Overall dietary variety and adherence to the Mediterranean diet show additive protective effects against coronary heart disease.

BACKGROUND AND AIM: Along with the increasing evidence of the cardioprotective effects of the Mediterranean Diet (MD), the scientific interest and advocacy of dietary variety as a potentially healthy eating habit gradually faded, until its complete oblivion in the latest European cardiovascular prevention guidelines. Our study aims to investigate whether dietary variety adds to the "Mediterranean-ness" of the diet in protecting against coronary heart disease (CHD). METHODS AND RESULTS: In this case-control Italian study, data on eating habits were collected from 178 patients with CHD and 155 healthy controls, primarily males, frequency matched for age and gender, using the Food Frequency Questionnaire (FFQ) of the European Prospective Investigation into Cancer and Nutrition. Adherence to MD was estimated from FFQ by the Mediterranean Diet Score (MDS), an index developed by Trichopoulou (2003) ranging from 0 to 9, with higher scores indicating a stricter adherence. Overall dietary variety was computed from FFQ as a count of single food items consumed at least once a month. Associations between MDS or overall dietary variety and coronary status were evaluated by logistic regression models adjusted for BMI, physical activity, smoking, education, and caloric intake; the Odds Ratio (OR) for CHD for each 1.5-point increase in MDS was 0.76 [IC 95% 0.59; 0.98], whereas the OR for CHD for each 15-item increase in dietary variety was 0.62 [IC 95% 0.46; 0.84]. Remarkably, adherence to MD and overall dietary variety were independently associated with a significantly reduced chance of CHD. CONCLUSION: Dietary Mediterranean-ness and overall dietary variety exhibit additive cardioprotective effects.

Traditional Risk Factors are Causally Related to Carotid Intima-Media Thickness Progression: Inferences from Observational Cohort Studies and Interventional Trials.

In the present review, associations between traditional vascular risk factors (VRFs) and carotid intimamedial thickness progression (C-IMTp) as well as the effects of therapies for VRFs control on C-IMTp were appraised to infer causality between each VRF and C-IMTp. Cohort studies indicate that smoking, binge drinking, fatness, diabetes, hypertension and hypercholesterolemia are associated with accelerated C-IMTp. An exception is physical activity, with mixed data. Interventions for the control of obesity, diabetes, hypertension and hypercholesterolemia decelerate C-IMTp. Conversely, scarce information is available regarding the effect of smoking cessation, stop of excessive alcohol intake and management of the metabolic syndrome. Altogether, these data support a causative role of several traditional VRFs on C-IMTp. Shortcomings in study design and/or ultrasonographic protocols may account for most negative studies, which underlines the importance of careful consideration of methodological aspects in investigations using C-IMTp as the outcome.

Trials in "True" Dyslipidemic Patients Are Urged to Reconsider Comprehensive Lipid Management as a Means to Reduce Residual Cardiovascular Risk.

Randomized cardiovascular trials aimed to reduce the excessive residual risk in high-risk patients through a more aggressive low-density lipoprotein-cholesterol control or targeting triglycerides or high-density lipoprotein-cholesterol levels have shown a null or, at best, limited incremental benefit. In some cases, the treatment produced meaningful effects only in study subgroups. As a consequence, some compounds were withdrawn (e.g., nicotinic acid derivatives and cholesteryl ester transfer protein inhibitors), whereas others (fibrates) are utilized with reluctance due to the low level of evidence-based data. By reviewing these trials analytically, we identified a common feature that might explain their meager results: most of them involved patients generically at high cardiovascular risk with normal or near normal lipid levels and not patients with "true" dyslipidemia, who would receive the treatment if it were part of usual care. These observations may warrant re-examining a central criterion of pragmatism, eligibility, in the outline of forthcoming cardiovascular trials with novel lipid-modifying drugs.

Assessment of oxidative stress in coronary artery bypass surgery: comparison between the global index OXY-SCORE and individual biomarkers.

