Publications by authors named "Paula Carrasco"

34 Publications

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer.

Sci Rep 2021 Apr 14;11(1):8111. Epub 2021 Apr 14.

Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), University General Hospital of Castellon, Av Benicasim s/n, 12004, Castellón, Spain.

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-86928-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047030PMC
April 2021

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Sci Total Environ 2021 Mar 20;782:146654. Epub 2021 Mar 20.

Epidemiology and Environmental Health Joint Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, FISABIO-Universitat Jaume I-Universitat de València, Av. Catalunya 21, 46020 Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029 Madrid, Spain.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 μg/L and 0.97 μg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (p < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (p < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (p < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.146654DOI Listing
March 2021

Postoperative Intestinal Fistula in Primary Advanced Ovarian Cancer Surgery.

Cancer Manag Res 2021 6;13:13-23. Epub 2021 Jan 6.

Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), University General Hospital of Castellon, Castellón, Spain.

Background: Advanced ovarian cancer (AOC) requires an aggressive surgery with large visceral resections in order to achieve an optimal or complete cytoreduction and increase the patient's survival. However, the surgical aggressiveness in the treatment of AOC is not exempt from major complications, such as the gastrointestinal fistula (GIF), which stands out among others due to its high morbidity and mortality.

Methods: We evaluated the clinicopathological features in patients with AOC and their association with GI. Data for 107 patients with AOC who underwent primary debulking surgery were analyzed retrospectively. Clinicopathological features, including demographic, surgical procedures and follow-up data, were analyzed in relation to GIF.

Results: GIF was present in 11% of patients in the study, 5 (4.5%) and 7 (6.4%) of colorectal and small bowel origin, respectively. GIF was significantly associated with peritoneal cancer index (PCI) >20, more than 2 visceral resections, and multiple digestive resections. Overall and disease-free survival were also associated with GIF. Multivariate analysis identified partial bowel obstruction and operative bleeding as independent prognostic factors for survival. The presence of GIF is positively associated with poor prognosis in patients with AOC.

Conclusion: Given the importance of successful cytoreductive surgery in AOC, the assessment of the amount of tumor and the aggressiveness of the surgery to avoid the occurrence of GIF become a priority in patients with AOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S280511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797294PMC
January 2021

Association of a traditional Mediterranean diet and non-Mediterranean dietary scores with all-cause and cause-specific mortality: prospective findings from the Moli-sani Study.

Eur J Nutr 2021 Mar 21;60(2):729-746. Epub 2020 May 21.

Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell'Elettronica, 86077, Pozzilli, IS, Italy.

Purpose: To evaluate in an Italian general population, the association with mortality of a traditional Mediterranean diet (MD) and non-Mediterranean dietary (non-MD) patterns, and their combined effect, and to test some biomarkers of cardiovascular (CVD) risk as potential mediators of such associations.

Methods: Longitudinal analysis on 22,849 men and women aged ≥ 35 years, recruited in the Moli-sani Study (2005-2010), followed up for 8.2 years (median). The MD was assessed by the Mediterranean diet score (MDS). The Dietary  Approaches to Stop Hypertension (DASH), the Palaeolithic diet, and the Nordic diet were chosen as reportedly healthy non-MD patterns. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression.

Results: Participants reaching higher MDS or DASH diet score experienced lower risk of both all-cause (HR 0.77; 95% CI 0.66-0.90 and 0.81; 0.69-0.96, respectively, highest vs lowest quartile) and CVD (0.77; 0.59-1.00 and 0.81; 0.69-0.96, respectively) death risk; risk reduction associated with the Palaeolithic diet was limited to total and other cause death, whereas the Nordic diet did not alter risk of mortality. Increasing adherence to MD was associated with higher survival in each stratum of non-MD diets. Biomarkers of glucose metabolism accounted for 7% and 21.6% of the association between either MDS or DASH diet, respectively, with total mortality risk.

