Augusto Di Castelnuovo

Meta-Analysis of Wine and Beer Consumption in Relation to Vascular Risk

Background—Many epidemiological studies have evaluated whether different alcoholic beverages protect against cardiovascular disease. We performed a meta-analysis of 26 studies on the relationship between wine or beer consumption and vascular risk. Methods and Results—General variance-based method and fitting models were applied to pooled data derived from 26 studies that gave a quantitative estimation of the vascular risk associated with either beverage consumption. From 13 studies involving 209 418 persons, the relative risk of vascular disease associated with wine intake was 0.68 (95% confidence interval, 0.59 to 0.77) relative to nondrinkers. There was strong evidence from 10 studies involving 176 042 persons to support a J-shaped relationship between different amounts of wine intake and vascular risk. A statistically significant inverse association was found up to a daily intake of 150 mL of wine. The overall relative risk of moderate beer consumption, which was measured in 15 studies involving 208 036 persons, was 0.78 (95% confidence interval, 0.70 to 0.86). However, no significant relationship between different amounts of beer intake and vascular risk was found after meta-analyzing 7 studies involving 136 382 persons. Conclusions—These findings show evidence of a significant inverse association between light-to-moderate wine consumption and vascular risk. A similar, although smaller association was also apparent in beer consumption studies. The latter finding, however, is difficult to interpret because no meaningful relationship could be found between different amounts of beer intake and vascular risk.

The −174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial Fibrillation an Inflammatory Complication?

Background—It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the −174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results—In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P <0.001 for difference between the area under the curve). Conclusion—The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Polymorphisms in the Coagulation Factor VII Gene and the Risk of Myocardial Infarction

BACKGROUND High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established. METHODS We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured. RESULTS Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34). CONCLUSIONS Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.

Alcohol Consumption and Mortality in Patients With Cardiovascular Disease. A Meta-Analysis

OBJECTIVES The purpose of this study was to quantify the relation between alcohol consumption and cardiovascular and total mortality in patients with a history of cardiovascular events. BACKGROUND Regular, moderate alcohol consumption by healthy people is associated with lower cardiovascular and all-cause mortality. No extensive meta-analysis is presently available on the possible association of alcohol consumption with secondary events in patients with cardiovascular disease. METHODS Articles were retrieved through October 2009 by search in PubMed and EMBASE. Fifty-four publications were identified, but only 8 were selected for our analyses, including 16,351 patients with a history of cardiovascular disease. Secondary events were cardiovascular or all-cause mortality. All selected studies were prospective. Data were pooled with a weighted, least-squares regression analysis of second-order fractional polynomial models. RESULTS The meta-analysis on cardiovascular mortality showed a J-shaped pooled curve with a significant maximal protection (average 22%) by alcohol at approximately 26 g/day. In the meta-analysis on mortality for any cause, J-shaped pooled curves were observed in the overall analysis (average maximal protection of 18% in the range of 5 to 10 g/day) and in all subgroups according to either the type of patients or the characteristics of the studies. CONCLUSIONS In patients with cardiovascular disease, light to moderate alcohol consumption (5 to 25 g/day) was significantly associated with a lower incidence of cardiovascular and all-cause mortality.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

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

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.

Low income is associated with poor adherence to a Mediterranean diet and a higher prevalence of obesity: cross-sectional results from the Moli-sani study

Objectives To examine cross-sectional associations of socioeconomic status (ie, income and education) with an adherence to a Mediterranean dietary pattern and obesity prevalence. Design Cross-sectional study on a sample of Italian subjects enrolled in the Moli-sani Project, a population-based cohort study. The Italian EPIC food frequency questionnaire was used to determine food intake. Adherence to a Mediterranean diet (MD) was appraised according to both the Mediterranean score elaborated by Trichopoulou (MDS) and the novel Italian Mediterranean Index (IMI) and to the a posteriori scores derived from principal component analysis. Four income categories were identified. Setting Molise region, Italy. Participants 13 262 subjects (mean age 53±11, 50% men) out of 24 318 citizens (age ≥35) randomly enrolled in the Moli-sani Project. Main outcomes Dietary patterns and risk factors for cardiovascular disease. Results Household higher income were significantly associated with greater adherence to an MD (p<0.0001) and to Olive oil and Vegetables dietary pattern in a multivariable model including age, sex, daily energy intake, body mass index, physical activity, smoking, alcohol consumption, education and marital status. The odds of having the highest adherence to an MD clearly increased according to income levels. People having the highest income had 54% (95% CI 21% to 97%, MDS) or 72% (95% CI 34% to 121%, IMI) higher probability to stick to an MD-like eating pattern than those in the lowest-income group. Obesity prevalence was higher in the lowest-income group (36%) in comparison with the highest-income category (20%, p<0.0001). Income was associated with dietary patterns in all categories of education. Conclusions A higher income and education are independently associated with a greater adherence to MD-like eating patterns and a lower prevalence of obesity.

