Francesco Sofi

Adherence to Mediterranean diet and health status: meta-analysis

Objective To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting. Design Meta-analysis of prospective cohort studies. Data sources English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574 299 subjects followed for a time ranging from three to 18 years were included. Results The cumulative analysis among eight cohorts (514 816 subjects and 33 576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson’s disease and Alzheimer’s disease (0.87, 0.80 to 0.96). Conclusions Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson’s disease and Alzheimer’s disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.

Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis,

BACKGROUND The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.

Physical activity and risk of cognitive decline: a meta-analysis of prospective studies

Abstract.  Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C (Centro S. Maria agli Ulivi, Onlus IRCCS; Thrombosis Centre, University of Florence; Azienda Ospedaliero‐Universitaria Careggi, Florence, Italy) Physical activity and risk of cognitive decline: a meta‐analysis of prospective studies. J Intern Med 2011; 269: 107–117.

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study

Background  Recent studies suggest a role of n‐3 long‐chain polyunsaturated fatty acids (n‐3 PUFA) as peroxisome proliferator‐activated receptor‐α ligands in improving non‐alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.

Physical activity during leisure time and primary prevention of coronary heart disease: an updated meta-analysis of cohort studies

Background A vast body of evidence during the last decades has shown the clear preventive role of physical activity in cardiovascular disease. The real magnitude of the association between physical activity during leisure time (LTPA) and primary prevention of coronary heart disease (CHD) has, however, not been completely defined. Design Meta-analysis of prospective cohort studies. Methods Studies were included if they reported relative risks and their corresponding 95% confidence intervals (CI), for categories of LTPA in relation to CHD. The LTPA categories of the selected studies were grouped into three levels of intensity: high, moderate and low. The high level of physical activity was determined, to obtain a level of intensity attainable by the general population. Results Data were available for 26 studies, incorporating 513472 individuals (20666 CHD events), followed up for 4–25 years. Under a random-effects model, the overall analysis showed that individuals who reported performing a high level of LTPA had significant protection against CHD [relative risk 0.73 (95% CI 0.66–0.80), P < 0.00001]. A similar significant protection against CHD, for individuals who practised a moderate level of LTPA, has been also demonstrated [relative risk 0.88 (95% CI 0.83–0.93), P < 0.0001]. Conclusions The current meta-analysis reports significant protection against the occurrence of CHD resulting from moderate-to-high levels of physical activity. These results strengthen the recommendations of guidelines that indicate the protective effect against cardiovascular disease of physical activity profiles that are attainable by ordinary people.

Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score.

OBJECTIVE To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet. DESIGN We conducted a comprehensive literature search through all electronic databases up to June 2013. SETTING Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained. SUBJECTS The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses. RESULTS A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet. CONCLUSIONS The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.

Clopidogrel non-responsiveness and risk of cardiovascular morbidity: an updated meta-analysis

We performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients followed for a time ranging from 14 days to one year, were included. The cumulative analysis reported that residual platelet reactivity despite clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a consistent heterogeneity of the model and evidenced a significant risk of publication bias, so were excluded from the analysis. This exclusion, however, did not influence the overall result, by confirming the increased risk of cardiovascular recurrences for patients with a poor response to clopidogrel treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta-analysis documents a significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events, so suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.

Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations

The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.

Insomnia and risk of cardiovascular disease: a meta-analysis

Objective: Increasing evidence suggests an association between insomnia and cardiovascular disease. We performed a systematic review with meta-analysis of all the available prospective studies that investigated the association between insomnia and risk of developing and/or dying from cardiovascular disease. Design: Systematic review and meta-analysis of prospective cohort studies. Methods: We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to December 2011. Studies were included if they were prospective, had assessment of insomnia or sleep complaints at baseline, evaluated subjects free of cardiovascular disease at baseline and measured the association between insomnia and risk of developing and/or dying from cardiovascular disease. Results: After the review process 13 prospective studies were included in the final analysis. These studies included 122,501 subjects followed for a time ranging from three to 20 years. A total of 6332 cardiovascular events occurred during the follow-up. Insomnia was assessed through questionnaire and defined as either difficulty of initiating or maintaining sleep or presence of restless, disturbed nights. The cumulative analysis for all the studies under a random-effects model showed that insomnia determined an increased risk (+45%) of developing or dying from cardiovascular disease during the follow-up (relative risk 1.45, 95% confidence interval 1.29–1.62; p < 0.00001), with no evidence of heterogeneity across the studies (I2: 19%; p = 0.14). Conclusion: Insomnia is associated with an increased risk of developing and/or dying from cardiovascular disease.

Cytochrome P450 2C19 * 2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis

Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19*2 (or 681 G>A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the *2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19*2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14–3.37); P=0.02). When studies evaluating stent thrombosis (n=4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23–6.54); P=0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19*2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.