Conclusions: Both the traditional MD and DASH diet may reduce risk of all-cause mortality among Italians, as well as risk of dying from cardiovascular causes. The Palaeolithic diet did not appear to reduce cardiovascular risk, while the Nordic eating pattern was unlikely to be associated with any substantial health advantage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-020-02272-7DOI Listing
March 2021

Chili Pepper Consumption and Mortality in Italian Adults.

J Am Coll Cardiol 2019 12;74(25):3139-3149

Department of Epidemiology and Prevention, IRCCS Neuromed, Via dell'Elettronica, Pozzilli, Italy; Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy.

Background: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations.

Objectives: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association.

Methods: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week.

Results: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations.

Conclusions: In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2019.09.068DOI Listing
December 2019

Maternal copper status and neuropsychological development in infants and preschool children.

Int J Hyg Environ Health 2019 04 1;222(3):503-512. Epub 2019 Feb 1.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Av. Catalunya 21, 46020 Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029 Madrid, Spain. Electronic address:

Introduction: Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development.

Methods: Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development.

Results: The mean ± standard deviation of maternal Cu concentrations was 1606 ± 272 μg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = -0.051; 95% confidence intervals [CI]: -0.102, -0.001) and the MSCA verbal scale (beta = -0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938μg/L).

Conclusion: The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijheh.2019.01.007DOI Listing
April 2019

Reduced mortality risk by a polyphenol-rich diet: An analysis from the Moli-sani study.

Nutrition 2018 04 28;48:87-95. Epub 2017 Nov 28.

Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy; Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Objectives: The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood. The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation, in what we believe to be a novel, holistic approach.

Methods: We analyzed 21 302 participants (10 980 women and 10 322 men, aged ≥35 y) from the Moli-sani cohort. The participants were followed up for a median of 8.3 y. The European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ) was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone, and lignan intakes were calculated using European Food Information Resource-Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet.

Results: Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption (hazard ratio [HR] < 1; P <0.05). Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk (HR <1; P <0.05). When cause-specific mortality rates were considered, similar effects were observed for cardiocerebrovascular and cancer mortality (HR <1; P <0.05).

Conclusions: The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population, possibly through an antiinflammatory mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nut.2017.11.012DOI Listing
April 2018

Serum vitamin D deficiency and risk of hospitalization for heart failure: Prospective results from the Moli-sani study.

Nutr Metab Cardiovasc Dis 2018 03 7;28(3):298-307. Epub 2017 Dec 7.

Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli (IS), Italy; Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, 21100 Varese, Italy.

Background And Aims: Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults.

Methods And Results: 19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF.

Conclusion: Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2017.11.008DOI Listing
March 2018

Moderate Alcohol Consumption Is Associated With Lower Risk for Heart Failure But Not Atrial Fibrillation.

JACC Heart Fail 2017 11 11;5(11):837-844. Epub 2017 Oct 11.

Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy; Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Objectives: The aim of this study was to assess the hypothesis that alcohol consumption is associated with onset of atrial fibrillation (AF) and/or heart failure (HF).

Background: The connection between ethanol intake and AF or HF remains controversial.

Methods: The study population was 22,824 AF- or HF-free subjects (48% men, age ≥35 years) randomly recruited from the general population included in the Moli-sani study, for whom complete data on HF, AF, and alcohol consumption were available. The cohort was followed up to December 31, 2015, for a median of 8.2 years (183,912 person-years). Incident cases were identified through linkage to the Molise regional archive of hospital discharges. Hazard ratios were calculated using Cox proportional hazard models and cubic spline regression.

Results: A total of 943 incident cases of HF and 554 of AF were identified. In comparison with never drinkers, both former and occasional drinkers showed comparable risk for developing HF. Drinking alcohol in the range of 1 to 4 drinks/day was associated with a lower risk for HF, with a 22% maximum risk reduction at 20 g/day, independent of common confounders. In contrast, no association of alcohol consumption with onset of AF was observed. Very similar results were obtained after restriction of the analyses to regular or only wine drinkers or according to sex, age, social status, or adherence to the Mediterranean diet.