The performances of the OXY-SCORE, a summary index of oxidative stress, and of its individual components (plasma malondialdehyde (MDA), oxidized and reduced glutathione, individual antioxidant capacity, alpha- and gamma-tocopherol and urinary isoprostanes) were assessed in 47 patients undergoing coronary surgery, randomly assigned to cardiopulmonary bypass (CPB) or off-pump procedure (OPCAB) associated with less oxidative stress. The ability of the OXY-SCORE to classify correctly the patients was high (area under the ROC curve 0.90). Only free MDA showed a similar performance, but it was insensitive to the minor variations of the oxidative balance in the OPCAB group.

Effects of timing and extent of smoking, type of cigarettes, and concomitant risk factors on the association between smoking and subclinical atherosclerosis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the effects of timing and extent of smoking, type of cigarettes, and concomitant vascular risk factors (VRFs) on the association between smoking and carotid intima-media thickness (C-IMT) in a lipid clinic population. METHODS: 1804 patients (869 men, age 21 to 85 year) participated in the study. Smoking habits were recorded and C-IMTs were measured by B-mode ultrasound. The associations of C-IMT with smoking status (never, former, and current) and with the cigarettes' content of tar, nicotine, and carbon monoxide (alone or combined to define "light" or "regular" cigarettes) as well as the interactions between smoking status, gender, and VRFs were evaluated before and after adjustment for confounders. RESULTS: C-IMT was highest in current smokers, lower in former, and lowest in never smokers. C-IMT of former and current smokers differed only after data adjustment for variables describing the extent and timing of smoking exposure. C-IMT was positively related to the number of pack-years (number of cigarettes smoked per day [cigarettes/d] multiplied by number of years smoked/20) in both former and current smokers. There were no differences in C-IMT between smokers of cigarettes with high or low nicotine, tar, or carbon monoxide content. Both diabetes and hypertension interacted positively with smoking in determining C-IMTs. CONCLUSIONS: In the present cross-sectional observational investigation, carried out in a cohort of patients attending a lipid clinic, consumption of light cigarettes does not reduce the atherogenic effect of smoking on C-IMT. The number of pack-years, cigarettes/d, and years of smoking are relevant covariates in evaluating the effects of smoking on vascular health. The presence of diabetes or hypertension strengthens the association between smoking and cardiovascular risk.

Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient.

INTRODUCTION: Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery disease (CAD). This review attempts to identify which patients, among those with ED and no cardiovascular (CV) disease, should be screened for early, subclinical CAD, which coronary targets should be investigated, and which tests should be used. MATERIALS AND METHODS: A comprehensive evaluation of available published data included analysis of published full-length papers that were identified with Medline and Cancerlit from January 1988 to January 2006. RESULTS: Initial screening of patients with ED may adopt risk assessment office-based approaches to score patients into low, intermediate, or high risk of future cardiovascular events. Attention should be drawn to patients at intermediate risk. Targets for the assessment of subclinical CAD in this subset of patients should include both obstructive (flow-limiting) and nonobstructive (non-flow-limiting) CAD. Some tests address obstructive atherosclerosis by directly assessing coronary flow reserve (i.e., standard exercise stress test, rest/stress myocardial scintigraphy or echocardiography). Other tests are general measures of atherosclerosis burden (not necessarily obstructive) either in the coronary circulation (i.e., coronary calcium score by electron-beam computed tomography), or in extracoronary vessels (i.e., ankle brachial index, carotid intima-media thickness by B-mode ultrasound) as surrogate markers of CAD. Although a systematic use of these measures of nonobstructive atherosclerosis burden has not yet been recommended in the guidelines for coronary risk assessment, their use is progressively being extended from the research area to clinical practice. CONCLUSIONS: ED is definitely a vascular disorder and all men with ED should be considered at risk of CV disease until proven otherwise. Available risk assessment charts should be used to stratify (low, intermediate, and high) the coronary risk score in each patient with ED.

Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent.

