Pulmonary vascular dysfunction in refractory acute respiratory distress syndrome before veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary vascular dysfunction has been described in patients with acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a well-established treatment for these patients. We hypothesized that severe pulmonary vascular dysfunction and cor pulmonale identified by echocardiography before cannulation in these patients were associated with worse survival. METHODS: Echocardiography was used to identify pulmonary hypertension in 21 patients with refractory ARDS just before ECMO implantation. Survival was compared for those with and without cor pulmonale. RESULTS: In our series, the overall mortality rate was 57.1% (12/21). Echocardiographic exams were transthoracic in 5 patients (23.8%), transesophageal in 4 patients (19%), and both (transthoracic and transesophageal) in the remaining 12 patients (57.1%). In our series, six patients (28.5%) showed LV dysfunction. Acute cor pulmonale was detectable in 2 patients (9.5%), while the remaining 19 patients showed moderate pulmonary dysfunction. Survivors had a higher pre-cannulation LV ejection fraction (EF) (P = 0.02) and tricuspid annular plane excursion (P = 0.04), and lower peak systolic pulmonary artery pressures (P = 0.02). CONCLUSIONS: In patients with refractory ARDS immediately before ECMO implantation, the prevalence of acute cor pulmonale is low (9.5%). Survival is associated with higher LVEF and lower systolic pulmonary arterial pressure. These findings support the idea that echocardiographic assessment of pulmonary artery pressure in patients with refractory ARDS before VV-ECMO implantation may have value for risk-stratification.

Surgical RF ablation of atrial fibrillation in patients undergoing mitral valve repair for Barlow disease.

OBJECTIVES: At present, limited experience exists on the treatment of atrial fibrillation (AF) in patients undergoing mitral valve repair (MVR) for Barlow disease. The aim of this investigation was to prospectively evaluate the radiofrequency ablation of AF in patients undergoing MVR for severe regurgitation due to Barlow disease. METHODS: From January 1, 2007 to December 31, 2010, out of 85 consecutive patients with Barlow disease, 27 with AF underwent RF ablation associated with MVR. They were examined every 4 months in the first year after surgery and thereafter twice yearly. RESULTS: At follow-up, AF was observed in 4/25 (16.0%). NYHA (New York Heart Association) functional class improved significantly, with no patients in class III or IV (before surgery, 81.5% had been). Otherwise, among 58 patients in sinus rhythm, 6 (11%) developed AF during follow-up. No clinical or echocardiographic predictive factor was found in this subgroup. CONCLUSIONS: Results from our investigation suggest that radiofrequency ablation of AF in patients with Barlow disease undergoing MVR for severe regurgitation is effective and should be considered in every patient with Barlow disease and AF undergoing valve surgical repair.

Impact of age on the prognostic value of body mass index in ST-Elevation myocardial infarction.

BACKGROUND AND AIM: No data are so far available on the impact of age and obesity in ST-elevation myocardial infarction (STEMI) submitted to percutaneous coronary intervention (PCI). METHODS AND RESULTS: We assessed the impact of age on the prognostic value of body mass index (BMI) in 1268 consecutive STEMI patients admitted to our Intensive Cardiac Care Unit (ICCU). BMI categories were as follows: 37 "lean" patients (37/1268, 2.9%), 403 "normal" patients (403/1268, 31.8%), 656 "overweight" patients (656/1268, 51.7%), 172 "obese" patients (172/1268, 13.6%). Among patients aged <75 years, as BMI increased, the number of males and diabetic patients significantly increased (p < 0.001 and p = 0.004, respectively). Among STEMI patients aged ≥75 years, lean patients showed a higher in-ICCU mortality in respect to the other BMI categories but this did not reach statistical significance. BMI was an independent predictor of In-ICCU mortality in the whole population (lean vs. "normal": OR 3.47, 95%CI 1.08-11.14, p = 0.036) and it was associated with long term mortality only in patients <75 years since lean and overweight patients showed lower survival rate (lean vs. "normal": HR 9.25, 95%CI 3.09-27.63, p < 0.001; overweight vs. "normal": OR 2.10; 95%CI 1.04-4.23, p = 0.039). CONCLUSIONS: In our series, underweight is associated with the highest mortality across all age subgroups, while only in patients <75 years, overweight patients showed increased in-hospital mortality rate and a poorer long term survival rate. According to our data, the "so called obesity paradox" should be probably age-contextualized.

