinic Network score calculation and non-invasive ultrasound examination of carotid arteries. Results Of the 263 patients, 210 were heterozygotes for LDL receptor (LDLR) mutations, four had APOB gene mutations, one PCSK9 gene mutation, while 48 had no evidence of mutations. Among 194 unrelated index cases 149 had mutations (77%). Among patients with LDLR mutations (n = 145), there were five compound heterozygotes, 75 patients with null mutations and 65 with missense mutations. As many as 178 patients underwent a follow-up and treatment (statin ± ezetimibe), achieving a mean reduction of 49% in LDL cholesterol, with 21% of patients reaching the LDL goal of 2.6 mmol/l. In a multivariate analysis, carotid plaques, at ultrasound examination, were associated with the presence of genetic mutation (p = 0.001), LDL cholesterol (p < 0.001), Dutch Lipid Clinic Network score (p < 0.001), independently of age, gender, smoking habits and systolic blood pressure. The presence of carotid plaque (p = 0.017), LDL cholesterol (p < 0.003), Dutch Lipid Clinic Network score (p < 0.001) were independently associated with premature cardiovascular disease. Conclusions We identified patients with causative mutations in 82% of the cases under study. In addition to LDL cholesterol and Dutch Lipid Clinic Network score, carotid plaques in ultrasound evaluation provide direct evidence of premature vascular disease and are associated with high risk for cardiovascular events.

Association between Lp (a) and atherosclerosis in menopausal women without metabolic syndrome

AIM The association between Lipoprotein (a) (Lp [a]) and common carotid intima media thickness (IMT) has been evaluated in 222 menopausal women. MATERIAL & METHODS Lp (a) and IMT were measured, carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. RESULTS Lp (a) was significantly lower in women with metabolic syndrome (MS). In a multivariate analysis Lp (a) showed the following odds ratio (OR; all p < 0.05) of having common carotid IMT (≥1.30 mm): 1.03, adjusted for age, low-density lipoprotein cholesterol (LDL) and waist circumference; 1.02, adjusted for age LDL, homeostatic assessment model (HOMA). In women without MS, after controlling for age, LDL and waist circumference, we found the following OR for increased IMT (≥1.30; OR: 1.03; for Lp [a]); 1.02 adjusted for age, LDL and HOMA (all p < 0.05). In women with MS these relationships were not statistically significant. CONCLUSION Lp (a) gives additional information in the risk assessment for atherosclerotic cardiovascular disease, especially in menopausal women without MS.

Association between body shape index and small dense LDL particles in a cohort of mediterranean women: findings from Progetto ATENA

Small dense LDL particles (sd-LDL) and body shape index (ABSI), were evaluated in 228 women, living in Naples, Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin, HOMA, Apo B, hs-CPR and sd-LDL were measured. LDL particle separation was performed by Lipoprint System: seven LDL subfractions were obtained and LDL score (% of sd-LDL particles) calculated. ABSI was calculated according to Krakauer’s formula: ABSI (m11/6 kg−2/3). The association between sd-LDL and ABSI was evaluated taking into account different adjustment models. Women with elevated levels of ABSI show the following OR of having high LDL score: 2.39, p = 0.002; unadjusted; 2.47, p = 0.002; adjusted for age; 2.13, p = 0.011; adjusted for age and Apo B; 1.93, p = 0.026; adjusted for age and Apo B and triglycerides. ABSI was associated with elevated LDL score independently of age, Systolic pressure, Apo B and triglycerides. Median of LDL diameter decreased among ABSI quartiles: quartile I: 271.5 nm, quartile II: 270.7 nm, quartile III 270.5 nm, quartile IV 269.4 nm; Kruskall Wallis Test: p = 0.016. These results are in line with the hypothesis that ABSI could be a marker of visceral abdominal associated to adverse metabolic changes including presence of elevated sd-LDL, a risk factor for premature cardiovascular disease.