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in the gene coding for the low density lipoprotein receptor (LDL-R). It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to premature coronary artery disease. We studied the probands of five FH Sicilian families with 'definite' FH and one proband of Paraguayan descent with homozygous FH who has been treated with an effective living-donor liver transplantation. In order to seek the molecular defect in these six families, we used direct sequencing to define the molecular defects of the LDL-R gene responsible for the disease. We described three novel missense mutations (C100Y, C183Y and G440C), two frameshift mutations (g.1162delC in exon 8 and g.2051delC in exon 14) and one mutation (g.2390-1Gright curved arrow A) at splicing acceptor consensus sequences located in intron 16 of the LDL-R gene; the analysis of cDNA of this splicing mutation showed the activation of a cryptic splice site in intron 16 and the binding studies showed a reduction in internalisation of LDL-DIL in the proband's cultured fibroblasts. Moreover, a g.2051delC in exon 14 was identified in the proband of Paraguayan ancestry with clinical features of homozygous FH. The mutation identified in the South American patient represents the first description of a variant in South American patients other than Brazilian FH patients. The 5 mutations identified in the Sicilian patients confirm the heterogeneity of LDL-R gene mutations in Sicily.

Lipoproteína (a) y riesgo de enfermedad coronaria en hombres hipercolesterolémicos / Lipoprotein (a) as a risk factor for coronary heart disease in hypercholesterolemic men

La Lp(a) es una partícula con capacidad aterogénica que ha sido indicada, con resultados contradictorios, como factor de riesgo coronario. En el presente estudio fueron incluídos 121 hombres con hiperlipidemia severa (valores de colesterol > 30 mg/dl), de los cuales 66 tuvieron evidencias de enfermedad coronaria, y un grupo control de 55 hombres. Se realizó un análisis multivariado con regresión logística, incluyendo las siguientes variables: edad, colesterol, HDL-colesterol, triglicéridos, Lp(a). Los resultados del presente estudio sugieren que la Lp(a) es un parámetro de riesgo independiente en hombres con hiperlipidemia severa, por lo cual su determinación permitiría seleccionar entre los sujetos hiperlipidémicos un subgrupo con mayor riesgo de enfermedad coronaria

Reproducibilidad de la cuantificacion de la sensibilidad a la accion insulinica con el modelo minimo y comparacion con un test de tolerancia a bajas dosis de insulina / Repeatibility of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test

La hiperinsulinemia y la insulino-resistencia son disturbios metabólicos associados a obesidad central, hipertensión arterial, hipertrigliceridemia, sindrome polimetabólico, intolerancia a la glucosa y enfermedad aterosclerótica. La evaluación de los cambios en la sensibilidad a la acción insulínica in vivo (SAI in vivo) inducidos por intervenciones higiénico-dietéticas o farmacológicas requieren una técnica de adecuada reproducibilidad. En el presente estudio fue evaluada la reproducibilidad intra-individual de la SAI in vivo expresada como SI (par metro determinado utilizando el Modelo Mínimo de Bergman modificado con insulina [MMins]), em 11 sujetos con un amplio rango de SAI in vivo. SI (primer estudio) varió entre 0,82 y 8,48 x 10(-4) min(-1)/muU.mL (4,43 + 2,85 x 10(-4) min(-1)/muU.ml; média + DS) y presentó una correlación altamente significativa con SI (segundo estudio) (r = 0,89; p = 0,0002). El coeficiente de variación medio fue del 20,9 + 13,9 por ciento). La SAI in vivo fue também determinada analizando la tasa de caída de los niveles de glucemia luego del suministro IV de 0,025 U/kg de insulina cristalina humana (método de Bonora modificado o BBD), en 11 sujetos. La SAI in vivo determinada por BBD varió entre 21 y 234 mumol/ml/min (134 + 64,8 mumol/ml/min, média + DS). No se observaron hipoglucemias durante los estudios. La correlación entre los valores de SI obtenidos del MMins y los resultados del BBD fue altamente significativa ( r= 0,89, p = 0,0002). Los resultados del presente trabajo sugieren que el MMins tiene una adecuada reproducibilidad intra-sujeto y que el BBD constituye una medida aproximada de la SAI in vivo siendo particularmente aplicable cuando es necesaria la practica de un procedimiento de r pida ejecución y menor complejidad y costo.