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

OBJECTIVE: The relationship between physical activity and cognitive function is intriguing but controversial. We performed a systematic meta-analysis of all the available prospective studies that investigated the association between physical activity and risk of cognitive decline in nondemented subjects. 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 January 2010. Studies were included if they analysed prospectively the association between physical activity and cognitive decline in nondemented subjects. RESULTS: After the review process, 15 prospective studies (12 cohorts) were included in the final analysis. These studies included 33,816 nondemented subjects followed for 1-12 years. A total of 3210 patients showed cognitive decline during the follow-up. The cumulative analysis for all the studies under a random-effects model showed that subjects who performed a high level of physical activity were significantly protected (-38%) against cognitive decline during the follow-up (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54-0.70; P < 0.00001). Furthermore, even analysis of low-to-moderate level exercise also showed a significant protection (-35%) against cognitive impairment (HR 0.65, 95% CI 0.57-0.75; P < 0.00001). CONCLUSION: This is the first meta-analysis to evaluate the role of physical activity on cognitive decline amongst nondemented subjects. The present results suggest a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.

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.

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome.

BACKGROUND AND AIM: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients. METHODS AND RESULTS: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [ß (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not -786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the -786C/894G/4a and -786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus. CONCLUSIONS: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.

Emerging drugs for acute myocardial infarction.

IMPORTANCE OF THE FIELD: The present review is aimed at going over the pharmacological profile (and the clinical impact) of the emerging drugs involved in the management of patients with ST-elevation myocardial infarction (STEMI) in order to provide the cardiologists who deal with these patients in the early phase with the most recent evidence on this topic. AREAS COVERED IN THIS REVIEW: Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the treatment of STEMI patients undergoing primary percutaneous coronary intervention (PCI). The main issues that clinicians have to deal with are represented by balancing thrombotic and bleeding risks. In tailoring therapy, variables such as age, sex and previous disease should be taken into account, as well as ongoing complications (such as acute renal failure) that could affect hemostasis. Despite the well-established clinical benefits of antiplatelet agents, questions remain, mainly surrounding potential for variable platelet response, which are strictly related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such as obesity, diabetes mellitus, and inflammation) and genetic determinants. WHAT THE READER WILL GAIN: In their daily practice, cardiologists cannot abstract from the knowledge and updating on the ongoing research fields as well as the newly developed drugs, which they should frame in the very patient in the attempt to the develop a personalized medical strategy. These include also the pharmacological option(s) in the treatment of the reperfusion injury, the metabolic aspects and the stem cell therapy. TAKE HOME MASSAGE: In our opinion, the goal of ongoing research on the pharmacological approach to STEMI patients is a personalized medical strategy that relies on critical clinicians who merge newly developed acquisitions on this topic and a more complete, systemic and critical approach to the patient.

Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study.

BACKGROUND AND AIM: Some studies recently reported a favourable effect for cis-9, trans-11 conjugated linoleic acid (CLA) on plasma lipoprotein profile of healthy subjects. Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep's milk naturally rich in CLA on several atherosclerotic biomarkers, in comparison with a commercially available cheese. METHODS AND RESULTS: Ten subjects (6 F; 4 M) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA (intervention period) and for the same period a diet containing a commercially available cheese of the same quantity (placebo period). Consumption of the dairy product naturally rich in cis-9, trans-11 CLA determined a significant (p<0.05) reduction in inflammatory parameters such as interleukin-6 (pre: 8.08+/-1.57 vs. post: 4.58+/-0.94 pg/mL), interleukin-8 (pre: 45.02+/-5.82 vs. post: 28.59+/-2.64 pg/mL), and tumour necrosis factor-alpha (pre: 53.58+/-25.67 vs. post: 32.09+/-17.42 pg/mL) whereas no significant differences in the placebo period were observed. With regard to haemorheological parameters, the test period significantly ameliorated erythrocytes' filtration rate (pre: 7.61+/-0.71% vs. post: 9.12+/-0.97%; p=0.03) with respect to the placebo period. Moreover, a reduction in the extent of platelet aggregation, induced by arachidonic acid [pre: 87.8+/-1.76% vs. post: 77.7+/-3.56%; p=0.04] was observed during the test period in comparison with the placebo period. CONCLUSIONS: Dietary short-term intake of the tested dairy product naturally rich in cis-9, trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers.

The value of lung ultrasound monitoring in H1N1 acute respiratory distress syndrome.

We present the case of a healthy young male who developed acute respiratory failure as a result of infection with influenza A/H1N1 of swine-origin and in whom ventilatory support was optimised and recovery of lung function was monitored by the use of sequential chest ultrasound examinations. The potential pivotal role of bedside lung ultrasonography in H1N1-induced respiratory failure is discussed.

The concept of risk in medicine: historical and epistemological reflections.

