- Title
- Investigating the role of inorganic dietary nitrate in the context of overall diet quality for cardiovascular disease prevention
- Creator
- Jackson, Jacklyn Kay
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Cardiovascular disease (CVD) remains the leading cause of death worldwide. Although the pathogenesis of CVD is complex and influenced by a variety of non-modifiable and modifiable risk factors, it has been suggested that a majority of current CVD mortality is life-style induced, and highlights the significant scope for intervention within current food and lifestyle environments. Currently, the most compelling dietary evidence for effective CVD prevention is linked to whole-diet approaches such as the Mediterranean diet (MedDiet), and other plant based/vegetable rich dietary patterns. Over the past few decades there has been significant research efforts made to understand the roles for single nutritive components of vegetables and vegetable rich diets responsible for these cardio-protective effects. One biologically plausible hypothesis has been linked to dietary nitrate consumption, which has been discussed at length in Chapter 2, including a description of the nitrate-nitrite-nitric oxide (NO) pathway as the biological pathway primarily responsible for the cardiovascular benefits of dietary nitrate. The primary dietary sources of nitrate, and factors which can influence the nitrate content of the food supply were described. The biological role for NO and other nitrogen based compounds were described within the context of the cardiovascular system, and a variety of animal and human experimental data supporting the link between dietary nitrate and a variety CVD-related outcomes were presented. In light of this developing field of research, in Chapter 3 we present our findings from a comprehensive systematic review and meta-analysis. Within this chapter, 34 experimental trials were included for qualitative synthesis. Of these, 33 focused on blood pressure, 12 on endothelial function, 10 on arterial stiffness, 4 on blood lipids and 3 on platelet aggregation, in response to an intervention of a nitrate salt (n=9), beetroot juice (n=19) or high nitrate diet (n=6). Twenty-three of the included trials were eligible for quantitative analysis. Results from the meta-analysis indicated that dietary/inorganic nitrate was significantly associated with a reduction in resting systolic blood pressure [-4.80 mmHg (95% CI: -6.59 to -3.01)] and resting diastolic blood pressure [-1.74 (95% CI: -2.72 to -0.75)], but not ambulatory measures of blood pressure. Quantitative results also found inorganic/dietary nitrate consumption to be associated with a significant rise in flow mediated dilatation [0.59% (95% CI: 0.32 to 0.86%], and reductions in arterial stiffness measured by pulse wave velocity [-0.23 m/s (95% CI: -0.35 to -0.1)] and augmentation index [-2.1% (95% CI: -4.2 to 0.003)]. Pooled nitrate intakes were also associated with reductions in platelet aggregation [-18.9% (95% CI: -26.5 to -11.3%)]. Although, meta-analysis of blood lipid trials was not possible due to the limited number of trials measuring the same lipid marker, overall the published data did not seem to support a role for nitrate in reducing blood lipid levels. Still, the evidence base indicated a beneficial effect of inorganic nitrate intakes at doses of at least 130 mg/d (equivalent to one serve of beetroot) for improving a variety of CVD risk factors, which are implicated in the development of atherosclerosis, coronary heart disease and myocardial infarction. In chapter 2 and 3, the literature supporting the link between dietary nitrate and CVD was highlight and was found to be reasonably convincing and comprehensive. However, the lack of data supporting a long-term role for habitual nitrate consumption and long-term CVD outcomes in humans in highlighted. This research gap was addressed in Chapters 4 to 8 of this thesis. In particular in Chapter 5, the association between habitual dietary nitrate intakes and risk of CHD (non-fatal myocardial infarction and fatal CHD) was prospectively examined in 62,535 women from the Nurses’ Health Study (USA). During 1,473,035 person-years of follow-up, 2267 incident cases of CHD were identified. Compared with quintile 1 (lowest nitrate intake ~63.5 mg/d), the age-adjusted relative risk (RR) of CHD in quintile 5 (highest nitrate intake ~273 mg/d) was 0.77 (95% CI: 0.68, 0.88). However, this association was no longer statistically significant once adjusted for lifestyle factors [RR: 0.91 (95% CI: 0.80, 1.04)] and was further attenuated