Nicola P. Bondonno

Apple intake is inversely associated with all-cause and disease-specific mortality in elderly women

Higher fruit intake is associated with lower risk of all-cause and disease-specific mortality. However, data on individual fruits are limited, and the generalisability of these findings to the elderly remains uncertain. The objective of this study was to examine the association of apple intake with all-cause and disease-specific mortality over 15 years in a cohort of women aged over 70 years. Secondary analyses explored relationships of other fruits with mortality outcomes. Usual fruit intake was assessed in 1456 women using a FFQ. Incidence of all-cause and disease-specific mortality over 15 years was determined through the Western Australian Hospital Morbidity Data system. Cox regression was used to determine the hazard ratios (HR) for mortality. During 15 years of follow-up, 607 (41·7%) women died from any cause. In the multivariable-adjusted analysis, the HR for all-cause mortality was 0·89 (95% CI 0·81, 0·97) per sd (53 g/d) increase in apple intake, HR 0·80 (95% CI 0·65, 0·98) for consumption of 5-100 g/d and HR 0·65 (95% CI 0·48, 0·89) for consumption of >100 g/d (an apple a day), compared with apple intake of <5 g/d (P for trend=0·03). Our analysis also found that higher apple intake was associated with lower risk for cancer mortality, and that higher total fruit and banana intakes were associated lower risk of CVD mortality (P<0·05). Our results support the view that regular apple consumption may contribute to lower risk of mortality.

The Efficacy of Quercetin in Cardiovascular Health

Cardiovascular disease is a major cause of death worldwide despite the majority of its risk factors being preventable and treatable. The results of numerous epidemiological studies suggest that a diet rich in fruits and vegetables affords protection against CVD, and this may be attributed, in part, to the flavonoid quercetin. The aims of this review are to summarise the current knowledge on the bioavailability and metabolism of quercetin as well as discuss the current evidence behind the potential mechanisms by which quercetin exerts its cardioprotective effects. This review summarises key human studies administering quercetin that have been published to date. Although interesting results have been seen in animal and cell culture studies, in general, these have not been replicated in human trials. Several studies have, however, shown that quercetin can reduce blood pressure in hypertensive patients. The exact mechanisms are yet to be elucidated. Further studies are required to investigate the use of quercetin as a cardioprotective treatment, in particular long-term and dose–response studies.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study

BACKGROUND Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. OBJECTIVES We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. DESIGN A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. RESULTS Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. CONCLUSION From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550.

Fruit Intake and Abdominal Aortic Calcification in Elderly Women: A Prospective Cohort Study

Cardiovascular disease (CVD) is the leading cause of death worldwide. There is a consistent inverse relationship between fruit intake with CVD events and mortality in cross-sectional and prospective observational studies, but the relationship of fruit intake with measurements of atherosclerosis in humans is less clear. Nutritional effects on abdominal aortic calcification (AAC), a marker for subclinical intimal and medial atherosclerotic vascular disease, have not been studied previously. The aim of this study was to examine the cross-sectional relationship of total and individual fruit (apple, pear, orange and other citrus, and banana) intake with AAC, scored between 0 and 24. The current study assessed baseline data for a cohort of 1052 women over 70 years of age who completed both a food frequency questionnaire assessing fruit intake, and underwent AAC measurement using dual energy X-ray absorptiometry. AAC scores were significantly negatively correlated with total fruit and apple intakes (p < 0.05), but not with pear, orange or banana intakes (p > 0.25). In multivariable-adjusted logistic regression, each standard deviation (SD; 50 g/day) increase in apple intake was associated with a 24% lower odds of having severe AAC (AAC score >5) (odd ratio OR): 0.76 (0.62, 0.93), p = 0.009). Total and other individual fruit intake were not associated with increased odds of having severe AAC. Apple but not total or other fruit intake is independently negatively associated with AAC in older women.

Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE-/- mouse fed a high fat diet

BACKGROUND Nitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO. AIM To determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE-/- mouse fed a high fat diet (HFD). METHODS AND RESULTS ApoE-/- fed a HFD were randomized to receive (i) high nitrate (10mmol/kg/day, n=12), (ii) moderate nitrate (1mmol/kg/day, n=8), (iii) low nitrate (0.1mmol/kg/day, n=8), or (iv) sodium chloride supplemented drinking water (control, n=10) for 10 weeks. A group of C57BL6 mice (n=6) received regular water and served as a healthy reference group. At 10 weeks, ACh-induced vessel relaxation was significantly impaired in ApoE-/- mice versus C57BL6. Mice supplemented with low or moderate nitrate showed significant improvements in ACh-induced vessel relaxation compared to ApoE-/- mice given the high nitrate or sodium chloride. Plaque collagen expression was increased and lipid deposition reduced following supplementation with low or moderate nitrate compared to sodium chloride, reflecting increased plaque stability with nitrate supplementation. Plasma nitrate and nitrite levels were significantly increased in all three groups fed the nitrate-supplemented water. CONCLUSION Low and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE-/- mice fed a HFD.

Cardiovascular health benefits of specific vegetable types: A narrative review

Adequate vegetable consumption is one of the cornerstones of a healthy diet. The recommendation to increase vegetable intake is part of most dietary guidelines. Despite widespread and long-running public health messages to increase vegetable intake, similar to other countries worldwide, less than 1 in 10 adult Australians manage to meet target advice. Dietary guidelines are predominantly based on studies linking diets high in vegetables with lower risk of chronic diseases. Identifying vegetables with the strongest health benefits and incorporating these into dietary recommendations may enhance public health initiatives around vegetable intake. These enhanced public health initiatives would be targeted at reducing the risk of chronic diseases, such as cardiovascular diseases (CVD). Specific vegetable types contain high levels of particular nutrients and phytochemicals linked with cardiovascular health benefits. However, it is not clear if increasing intake of these specific vegetable types will result in larger benefits on risk of chronic diseases. This review presents an overview of the evidence for the relationships of specific types of vegetables, including leafy green, cruciferous, allium, yellow-orange-red and legumes, with subclinical and clinical CVD outcomes in observational epidemiological studies.

Dietary inflammatory index in relation to sub-clinical atherosclerosis and atherosclerotic vascular disease mortality in older women

Arterial wall thickening, stimulated by low-grade systemic inflammation, underlies many cardiovascular events. As diet is a significant moderator of systemic inflammation, the dietary inflammatory index (DIITM) has recently been devised to assess the overall inflammatory potential of an individuals diet. The primary objective of this study was to assess the association of the DII with common carotid artery-intima-media thickness (CCA-IMT) and carotid plaques. To substantiate the clinical importance of these findings we assessed the relationship of DII score with atherosclerotic vascular disease (ASVD)-related mortality, ischaemic cerebrovascular disease (CVA)-related mortality and ischaemic heart disease (IHD)-related mortality more. The study was conducted in Western Australian women aged over 70 years (n 1304). Dietary data derived from a validated FFQ (completed at baseline) were used to calculate a DII score for each individual. In multivariable-adjusted models, DII scores were associated with sub-clinical atherosclerosis: a 1 sd (2·13 units) higher DII score was associated with a 0·013-mm higher mean CCA-IMT (P=0·016) and a 0·016-mm higher maximum CCA-IMT (P=0·008), measured at 36 months. No relationship was seen between DII score and carotid plaque severity. There were 269 deaths during follow-up. High DII scores were positively associated with ASVD-related death (per sd, hazard ratio (HR): 1·36; 95 % CI 1·15, 1·60), CVA-related death (per sd, HR: 1·30; 95 % CI 1·00, 1·69) and IHD-related death (per sd, HR: 1·40; 95 % CI 1·13, 1·75). These results support the hypothesis that a pro-inflammatory diet increases systemic inflammation leading to development and progression of atherosclerosis and eventual ASVD-related death.

Nitrate, the oral microbiome, and cardiovascular health: a systematic literature review of human and animal studies

Background Dietary nitrate is an important source of nitric oxide (NO), a molecule critical for cardiovascular health. Nitrate is sequentially reduced to NO through an enterosalivary nitrate-nitrite-NO pathway that involves the oral microbiome. This pathway is considered an important adjunct pathway to the classical l-arginine-NO synthase pathway. Objective The objective of this study was to systematically assess the evidence for dietary nitrate intake and improved cardiovascular health from both human and animal studies. Design A systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by using key search terms in Medline and EMBASE databases and defined inclusion and exclusion criteria. Results Thirty-seven articles on humans and 14 articles on animals were included from 12,541 screened references. Data on the effects of dietary nitrate on blood pressure, endothelial function, ischemic reperfusion injury, arterial stiffness, platelet function, and cerebral blood flow in both human and animal models were identified. Beneficial effects of nitrate on vascular health have predominantly been observed in healthy human populations, whereas effects in populations at risk of cardiovascular disease are less clear. Few studies have investigated the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. In animal studies, there is evidence that nitrate improves blood pressure and endothelial function, particularly in animal models with reduced NO bioavailability. Nitrate dose seems to be a critical factor because there is evidence of cross-talk between the 2 pathways of NO production. Conclusions Evidence for a beneficial effect in humans at risk of cardiovascular disease is limited. Furthermore, there is a need to investigate the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. Further animal studies are required to elucidate the mechanisms behind the observed effects.

Vegetable-derived bioactive nitrate and cardiovascular health

Vegetable derived nitrate is now recognised as an important bioactive phytochemical with cardioprotective properties. Nitrate, through the recently described enterosalivary nitrate-nitrite-nitric oxide (NO) pathway, increases NO, a molecule pivotal for cardiovascular health. Clinical trials have observed that dietary nitrate has similar effects to NO when supplied exogenously. These effects include reduced blood pressure and improvements in other markers of vascular health such as endothelial function, arterial stiffness, ischemia reperfusion injury, blood flow, and platelet aggregation. Few observational studies, however, have examined dietary nitrate intake and long term cardiovascular health outcomes. This represents a significant gap in the literature. There is also a lingering concern about a possible carcinogenic effect of nitrate intake. Additionally, a number of potential factors that could impact nitrate to nitrite to NO reduction have been identified. This review will provide an overview of the evidence to date that nitrate, through its effects on endogenous NO and vascular health, is an important bioactive cardioprotective component of a diet rich in vegetables.

Cruciferous and Total Vegetable Intakes Are Inversely Associated With Subclinical Atherosclerosis in Older Adult Women

Background Dietary patterns rich in fruits and vegetables are considered to reduce atherosclerotic disease presentation and are reported to be inversely associated with subclinical measures of atherosclerosis, such as carotid artery intima‐media thickness (IMT) and plaque. However, the effect of vegetable intake alone, and relationships to specific types of vegetables containing different phytochemical profiles, is important. The aim of this study was to investigate the associations of total vegetable intake and specific vegetables grouped according to phytochemical constituents with common carotid artery IMT (CCA‐IMT) and carotid plaque severity in a cohort of older adult women (aged ≥70 years). Methods and Results Total vegetable intake was calculated at baseline (1998) using a validated food frequency questionnaire. Vegetable types included cruciferous, allium, yellow/orange/red, leafy green, and legumes. In 2001, CCA‐IMT (n=954) and carotid focal plaque (n=968) were assessed using high‐resolution B‐mode carotid ultrasonography. Mean (SD) total vegetable intake was 199.9 (78.0) g/d. Women consuming ≥3 servings of vegetables each day had ≈4.6% to 5.0% lower mean CCA‐IMT (P=0.014) and maximum CCA‐IMT (P=0.004) compared with participants consuming <2 servings of vegetables. For each 10 g/d higher in cruciferous vegetable intake, there was an associated 0.006 mm (0.8%) lower mean CCA‐IMT (P<0.01) and 0.007 mm (0.8%) lower maximum CCA‐IMT (P<0.01). Other vegetable types were not associated with CCA‐IMT (P>0.05). No associations were observed between vegetables and plaque severity (P>0.05). Conclusions Increasing vegetables in the diet with a focus on consuming cruciferous vegetables may have benefits for the prevention of subclinical atherosclerosis in older adult women. Clinical Trial Registration URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615000750583.