Lauren C. Blekkenhorst

Association of vegetable nitrate intake with carotid atherosclerosis and ischemic cerebrovascular disease in older women

Background and Purpose— A short-term increase in dietary nitrate (NO3−) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226). Methods— Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System. Results— Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=−0.015, P=0.002) and lower mean CCA-IMT (B=−0.012, P=0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors (P⩽0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models (P=0.02). Conclusions— Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event.

Association of dietary nitrate with atherosclerotic vascular disease mortality: A prospective cohort study of older adult women

Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality.Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality.Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors.Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean ± SD vegetable nitrate intake was 67.0 ± 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariable-adjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011].Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult women without prevalent ASVD or diabetes. These results support the concept that nitrate-rich vegetables may reduce the risk of age-related ASVD mortality. This trial was registered at www.anzctr.org.au as ACTRN12617000640303.

Development of a reference database for assessing dietary nitrate in vegetables

SCOPE Nitrate from vegetables improves vascular health with short-term intake. Whether this translates into improved long-term health outcomes has yet to be investigated. To enable reliable analysis of nitrate intake from food records, there is a strong need for a comprehensive nitrate content of vegetables database. METHODS AND RESULTS A systematic literature search (1980-2016) was performed using Medline, Agricola and Commonwealth Agricultural Bureaux abstracts databases. The nitrate content of vegetables database contains 4237 records from 255 publications with data on 178 vegetables and 22 herbs and spices. The nitrate content of individual vegetables ranged from Chinese flat cabbage (median; range: 4240; 3004-6310 mg/kg FW) to corn (median; range: 12; 5-1091 mg/kg FW). The database was applied to estimate vegetable nitrate intake using 24-h dietary recalls (24-HDRs) and food frequency questionnaires (FFQs). Significant correlations were observed between urinary nitrate excretion and 24-HDR (r = 0.4, P = 0.013), between 24-HDR and 12 month FFQs (r = 0.5, P < 0.001) as well as two 4 week FFQs administered 8 weeks apart (r = 0.86, P < 0.001). CONCLUSION This comprehensive nitrate database allows quantification of dietary nitrate from a large variety of vegetables. It can be applied to dietary records to explore the associations between nitrate intake and health outcomes in human studies.

Dietary saturated fat intake and atherosclerotic vascular disease mortality in elderly women: a prospective cohort study

BACKGROUND The reduction of saturated fatty acid (SFA) intake has been the basis of long-standing dietary recommendations. However, recent epidemiologic studies have reported conflicting evidence in the relation between SFA consumption and risk of atherosclerotic vascular disease (ASVD) mortality. OBJECTIVE We investigated the association of SFA intake with serum lipid profiles and ASVD mortality in a population-based 10-y cohort study. DESIGN At baseline (1998) 1469 women living in Perth, Western Australia, with a mean ± SD age of 75.2 ± 2.7 y had SFA intake measured by using a validated food-frequency questionnaire. Outcome data were serum lipids at baseline and ASVD deaths over 10 y (13,649 person-years of follow-up), retrieved from the Western Australian Data Linkage System. Other risk factors for ASVD were assessed and adjusted for in multivariable analyses. RESULTS ASVD deaths occurred in 9.1% (134) of participants. The highest quartile of SFA intake (>31.28 g/d) had an ~16% cumulative mortality risk compared with ~5% in the lowest quartile (<17.39 g/d) (HR: 3.07; 95% CI: 1.54, 6.11; P = 0.001). Baseline SFA intake was associated with baseline serum total and LDL cholesterol in multivariable-adjusted models (β: 0.199, SE: 0.056, P < 0.001 and β: 0.190, SE: 0.051, P < 0.001, respectively). However, baseline serum total and LDL cholesterol were not associated with ASVD mortality. CONCLUSIONS High SFA intake was associated with the risk of ASVD mortality in this population of elderly women. Although there was a strong positive association between SFA intake and LDL cholesterol, LDL cholesterol was not associated with ASVD mortality in this cohort. Nevertheless, these data support dietary advice to reduce SFA intake.

Cruciferous and allium vegetable intakes are inversely associated with 15‐year atherosclerotic vascular disease deaths in older adult women

Background Higher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality. Methods and Results The cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were ascertained from linked mortality data. During 15 years (15 947 person‐years) of follow‐up, 238 ASVD‐related deaths occurred. A 1‐serving increment of vegetable intake was associated with a 20% lower hazard of ASVD‐related death (multivariable‐adjusted hazard ratio, 0.80; 95% confidence interval, 0.69–0.94 [P=0.005]). In multivariable‐adjusted models for vegetable types, cruciferous (per 10‐g/d increase: hazard ratio, 0.87; 95% confidence interval, 0.81–0.94 [P<0.001]) and allium (per 5‐g/d increase: hazard ratio, 0.82; 95% confidence interval, 0.73–0.94 [P=0.003]) vegetables were inversely associated with ASVD‐related deaths. The inclusion of other vegetable types, as well as lifestyle and cardiovascular risk factors, did not alter these associations. Yellow/orange/red (P=0.463), leafy green (P=0.063), and legume (P=0.379) vegetables were not significant. Conclusions Consistent with current evidence, higher cruciferous and allium vegetable intakes were associated with a lower risk of ASVD mortality. In addition, cruciferous and allium vegetables are recognized to be a good source of several nonnutritive phytochemicals such as organosulfur compounds. Clinical Trial Registration URL: http://www.anzctr.org.au. Unique identifier: ACTRN12617000640303.

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 and fruit intake and fracture-related hospitalisations: A prospective study of older women

The importance of vegetable and fruit intakes for the prevention of fracture in older women is not well understood. Few studies have explored vegetable and fruit intakes separately, or the associations of specific types of vegetables and fruits with fracture hospitalisations. The objective of this study was to examine the associations of vegetable and fruit intakes, separately, and specific types of vegetables and fruits with fracture-related hospitalisations in a prospective cohort of women aged ≥70 years. Vegetable and fruit intakes were assessed at baseline (1998) in 1468 women using a food frequency questionnaire. The incidence of fracture-related hospitalisations over 14.5 years of follow-up was determined using the Hospital Morbidity Data Collection, linked via the Western Australian Data Linkage System. Fractures were identified in 415 (28.3%) women, of which 158 (10.8%) were hip fractures. Higher intakes of vegetables, but not fruits, were associated with lower fracture incidence. In multivariable-adjusted models for vegetable types, cruciferous and allium vegetables were inversely associated with all fractures, with a hazard ratio (HR) (95% confidence interval) of 0.72 (0.54, 0.95) and 0.66 (0.49, 0.88), respectively, for the highest vs. lowest quartiles. Increasing vegetable intake, with an emphasis on cruciferous and allium vegetables, may prevent fractures in older postmenopausal women.

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.