Conclusions: Consumption of alcohol in moderation was associated with a lower incidence of HF but not with development of AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2017.08.017DOI Listing
November 2017

Fish intake is associated with lower cardiovascular risk in a Mediterranean population: Prospective results from the Moli-sani study.

Nutr Metab Cardiovasc Dis 2017 Oct 23;27(10):865-873. Epub 2017 Aug 23.

Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, IS, Italy; Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.

Background And Aims: Fish consumption reportedly reduces the risk of heart disease, but the evidence of cardiovascular advantages associated with fish intake within Mediterranean cohorts is limited. The aim of this study was to test the association between fish intake and risk of composite coronary heart disease (CHD) and stroke in a large population-based cohort adhering to Mediterranean Diet.

Methods And Results: Prospective analysis on 20,969 subjects free from cardiovascular disease at baseline, enrolled in the Moli-sani study (2005-2010). Food intake was recorded by the Italian version of the EPIC food frequency questionnaire. Hazard ratios were calculated by using multivariable Cox-proportional hazard models. During a median follow-up of 4.3 years, a total of 352 events occurred (n of CHD = 287 and n of stroke = 66). After adjustment for a large panel of covariates, fish intake ≥4 times per week was associated with 40% reduced risk of composite CHD and stroke (HR = 0.60; 95%CI 0.40-0.90), and with 40% lower risk of CHD (HR = 0.60; 95%CI 0.38-0.94) as compared with subjects in the lowest category of intake (<2 times/week). A similar trend of protection was found for stroke risk although results were not significant (HR = 0.62; 95%CI 0.26-1.51). When fish types were considered, protection against the composite outcome and CHD was confined to fatty fish intake.

Conclusions: Fish intake was associated with reduced risk of composite fatal and non-fatal CHD and stroke in a general Mediterranean population. The favourable association was likely to be driven by fatty fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2017.08.004DOI Listing
October 2017

Hepatocellular carcinoma in identical twins in Chile: case report.

Ecancermedicalscience 2016 21;10:708. Epub 2016 Dec 21.

Radiation Oncology, Clínica Alemana, Temuco, Chile; Instituto Oncològico Fundación Arturo López Pérez, Rancagua 878, Providencia Santiago, Chile.

Liver cancer is the second leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary malignant liver tumour, with a typically poor prognosis, growing incidence and a well-documented relationship with chronic inflammation factors of the liver tissue. Despite the fact that family medical history has been identified as a risk factor for the development of HCC, its significance in terms of etiopathogenesis and prognosis is not well documented. With a view to contributing to this discussion, we will report the clinical case of two identical twins with HCC, both diagnosed within a short period of time, by providing relevant clinical data, and relating this to other medical literature reports that could contribute to a deeper understanding of this illness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3332/ecancer.2016.708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221639PMC
December 2016

Age-sex-specific ranges of platelet count and all-cause mortality: prospective findings from the MOLI-SANI study.

Blood 2016 Mar 10;127(12):1614-6. Epub 2016 Feb 10.

Department of Epidemiology and Prevention, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2016-01-692814DOI Listing
March 2016

Nut consumption is inversely associated with both cancer and total mortality in a Mediterranean population: prospective results from the Moli-sani study.

Br J Nutr 2015 Sep;114(5):804-11

1Department of Epidemiology and Prevention,IRCCS Istituto Neurologico Mediterraneo,Neuromed,86077 Pozzilli,Isernia,Italy.