Cardiovascular and Overall Mortality Risk in Relation to Alcohol Consumption in Patients With Cardiovascular Disease

Alcohol, in striking contrast to tobacco and illicit drugs, is linked to an extensively documented J-shaped dose-effect curve, with regular moderate consumption reducing cardiovascular and overall mortality,1 whereas excessive or binge drinking has the opposite effect.1,2 Data indicative of a lower risk of cardiovascular events among moderate drinkers in apparently healthy people are extensive and consistent, whereas the role of alcohol intake among patients with cardiovascular disease (CVD) is less clear.3 Among the factors that contribute to prevention in survivors of primary cardiovascular events, lifestyle and dietary habits play a major role. However, guidelines in this area are based either on studies of apparently healthy subjects or on a few studies of cardiovascular patients.4,5 In particular, recommendations about alcohol consumption in patients with previous CVD reflect experts’ consensus rather than circumstantial evidence.3,6 The US Food and Drug Administration warns that heart disease patients should stop drinking, and people who take aspirin regularly should not drink alcohol.7 However, in the American Heart Association/American College of Cardiology guidelines for secondary prevention,5 CVD patients are encouraged to maintain a lifestyle that includes drinking alcohol in moderation. The “Diet and Lifestyle Recommendations” scientific statement from the American Heart Association Nutrition Committee8 advises, “If you consume alcohol, do so in moderation (equivalent of no more than 1 drink in women or 2 drinks in men per day).” The latter statement is largely accepted within the scientific community, definitely when referring to healthy people, although some would advise people to abstain completely rather than encouraging them to drink small amounts regularly. It has in fact been suggested that the consumption of alcohol for certain health benefits should not be encouraged, because the harm would far outweigh the gain, especially among poor populations and in low-income countries, where the …

Pharmacokinetic and Pharmacodynamic Differences Between Two Low Dosages of Aspirin May Affect Therapeutic Outcomes

AbstractBackground: Meta-analyses of the prevention of major vascular events by aspirin suggest therapeutic equivalence of all dosages. However, the optimal dosage still remains problematic, and a recent trial found aspirin 160 mg/day to be more effective than 80 mg/day for secondary prevention of ischaemic stroke. Objective: To evaluate two low dosages of aspirin in terms of pharmacokinetics and pharmacodynamics (inhibition of platelet thromboxane generation and urinary excretion of thromboxane and prostacyclin metabolites). Design and Participants: A randomised cross-over study was performed in 16 healthy volunteers (9 women and 7 men, 33.8 ± 5.1 years old) given enteric-coated aspirin 80 or 160 mg/day for 7 days. Methods: Plasma concentrations of salicylate and aspirin were measured by high-performance liquid chromatography (HPLC) after both the first and the last dose (days 1 and 7). The usual pharmacokinetic parameters were then derived. Serum thromboxane B2 (TxB2) was measured by radioimmunoassay. The urinary excretion of 11-dehydro-TxB2 and 2,3-dinor-6-keto-prostaglandin F1α were measured on 8-hour urine samples by immunoassay after extraction and HPLC separation, both before and after 7 days of drug administration. Results: With the 160mg dosage, but not with the 80mg dosage, higher concentrations of aspirin were found at day 7 compared with day 1. For aspirin 80 mg/day, 24-hour area under the concentration-time curve (AUC24) was similar on days 1 and 7 (569 ± 339 vs 605 ± 377 γ · h/L), but increased from 904 ± 356 ⧎g · h/L on day 1 to 1355 ± 883 ⧎g · h/L on day 7 with the higher dosage. Similarly, the AUC24 for salicylate was similar on days 1 and 7 with the lower dosage, but significantly increased from day 1 to day 7 after the higher dosage. This paralleled inhibition of serum TxB2 levels (99% vs 95% average inhibition by 160 and 80 mg/day) and of urinary excretion of thromboxane metabolite (77% vs 61% average inhibition by 160 and 80 mg/day), without altering the excretion of prostacyclin metabolite. Conclusions: Inhibition of serum TxB2 generation and of thromboxane metabolite urinary excretion by the lower dosage of aspirin, although substantial, still appeared incomplete. The small but significant further increase of serum TxB2 inhibition by the higher dosage was accompanied by an even greater inhibition of urinary excretion. We suggest that in some instances this difference would translate into a greater clinical benefit with the higher aspirin dosage. Our findings may also contribute to better definition of the recent concept of ‘aspirin resistance’.

Age- And Sex-Related Variations in Platelet Count in Italy: A Proposal of Reference Ranges Based on 40987 Subjects' Data

Background and Objectives Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150–400×109 platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. Methods We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. Results Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×109/L in children (176–452), adult men (141–362), adult women (156–405), old men (122–350) and, old women (140–379). Moreover, we calculated an “extended” reference interval that takes into account the differences in platelet count observed in different geographic areas. Conclusions The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy.