on behalf of the GISSI-Prevenzione InvestigatorsBackground-Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (Ͻ3 months) myocardial infarction. Methods and Results-In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; Pϭ0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; Pϭ0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. Conclusions-The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.

Background: The GISSI Heart Failure project is a large-scale, randomized, double-blind study designed to investigate the effects of n-3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure. Methods and results: Patients with New York Heart Association classes II to IV heart failure, already receiving optimized recommended therapy, will be recruited in a nation-wide network of more than 300 cardiology and internal medicine services to be randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or the corresponding placebo. Patients with no clear indication or contraindication to cholesterollowering therapy will be further randomized to receive low-dose rosuvastatin (10 mg daily) or placebo. According to data available in heart failure registries, it is expected that 70% of the patients will be suitable to enter both components of the trial, which assume the same coprimary endpoints: (a) 15% reduction of all-cause mortality and (b) 20% reduction of all-cause mortality or cardiovascular hospitalizations. The trial is event-driven and will continue either until at least 1252 deaths have been recorded or a reduction of all-cause mortality will satisfy the significance boundaries, which have been established to stop the study. The recruitment of the planned sample size of approximately 7000 patients randomized in the n-3 PUFA trial is expected to be completed within 18 months from the trial start. As of February 29, 2004, 4624 heart failure patients have been included in the trial. Conclusion: The GISSI-HF project, with its protocol articulated into two independent randomization schemes, has the aim and the power to verify the hypothesis that n-3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure.

The assessment of arterial stiffness, a common feature of ageing, exacerbated by many common disorders such as hypertension, diabetes mellitus, or renal diseases, has become an attractive tool for identifying structural and functional abnormalities of the arteries in the preclinical stages of the atherosclerotic disease. Arterial stiffness has been recognized as an important pathophysiological determinant of systolic blood pressure and pulse pressure increases and therefore the cause of cardiovascular complications, demonstrating also an independent predictive value for cardiovascular events. Although there are many techniques and indices currently available, their large clinical application is limited by a lack of standardization, with important difficulties when one try effectively to measure, quantify, and compare. Moreover, information on the 'heart-vessel coupling disease', in which combined stiffness of both heart and arteries interact to limit cardiovascular performance and its possible implications in different clinical conditions, is still not well known. We overviewed main methods and indices used to estimate arterial stiffness and aimed to provide an insight into the knowledge of the ventricular-arterial coupling from the cardiologist's point of view.

Left ventricular dilation may occur even after uncomplicated AMI and may be paralleled by an improvement in LV filling. However, a baseline restrictive filling that persists at pre-discharge identifies more compromised patients at higher risk for six-month remodeling and four-year mortality.