Nut intake has been associated with reduced inflammatory status and lower risk of CVD and mortality. The aim of this study was to examine the relationship between nut consumption and mortality and the role of inflammation. We conducted a population-based prospective investigation on 19 386 subjects enrolled in the Moli-sani study. Food intake was recorded by the Italian version of the European Project Investigation into Cancer and Nutrition FFQ. C-reactive protein, leucocyte and platelet counts and the neutrophil:lymphocyte ratio were used as biomarkers of low-grade inflammation. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard models. During a median follow-up of 4·3 years, 334 all-cause deaths occurred. As compared with subjects who never ate nuts, rare intake (≤2 times/month) was inversely associated with mortality (multivariable HR=0·68; 95 % CI 0·54, 0·87). At intake ≥8 times/month, a greater protection was observed (HR=0·53; 0·32, 0·90). Nut intake (v. no intake) conveyed a higher protection to individuals poorly adhering to the Mediterranean diet (MD). A significant reduction in cancer deaths (HR=0·64; 95 % CI 0·44, 0·94) was also observed, whereas the impact on CVD deaths was limited to an inverse, but not significant, trend. Biomarkers of low-grade inflammation were reduced in nut consumers but did not account for the association with mortality. In conclusion, nut intake was associated with reduced cancer and total mortality. The protection was stronger in individuals with lower adherence to MD, whereas it was similar in high-risk groups (diabetics, obese, smokers or those with the metabolic syndrome), as compared with low-risk subjects. Inflammation did not explain the observed relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114515002378DOI Listing
September 2015

T-wave axis deviation is associated with biomarkers of low-grade inflammation. Findings from the MOLI-SANI study.

Thromb Haemost 2015 Nov 9;114(6):1199-206. Epub 2015 Jul 9.

Licia Iacoviello, Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Via dell'Elettronica, 86077 Pozzilli (Isernia), Italy, Tel.: +39 0865929664, Fax:+39 0865927575, E-mail:

T-wave axis deviation (TDev) may help identifying subjects at risk for major cardiac events and mortality, but the pathogenesis of TDev is not well established; in particular, the possible association between TDev and inflammation is unexplored and unknown. We aimed at investigating the association between low-grade inflammation and TDev abnormalities by conducting a cross-sectional analysis on 17,507 subjects apparently free from coronary heart and haematological diseases enrolled in the MOLI-SANI study. TDev was measured from a standard 12-lead resting electrocardiogram. High sensitivity (Hs) C-reactive protein (CRP), leukocyte (WBC) and platelet counts, neutrophil or granulocyte to lymphocyte ratios were used as markers of inflammation. In multivariable model subjects reporting high CRP levels had higher odds of having borderline and abnormal TDev (OR=1.70; 95 %CI: 1.53-1.90 and OR=1.72; 95 %CI: 1.23-2.41, respectively); the association was still significant, although reduced, after controlling for body mass index (OR=1.17; 95 %CI: 1.05-1.32, for borderline and OR=1.46; 95 %CI: 1.03-2.08, for abnormal). Similarly, higher neutrophil or granulocyte to lymphocyte ratios were associated with increased odds of having abnormal TDev. Neither platelet nor leukocyte counts were associated with abnormal TDev. The relationship between CRP with TDev abnormalities was significantly stronger in men, in non- obese or normotensive individuals, and in those without metabolic syndrome. In conclusion, C-reactive protein and some cellular biomarkers of inflammation such as granulocyte or neutrophil to lymphocyte ratios were independently associated with abnormal TDev, especially in subjects at low CVD risk. These results suggest that a low-grade inflammation likely contributes to the pathogenesis of T- wave axis deviation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH15-02-0177DOI Listing
November 2015

Adherence to the Mediterranean diet is associated with lower platelet and leukocyte counts: results from the Moli-sani study.

Blood 2014 May 31;123(19):3037-44. Epub 2014 Mar 31.

Department of Epidemiology and Prevention, Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.

