Background Antioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action. Methods We examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged ≥ 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF2α (isoprostane F2α-III or 15-F2t-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry. Results Urinary excretion of 8-epi-PGF2α [pg/mg creatinine, median (range)] was 141 (67–498) in treated and 148 (76–561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that vitamin E had no significant effect on this biomarker. Levels of 8-epi-PGF2α were in the normal range for most subjects, except smokers and those with uncontrolled blood pressure or hyperglycemia. Conclusions Prolonged vitamin E supplementation did not reduce lipid peroxidation in subjects with major cardiovascular risk factors. The observation that the rate of lipid peroxidation was near normal in a large proportion of subjects may help explain why vitamin E was not effective as an antioxidant in the PPP study and was ineffective for CVD prevention in large scale trials.

Large scale clinical trials demonstrate significant reductions in cardiovascular event rates with statin therapy. The observed benefit of statin therapy, however, may be larger in these trials than that expected on the basis of lipid lowering alone. Emerging evidence from both clinical trials and basic science studies suggest that statins have anti-inflammatory properties, which may additionally lead to clinical efficacy. Measurement of markers of inflammation such as high sensitivity C-reactive protein in addition to lipid parameters may help identify those patients who will benefit most from statin therapy.

Statins reduce mortality of patients with coronary artery disease (CAD). However, by protocol, trials have excluded patients with chronic heart failure. Since the prevalent etiology of heart failure is CAD, preventing CAD may prevent heart failure progression. Statins may have other beneficial effects besides cholesterol lowering, such as anti-inflammatory properties and improvement of endothelial function. On the contrary, high levels of cholesterol can be beneficial in heart failure patients on the basis of the ability of serum lipoproteins to modulate inflammatory response. Furthermore, statins affecting mitochondrial function can have a deleterious effect on skeletal or cardiac muscles. Despite all these conflicting data, there is no evidence from trials on the effects of statins in patients with heart failure. For this reason, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) investigators planned a controlled trial testing the effect of statins in patients with heart failure of different etiology.

Of the associations between dietary elements and coronary artery disease (CAD), the greatest body of evidence deals with the beneficial effect of reducing the dietary intake of saturated fatty acids and cholesterol. Furthermore, it is well established, on the basis of convincing evidence, that reduction in serum total cholesterol results in reduction in coronary morbidity and mortality, as well as in regression of other atherosclerotic manifestations.In fact, dietary intervention studies revealed that it is possible to reduce the incidence of coronary death and nonfatal myocardial infarction, as well as manifestations of atherosclerosis in cerebral and peripheral arteries, by reducing dietary intake of saturated fat and cholesterol. In two recently reported dietary interventions the incidence of coronary events, especially coronary mortality, and total mortality were reduced by increased intake of n-3 long-chain polyunsaturated fatty acids and by a modification of the diet toward a Mediterranean-type diet (rich in α-linolenic acid. In addition to those findings, the potential efficacy of the dietary newcomers phytostanol and phytosterol esters on reducing coronary incidence is discussed in the present review.

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. Particulate matter-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/-) mice which possess decreased anti-oxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/- mouse aortas, and relaxation was significantly reduced in young SOD2+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/- mice. Data demonstrate that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of anti-oxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/- mice. This dataset is associated with the following publication: Carter, J., N. Madamanchi , G. Stouffer, M. Runge, W. Cascio, and H. Tong. Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2 Deficient Murine Aortic Rings. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 81(5): 106-115, (2018).

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. Particulate matter-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/-) mice which possess decreased anti-oxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/- mouse aortas, and relaxation was significantly reduced in young SOD2+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/- mice. Data demonstrate that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of anti-oxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/- mice. This dataset is associated with the following publication: Carter, J., N. Madamanchi , G. Stouffer, M. Runge, W. Cascio, and H. Tong. Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2 Deficient Murine Aortic Rings. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 81(5): 106-115, (2018).

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. Particulate matter-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/-) mice which possess decreased anti-oxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/- mouse aortas, and relaxation was significantly reduced in young SOD2+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/- mice. Data demonstrate that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of anti-oxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/- mice. This dataset is associated with the following publication: Carter, J., N. Madamanchi , G. Stouffer, M. Runge, W. Cascio, and H. Tong. Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2 Deficient Murine Aortic Rings. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 81(5): 106-115, (2018).

Treatment to prevent progression of heart failure has been targeted to reverse the consequences of heart failure and to a lesser extent the cause – the atherosclerotic plaque itself. Less than 50% of patients with heart failure are treated with lipid intervention. Heart failure (New York Heart Association [NYHA] functional classes I and II) is associated with an increase in low-density lipoproteins (LDL) and triglycerides while high-density lipoproteins (HDL) is lowered. In NYHA class IV, cholesterol is reduced due to depressed production in the liver. Although lipoproteins, especially LDL and HDL, may have some protective effect in binding and neutralising endotoxins released from the intestine during terminal heart failure, observational studies in patients with heart failure strongly suggest that lipid modification with statins may reduce progression of heart failure as well as reducing heart failure mortality.

The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study was the first trial to assess whether statins might be of clinical benefit in those with recently unstable coronary disease. MIRACL found that high-dose atorvastatin was safe and reduced the incidence of the composite endpoint, death, non-fatal myocardial infarction, resuscitated sudden cardiac death or emergent rehospitalization for recurrent ischemia at 16 weeks when compared with placebo. Despite a number of important study limitations, MIRACL's findings and the prior observation that inpatient initiation of lipid-lowering therapy is associated with higher rates of subsequent utilization, suggest that it is prudent to begin statin therapy when patients present with an acute coronary syndrome.