The concept of risk in medicine varies according to different health settings and different times. At present, risk is considered, in the cardiovascular area, the probability of developing a clinical event through time computed on the basis of the quantification of the presence and of the interaction of different diseases and/or risk factors. The definition of risk factors in the biomedical field is here documented through time to show how recent clinical-epidemiological elements have been achieved. In the twentieth century many epistemological and methodological objectives have been attained with regard to the theoretical idea of risk and to the practical tools useful to modify it, and the example of the management of diabetes is furnished as documentation of this progress. Nonetheless, correct risk evaluation continues to remain a formidable challenge in the health scenario.

SPREAD Italian Guidelines for stroke. Indications for carotid endarterectomy and stenting.

This multidisciplinary guideline provides an overview of the current evidence on the benefits obtained by endoarterectomy and stenting for the surgical treatment of patients with symptomatic and asymptomatic carotid stenosis. A hundred forty-six authors, 37 Italian scientific societies and two Italian patients' associations participated in drafting the Stroke Prevention and Educational Awareness Diffusion (SPREAD) document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of this document, the main trials on carotid endoarterectomy and stenting were critically reviewed following The Scottish Intercollegiate Guideline Network Oxford Centre for Evidence-Based Medicine methodology in order to formulate recommendations and syntheses for these procedures. The final document was peer reviewed and approved by all the participants. Recommendations and syntheses are presented for the referral of patients to either carotid endoarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic, on the presence of various risk factors such as degree of arterial narrowing, and on concomitant pathology (cardiopathy and acute stroke).

The preventive and therapeutic impact of antiplatelet agents: past and present.

Already more than two thousands years ago the Greek physician Hippocrates (V-IV century B.C.) used the extracts of the willow bark to fight fever. At the end of the eighteen hundreds the German chemist Felix Hoffmann obtained acetylsalicylic acid in stable and pure form, and from then on Aspirin (where A is the abbreviation of acetyl and Spir stands for Spirsaure, the German name of salicylic acid) has had enormous diffusion. In 1953 Lawrence Craven reported that he had successfully prescribed aspirin to hundreds of adult male patients for the non-specific prophylaxis of coronary thrombosis. Aspirin is now one of the most well-known drugs in the world, and in the last decades a large body of scientific evidence has appeared with regard to the preventive and therapeutic effects of aspirin and those of other antiplatelet agents. In fact, antiplatelet agents constitute a cornerstone in current pharmacological treatment and prophylaxis. Among the most interesting recent and beneficial areas of impact of aspirin and of other antiplatelet drugs, there are those of stroke and of coronary artery disease, and today targeted pharmacological and non-pharmacological interventions should be carefully combined to deal, preventively and therapeutically, with the cardiovascular epidemic.

Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials.

AIM: The aim of this meta-analysis of randomized clinical trials (RCT) was to assess whether pioglitazone is also associated with increased cardiovascular risk, as recently reported for rosiglitazone. METHODS: RCT of pioglitazone were retrieved from Medline (any date up to 31 August 2007; English language only). Unpublished RCT were identified through http://www.clinicaltrials.gov or http://www.fda.gov websites, and results on cardiovascular outcomes were retrieved from investigators and/or sponsors, whenever possible. RCT were included in meta-analysis if pioglitazone was compared with other treatments (placebo, active comparators or no treatment) for at least 4 weeks. Ninety-four trials, 10 of which were unpublished, were retrieved; those included in the analysis, which excluded PROspective PioglitAzone Clinical Trial In MacroVascular Events (PROACTIVE), enrolled 11 268 and 9912 patients in the pioglitazone and comparator groups respectively. Data for analysis, extracted independently by two observers, included all-cause and cardiovascular mortality and incidence of non-fatal coronary events and heart failure. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% confidence interval. RESULTS: Pioglitazone was associated with reduced all-cause mortality [OR 0.30 (0.14-0.63); p < 0.05], with no relevant effect on non-fatal coronary events. The observed increase in incidence of non-fatal heart failure was not statistically significant [OR 1.38 (0.90-2.12)]. CONCLUSION: The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.

Doctor-patient communication: a historical overview.

Doctor-patient communication is an issue that is attracting more and more attention within the international scientific community, stimulating an interest involving many different health contexts, from academic to medico-legal ones. In the academic setting, the insertion of health communication courses into the curriculum has been a recent renovation, given that in the past such training was not considered a necessary formative step. In the medico-legal scenario, among the main causes of legal action is an incorrect, incomplete or non-existent transmission of information. Doctor-patient communication is therefore an extremely up-to-date topic, the problematic of which may already be discerned in Western medicine in the so-called Hippocratic Oath. In this paper the historical roots and the evolution through time of doctor-patient communication are discussed, together with the description of the predominant models of communication of the past (the physician-centred and the disease-centred approaches) and of the present (the patient-centred and the person-centred paradigms). Nowadays complete, correct and comprehensible communication is a primary exigency for the physician, for the patient/person and for all the organizational levels of the sanitary system. Every physician and, more in general, every health operator, must therefore learn to communicate effectively in the course of his/her medical training, and must continually refine this capacity during his/her professional career.

Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients.

BACKGROUND: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. OBJECTIVES AND METHODS: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5'-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. RESULTS: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. CONCLUSIONS: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.

Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: the achieve cholesterol targets fast with atorvastatin stratified titration (ACTFAST) study.

AIMS: To investigate whether selecting the starting dose of atorvastatin according to baseline and target (<2.6 mmol/L) LDL-cholesterol (LDL-C) values would allow high-risk subjects to achieve target LDL-C concentration within 12 weeks, with the initial dose or a single uptitration. METHODS AND RESULTS: Twelve-week, prospective, open-label trial that enrolled 2117 high-risk subjects (statin-free [SF] or statin-treated [ST]). Subjects with LDL-C >2.6 mmol/L (100mg/dL) but

Relationship between physical activity and cardiovascular disease. Selected historical highlights.

The full awareness that physical exercise represents a form of prevention and therapy for cardiovascular diseases is rather recent, considering that the discovery of blood circulation dates back to the 17th century and that the definition of major cardiovascular risk factors is an acquisition of the 20th century. In this paper a historical review has been undertaken so as to evidence major selected highlights of cardiovascular knowledge applied to physical activity from antiquity to the present day. Despite of the fact that the role of physical activity for the sake of a good body equilibrium is an ancient concept, as documented by the recurrent term ''exercise'' in the works of Hippocrates, only about 70 years have passed from the time when, in the '30s, myocardial infarction patients were strictly advised to observe a period of bed rest of at least 6 weeks; less than a century has passed since the so-called ''chair therapy'' constituted the cornerstone of the therapy of the cardiovascular patient. In the '40s and the '50s a certain amount of attentive mobilization proved to be beneficial, given that it was associated with a remarkable reduction of thromboembolic risk. In the '70s an increasing amount of clinical literature documented that even healthy subjects, remaining in bed for a long period, showed relatively rapidly signs of de-conditioning. In 1973 Kavanagh et al. demonstrated that the patients included in cardiac rehabilitation showed an improvement in their physical work capacity, an increase in their global cardiovascular function and went back more quickly and safely to their work environment, as compared with cardiac patients not performing rehabilitative physical exercise. The studies performed in the '70s provided the bases of modern cardiovascular rehabilitation, a multidimensional and integrated approach, one of whose pillars is structured physical activity.

The concept of normality through history: a didactic review of features related to philosophy, statistics and medicine.

Normality characterises in medicine any possible qualitative or quantitative situation whose absence implies an illness or a state of abnormality. The illness concept was first a philosophical one. But the use of mathematics in the study of biological events, which began with Galton (1822-1911) and with Pearson (1857-1936), changed the frame of reference. In the second part of the 19th century mathematics was used to study the distribution of some biological characteristics in the evolution of the species. Around 1900, statistics became the basis for the study of the diffusion of the illnesses. Half a century later statistics made possible the transition from the description of single cases to groups of cases. Even more important is the concept of "normality" in laboratory medicine. In this field the search for the "perfect norm" was, and possibly still is, under way. The widespread use of statistics in the laboratory has allowed the definition, in a certain sense, of a new normality. This is the reason why the term "reference value" has been introduced. However, even the introduction of this new term has merely shifted the problem, and not resolved it.

Alpha-linolenic acid and cardiovascular diseases omega-3 fatty acids beyond eicosapentaenoic acid and docosahexaenoic acid.

Over the last decades, an increasing body of evidence has been accumulated on the beneficial effect of polyunsaturated fatty acids both in primary and secondary prevention of cardiovascular diseases. However, the vast majority of the studies has been performed on long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and not on their biochemical precursor, alpha-linolenic acid (ALA). Actually, ALA has some other beneficial effects apart from the known antiarrhythmic effect. In fact, ALA has a strong inhibitory effect on omega-6 metabolic pathway. An adequate daily intake of ALA shifts metabolic pathway to EPA, so favoring the formation of products with a predominant antiaggregating and vasorelaxing action, with respect to eicosanoids with a predominant thrombotic effect. Some important evidences have been raised on the association between ALA and cardiovascular mortality. Indeed, dietary ALA has been associated with a lower rate of fatal and nonfatal coronary events. Hence, major scientific associations published nutritional guidelines including a specific recommendation for ALA.