Platelet (PLT) and white blood cell (WBC) counts are 2 markers of inflammation and have been linked to the risk for cerebrovascular and coronary heart disease. A Mediterranean diet (MD) has been associated with reduced inflammation and mortality for major chronic diseases. We aimed at evaluating the association between the MD and both PLT and WBC counts. This cross-sectional analysis in a population-based cohort study included 14,586 healthy Italian citizens enrolled within the Moli-sani study. Adherence to MD was appraised by either the MD Score (MDS) or the Italian Mediterranean Index (IMI). PLT and WBC counts were both inversely related to MD adherence (MDS: P < .0001 and P = .008, respectively). As compared with those with poorer MD adherence, subjects with greater adherence had both reduced odds of being in the highest PLT-count group (MDS: odds ratio = 0.50; 95% confidence interval, 0.31-0.80) and increased odds of being in the lowest WBC-count group (IMI: odds ratio = 1.41; 95% confidence interval, 1.07-1.86). The association between WBC count and MDS disappeared when further adjusted for PLT count, whereas the association between PLT count and the MD was not affected by adjustment for WBCs. Food antioxidant and dietary fiber content modified the inverse association between MDS and WBC count and partially accounted for the association with PLTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2013-12-541672DOI Listing
May 2014

Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

Diabetes Care 2013 Nov 13;36(11):3803-11. Epub 2013 Aug 13.

Corresponding author: Dolores Corella,

Objective: Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.

Research Design And Methods: A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events.

Results: The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36-6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49-1.87]; P = 0.892 for TT compared with CC).

Conclusions: Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc13-0955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816851PMC
November 2013

Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption.

PLoS One 2012 21;7(12):e52344. Epub 2012 Dec 21.

Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain.

Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood.

Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake.

Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed.

Results: FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR=1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P=0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P=0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P=0.001).

Conclusion: Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052344PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528751PMC
June 2013

[Radio and chemotherapy in gallbladder cancer: a Latin American Consensus].

Rev Med Chil 2012 Aug;140(8):1060-6

Instituto Oncológico, Universidad de Valparaíso, Viña del Mar, Chile.

No randomized controlled trials have been conducted in gallbladder cancer to establish standard treatments. We therefore conducted the first Latin American Consensus meeting for the management of gallbladder cancer. In this paper we report the conclusions of the experts' panel for (neo) adjuvant treatment of resectable gallbladder cancer. These are based on the review of the literature, the discussion of the participating experts and the vote of the assistants (surgical oncologists, medical oncologists, radiation oncologists and others). The reviewed topics were the role or adjuvant radiochemotherapy in T1 bN0M0, T2-3 N0-1M0 and T4 N0-1 M0 disease and doses, schedules and drugs for radiochemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4067/S0034-98872012000800015DOI Listing
August 2012

The Moli-sani project: computerized ECG database in a population-based cohort study.

J Electrocardiol 2012 Nov-Dec;45(6):684-9. Epub 2012 Sep 27.

Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica, Campobasso, Italy.

Computerized electrocardiogram (ECG) acquisition and interpretation may be extremely useful in handling analysis of data from large cohort studies and exploit research on the use of ECG data as prognostic markers for cardiovascular disease. The Moli-sani project (http://www.moli-sani.org) is a population-based cohort study aiming at evaluating the risk factors linked to chronic-degenerative disease with particular regard to cardiovascular disease and cancer and intermediate metabolic phenotypes such as hypertension, diabetes, dyslipidemia, obesity, and metabolic syndrome. Between March 2005 and April 2010, 24 325 people aged 35 years or older, living in the Molise region (Italy), were randomly recruited. A follow-up based on linkage with hospital discharge records and mortality regional registry and reexamination of the cohort is ongoing and will be repeated at prefixed times. Each subject was administered questionnaires on personal and medical history, food consumption, quality of life (FS36), and psychometry. Plasma serum, cellular pellet, and urinary spots were stored in liquid nitrogen. Subjects were measured blood pressure, weight, height, and waist and hip circumferences, and underwent spirometry to evaluate pulmonary diffusion capacity, gas diffusion, and pulmonary volumes. Standard 12-lead resting ECG was performed by a Cardiette ar2100-view electrocardiograph and tracings stored in digital standard communication protocol format for subsequent analysis. The digital ECG database of the Moli-sani project is currently being used to assess the association between physiologic variables and pathophyiosiologic conditions and parameters derived from the ECG signal. This computerized ECG database represents a unique opportunity to identify and assess prognostic factors associated with cardiovascular and metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jelectrocard.2012.07.008DOI Listing
May 2013

Relation between pulmonary function and 10-year risk for cardiovascular disease among healthy men and women in Italy: the Moli-sani Project.

Eur J Prev Cardiol 2013 Oct 18;20(5):862-71. Epub 2012 May 18.

Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, Fondazione di Ricerca e Cura "Giovanni Paolo II" Catholic University, Campobasso, Italy.

Background: Pulmonary dysfunction could influence the onset and the evolution of cardiovascular disorders. This study evaluated whether pulmonary dysfunction based on spirometry, plethysmography and carbon monoxide diffusion test is associated with the estimated risk of cardiovascular disease in 10 years.

Design: We performed a cross-sectional general population-based cohort study.

Methods: The Moli-sani Project is a population-based cohort study of subjects aged ≥35 years, randomly recruited from the general population in Italy. Cardiovascular risk in 10 years was predicted by the CUORE score which provides an estimate of the probability of a first coronary or cerebrovascular event in the next 10 years, based on a risk equation derived from Italian cohorts. Out of 12,933 subjects with high-quality flow/volume manoeuvre, 8,132 subjects had suitable plethysmography and 3,422 carbon monoxide diffusion (carbon monoxide alveolar diffusion test [DLCO]).

Results: In multivariate analyses, reduced pulmonary function expressed by forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and total lung capacity (TLC) were inversely associated with CUORE score both in men and in women, independently of other risk factors such as age, height, smoking habits, total cigarettes exposure (pack-years), pulmonary disease, body mass index, social status and physical activity. In contrast, there was no association between FEV1/FVC ratio, residual volume, DLCO and CUORE risk score.

Conclusions: In both genders from an adult general Italian population, pulmonary function decline is associated with increased cardiovascular risk. These results suggest that pulmonary monitoring could be useful to more accurately predict cardiovascular risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487312447904DOI Listing
October 2013

White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population: results from the MOLI-SANI project.

Haematologica 2011 Aug 5;96(8):1180-8. Epub 2011 May 5.

Research Laboratories, University with Fondazione di Ricerca e Cura Giovanni Paolo II for High Technology Research and Education in Biomedical Sciences, Catholic University, Largo Gemelli 1, Campobasso, Italy.

Background: The understanding of non-genetic regulation of platelet indices--platelet count, plateletcrit, mean platelet volume, and platelet distribution width--is limited. The association of these platelet indices with a number of biochemical, environmental and clinical variables was studied in a large cohort of the general population.

Design And Methods: Men and women (n=18,097, 52% women, 56±12 years) were randomly recruited from various villages in Molise (Italy) in the framework of the population-based cohort study "Moli-sani". Hemochromocytometric analyses were performed using an automatic analyzer (Beckman Coulter, IL, Milan, Italy). Associations of platelet indices with dependent variables were investigated by multivariable linear regression analysis.

Results: Full models including age, sex, body mass index, blood pressure, smoking, menopause, white and red blood cell counts, mean corpuscular volume, D-dimers, C-reactive protein, high-density lipoproteins, low-density lipoproteins, triglycerides, glucose, and drug use explained 16%, 21%, 1.9% and 4.7% of platelet count, plateletcrit, mean platelet volume and platelet distribution width variability, respectively; variables that appeared to be most strongly associated were white blood cell count, age, and sex. Platelet count, mean platelet volume and plateletcrit were positively associated with white blood cell count, while platelet distribution width was negatively associated with white blood cell count. Platelet count and plateletcrit were also positively associated with C-reactive protein and D-dimers (P<0.0001). Each of the other variables, although associated with platelet indices in a statistically significant manner, only explained less than 0.5% of their variability. Platelet indices varied across Molise villages, independently of any other platelet count determinant or characteristics of the villages.