when diet quality was added to the model [RR: 1.04 (95% CI: 0.91, 1.20)]. In Chapter 6, the relationship between habitual dietary nitrate intakes and incidence of non-fatal CVD was prospectively examined in 5,324 women from the Australian Longitudinal Study on Women’s Health (ALSWH). During 15 years of follow-up, 1951 participants reported a non-fatal CVD event (either hypertension, heart disease, thrombosis or stroke). Compared with quartile 1 for total nitrate (lowest intake <45.5mg/d), the multivariate odds ratio (OR) for non-fatal CVD in quartile 4 (highest intake >78.2mg/d) was 0.75 (95% CI: 0.63, 0.91). Compared with quartile 1 for vegetable nitrate (<34.8 mg/d), the multivariate OR for non-fatal CVD in quartile 4 (>64.4 mg/d) was 0.73 (95% CI: 0.61, 0.88). This association was not statistically significant for non-vegetable nitrate intakes, however there was a trend toward increased non-fatal CVD with increasing non-vegetable nitrate intakes from meat, processed meat, discretionary choices and alcohol [Q4: OR: 1.27 (95% CI: 1.07,1.51)]. Given that in Chapter 4, we highlight the significant positive association between total dietary nitrate consumption and diet quality scores (including the Australian Recommended Food Score (ARFS) and Mediterranean Diet Score (MDS)) within the Australian context. In Chapter 7, we also examine the association between adherence to diet quality scores including the ARFS (as a measure of adherence to the Australian Dietary Guidelines) and the MDS (as a measure of adherence of the MedDiet) and incidence of hypertension and non-fatal CVD in 5,324 women from the Australian Longitudinal Study on Women’s Health (ALSWH). During 15 years of follow-up, there were 1,342 new cases of hypertension, and 629 new cases of non-fatal CVD (either heart disease, thrombosis or stroke). Multivariate analysis indicated that women reporting better adherence to the ARFS (ARFS: ≥38/74) were at a 15% [(95% CI: 1-28%); p=0.05] lower odds of hypertension and 46% [(95% CI: 6-66%); p=0.1] lower odds of non-fatal CVD. Women reporting better adherence to the MDS (MDS: ≥8/17) were at a 27% [(95% CI: 15-47%); p=0.0006] lower odds of hypertension and 30% [(95% CI: 2-50%); p=0.03] lower odds of non-fatal CVD. In Chapter 8, we build on the research finding presented in Chapters 6 and 7, to explore the effect modification properties of diet quality scores (ARFS and MDS) on the association between total, vegetable and non-vegetable nitrate (derived from meat, discretionary choices and alcohol) and incidence of non-fatal CVD in 5,324 women from the Australian Longitudinal Study on Women’s Health (ALSWH). Findings from this analysis indicate that increased intakes of total and vegetable nitrate were significantly associated with a lower odds of non-fatal CVD, in women reporting diet quality at or above the population median for diet quality (ARFS≥32; MDS≥7). However, the association between total and vegetable nitrate consumption and non-fatal CVD were not statistically significant in women consuming diets below the population median for diet quality (ARFS<32; MDS<7). This thesis determined that clinical trials investigating the effect of inorganic nitrate interventions were found to significantly improve a variety of CVD risk factors including blood pressure, endothelial function, arterial stiffness and platelet aggregation. However, it is recommended that future trials give greater consideration to how nitrate functions within the food-matrix, and that a greater emphasis be placed on understanding the background diet of study participants, as a likely effect modifier. Despite the many limitations and challenges associated with accurately measuring population intakes of dietary nitrate, the research presented in this thesis adds to the mounting body of evidence suggesting that dietary nitrate is an important component of a healthy diet. It also provides urgently needed epidemiological evidence which suggests that habitual vegetable nitrate intakes can lower long-term risk of CVD. Findings from this thesis also emphasis that the source of dietary nitrate is important and other dietary components may modify the effect nitrate can have on human health. However, innovative research and analytic methods for accurately measuring and understanding this relationship need to be further developed.
- Subject
- dietary nitrate; diet quality; cardiovascular disease; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1406431
- Identifier
- uon:35628
- Rights
- Copyright 2019 Jacklyn Kay Jackson
- Language
- eng
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