Conclusions: The association of platelet indices with white blood cell count, C-reactive protein and D-dimers in a general population underline the relation between platelets and inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2011.043042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148912PMC
August 2011

Association of the LCT-13910C>T polymorphism with obesity and its modulation by dairy products in a Mediterranean population.

Obesity (Silver Spring) 2011 Aug 30;19(8):1707-14. Epub 2010 Dec 30.

Department of Preventive Medicine and Public Health, Genetic and Molecular Epidemiology Unit School of Medicine, University of Valencia, Valencia, Spain.

The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 ± 4.2 vs. 30.6 ± 4.2 kg/m(2); P = 0.003) and lower waist circumference (101.1 ± 11.8 vs. 103.5 ± 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also significantly higher in T-allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/oby.2010.320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426982PMC
August 2011

Typical breakfast food consumption and risk factors for cardiovascular disease in a large sample of Italian adults.

Nutr Metab Cardiovasc Dis 2012 Apr 18;22(4):347-54. Epub 2010 Nov 18.

Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, John Paul II Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Largo Gemelli 1, 86100 Campobasso, Italy.

Background And Aims: The overall consumption of foods most frequently consumed in a typical Italian breakfast might be associated with a better cardiovascular risk profile in Italian adults.

Method Sand Results: 18,177 subjects (53,2% women), aged ≥ 35 yrs, randomly selected from the Moli-sani Project population were studied. The European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ was used for dietary assessment. To derive breakfast pattern, an "a priori" approach was used: firstly, foods typical of the Italian breakfast were selected: milk, coffee, tea, yogurt, crispbread/rusks, breakfast cereals, brioche, biscuits, honey, sugar and jam. The breakfast score was obtained adding the amounts of all selected foods, expressed in grams/day, previously standardized to mean zero and standard deviation 1. Subjects showing a higher breakfast score appeared to be younger, more frequently women or smokers, with higher social status but less likely practicing physical activity. After multivariable analyses, subjects with a higher breakfast food consumption had a lower risk to have high body mass index, abdominal obesity, systolic and diastolic blood pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all) and C Reactive Protein (P = 0.022). The associations were unrelated to age, sex, smoking, obesity, physical activity and social status. Subjects with a higher food breakfast score also showed a better physical healthy status score, a lower risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P < 0.0001 for both women and men).

Conclusion: Consumption of typical Italian breakfast foods positively affects CVD risk profile in an adult Italian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2010.07.006DOI Listing
April 2012

Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation in splanchnic vein thrombosis.

Eur J Haematol 2011 Feb 29;86(2):167-72. Epub 2010 Dec 29.

Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Avd. Campanar 21, Valencia, Spain.

Introduction: The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location.

Objective: To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT.

Material And Methods: We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd-Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls.

Results: In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P =0.044). After adjusting for total cholesterol, differences disappeared (P =0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P =0.199), even after adjusting for age and total cholesterol (P =0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P =0.253) or with SVT subtypes (P =0.885). No association was found between HH (>15 μm) and the TT genotype in cases (P =0.404), controls (P =0.178), or in the different SVT subtypes (P =0.495).

Conclusions: Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0609.2010.01551.xDOI Listing
February 2011

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population.

J Lipid Res 2010 Sep 25;51(9):2798-807. Epub 2010 Jun 25.

Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain.

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.P005199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918462PMC
September 2010

Common cholesteryl ester transfer protein gene variation related to high-density lipoprotein cholesterol is not associated with decreased coronary heart disease risk after a 10-year follow-up in a Mediterranean cohort: Modulation by alcohol consumption.

Atherosclerosis 2010 Aug 27;211(2):531-8. Epub 2010 Mar 27.

Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine, School of Medicine, University of Valencia, Valencia, Spain.

Objective: Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.

Methods: A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.

Results: Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P<0.001), no protective effect of the B2 allele against CHD incidence was observed. Thus, in comparison with B1B1 subjects, the adjusted CHD risk of B1B2 was OR: 1.00, 95% CI: 0.80-1.26; P=0.982, and that of B2B2 was OR: 1.16, 95% CI: 0.84-1.61; P=0.374. These results did not change after adjustment for HDL-C. No significant interaction between alcohol consumption and the CETP-TaqIB polymorphism in determining HDL-C was found. However, a different effect of this polymorphism on CHD risk in drinkers and non-drinkers was observed. In non-drinkers, the B2B2 genotype was associated with a non-significant lower CHD risk, whereas in drinkers it was associated with a greater risk (OR: 1.55, 95% CI: 1.05-2.29; P=0.026). We also observed that in diabetics (11% cases and 7.4% controls), the B2 allele was significantly associated with higher CHD risk.

Conclusions: In this Mediterranean population, the CETP-TaqIB polymorphism was not associated with a lower CHD incidence, and its effect was modulated by alcohol and possibly by diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2010.03.026DOI Listing
August 2010

Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain.

Br J Nutr 2010 Jun 27;103(12):1808-16. Epub 2010 Jan 27.

Faculty of Medicine and Health Science, Universitat Rovira i Virgili, Spain.

The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study, a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk. The FFQ was administered twice (FFQ1 and FFQ2) to explore reproducibility at 1 year. Four 3 d dietary records (DR) were used as reference to explore validity; participants therefore recorded their food intake over 12 d in the course of 1 year. The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR. A total of 158 men and women (aged 55-80 years) were asked not to modify their dietary habits during the study period. Reproducibility for food groups, energy and nutrient intake, explored by the Pearson correlation coefficient (r) ranged 0.50-0.82, and the intraclass correlation coefficient (ICC) ranged from 0.63 to 0.90. The FFQ2 tended to report higher energy and nutrient intake than the DR. The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged (r) from 0.24 to 0.72, while the range of the ICC was between 0.40 and 0.84. With regard to food groups, 68-83 % of individuals were in the same or adjacent quintile in both methods, a figure which decreased to 55-75 % for energy and nutrient intake. We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114509993837DOI Listing
June 2010

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population.

Free Radic Res 2009 Dec;43(12):1179-86

Department of Biochemistry and Molecular Biology, Faculty of Medicine, School of Medicine, University of Valencia, Valencia, Spain.

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7'8'-dihydro-2'-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10715760903247231DOI Listing
December 2009

Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts.

J Nutr 2009 Jan 3;139(1):128-34. Epub 2008 Dec 3.

Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain.

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 +/- 4.82 in GG vs. 4.74 +/- 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 +/- 114.8 in GG vs. 243.0 +/- 107.1 microg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3945/jn.108.093054DOI Listing
January 2009

General principles regarding the use of adult stem cells.

Cell Prolif 2008 Feb;41 Suppl 1:78-84

Institute of Bioethics, School of Medicine A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy.

With only a few, almost inevitable exceptions, biomedical research has developed within the last 50 years under the tutelage of ethical standards of notable precision. In the vast world of scientific investigation, few disciplines can boast of having realized documents of such ethical rigour, and respect for the integrity and intrinsic value of the human person has been one of the cardinal principles of the researcher. Research is intrinsic to the medical profession; the reward of research is knowledge and its techniques are ordered towards maintenance of human health. Since this end concerns human beings, it demands an extremely rigorous ethical approach. Ethical aspects are present from the first moments of the experimental project and occur on three levels: choice of the objectives, selection and use of the appropriate means for the study, and application of resultant new discoveries. Today, our moral attention cannot be reduced to a cost-benefit analysis. Biomedical sciences and medicine have overlapping areas of interest that can be sources of tension: the good of the subject versus scientific utility; profit versus complexity of research; liberty versus ethical and juridical bonds; the public versus the private; and the individual versus the community. Here, I attempt to formulate some essential principles that should guarantee humane measures for research on humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2184.2008.00482.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496655PMC
February 2008