Dietary patterns are key modifiable determinants in cardiovascular disease (CVD) prevention, accounting for over half of CVD-related deaths and disabilities. This study aimed to examine whether changes in diet quality and six predefined diet scores were associated with incident cardiovascular (CV) events over four years among secondary care cardiology patients. We conducted a secondary prospective analysis of participants aged ≥45 years from the Brazilian Cardioprotective Nutritional Program Trial, including 1,704, 1,629 and 1,286 individuals for the 12-, 24- and 36-month change analyses, respectively. The assessed diet scores included the Dietary Inflammatory Index (DII), Dietary Total Antioxidant Capacity (dTAC), overall, healthful and unhealthful Plant-Based Diet Index (PDI, hPDI, uPDI), and the modified Alternative Healthy Eating Index (mAHEI). The primary outcome was the incidence of new CV events in each follow-up period, adjudicated by the Clinical Endpoints Committee. Associations were estimated using Cox proportional hazards models, combining intervention and control groups. A total of 162 incident CVD cases occurred over a median follow-up of 3.25 years. After 36 months, improvements in mAHEI scores were inversely associated with CV event incidence in both crude (HR: 0.96; 95% CI: 0.92–0.99) and adjusted models (HR: 0.94; 95% CI: 0.89–1.00). No significant associations were found for changes in DII, dTAC, PDI, hPDI or uPDI across any time point. These findings suggest that, in individuals receiving secondary CV care, sustained improvements in diet quality, particularly those reflected by the mAHEI, may require longer periods to translate into measurable benefits for cardiovascular health.

Inflammation and oxidative stress contribute to the progression of chronic diseases, and the volume of research in this area is rapidly expanding. Various dietary indices have been developed to determine the overall inflammatory or oxidative stress potential of a diet; however, few have been validated in cardiometabolic disease populations. This review aimed to explore the association between dietary indices and biomarkers of inflammation and oxidative stress in adults with cardiometabolic conditions. Four databases were systematically searched for literature in any language (Embase, CINAHL, CENTRAL and MEDLINE) with 12,286 deduplicated records identified. Seventeen studies of adults with metabolic syndrome, cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease or chronic kidney disease were included. Fourteen studies were observational studies, one study was a clinical trial, and one was a randomised controlled trial. Four dietary indices were reported on with most studies (n 11) reporting on the dietary inflammatory index. The most reported biomarker was C-reactive protein. The findings were narratively synthesised. Results were inconclusive due to the heterogeneity of dietary indices and their use, disease states and biomarkers reported. Only one study reporting on the dietary inflammatory index assessed all 45 parameters. Observational studies, particularly retrospective designs (n 7), are subject to recall and selection biases, potentially presenting overestimated results. Further research is required to determine the relationship between dietary indices and biomarkers of inflammation and oxidative stress in cardiometabolic disease populations. Future research should be prospective, utilise rigorous research methods, assess the full range of index parameters, and examine biomarkers the tool was developed for.

n-3 PUFA delivered by fish oil supplements alter the number and functions of circulating extracellular vesicles (EV), but consumption of oily fish does not reproduce this effect. In order to assess the effects of fish oil supplements and oily fish, at a level achievable in the diet, on EV numbers, composition and procoagulant activity in healthy human volunteers, forty-two healthy subjects were assigned to one of three treatment groups: (i) fish oil supplements plus white fish meals, (ii) control supplements plus oily fish meals or (iii) control supplements plus white fish meals for 12 weeks in a randomised, double-blind, placebo-controlled, parallel trial; circulating EV were enumerated and their procoagulant activity assessed using thrombin generation and fibrinolysis assays. Our results showed that fish oil supplements decreased circulating EV numbers and reduced EV-stimulated thrombin generation, but the consumption of oily fish at half the dose of EPA had no effect on either EV number or thrombogenic capacity. Consumption of both oily fish and fish oil supplements increased the EPA and DHA contents of EV, and the proportion of EPA in circulating EV was strongly associated with EV-stimulated thrombin generation. This study revealed that the additional 1 g/d EPA delivered in the fish oil supplements is required to decrease the numbers and thrombogenic capacity of EV, since oily fish at a level achievable in the diet had no effect. Increasing EPA intake beyond current guidelines for oily fish consumption may therefore be required for cardiovascular benefits relating to EV.

Saccharin is a widely used sugar substitute, but little is known about the long-term health effects of saccharin intake. Our study aimed to examine the association between saccharin intake and mortality in diabetic and pre-diabetic population and overweight population from NHANES 1988–1994. Cox proportional hazard models were used to evaluate the association between saccharin intake and CVD, cancer and all-cause mortality. After multivariable adjustment, increased absolute saccharin intake was associated with the risk of all-cause mortality (hazard ratio (HR): 1·41, 95 % CI: 1·05, 1·90), CVD mortality (HR: 1·93, 95 % CI: 1·15, 3·25) and cancer mortality (HR: 2·26, 95 % CI: 1·10, 4·45) in diabetic and pre-diabetic population. Among overweight population, higher absolute saccharin intake was associated with the risk of cancer mortality (HR: 7·369, 95 % CI: 2·122, 25·592). Replacing absolute saccharin intake with total sugar significantly reduced all-cause mortality by 12·5 % and CVD mortality by 49·7 % in an equivalent substitution analysis in the diabetic and pre-diabetic population. Aspartame substitution reduced all-cause mortality by 29·2 % and cancer mortality by 30·2 %. Notably, the relative daily intake of saccharin also had similar effects as the absolute intake on all-cause, cardiovascular and cancer mortality in all analyses. This was despite the fact that the relative daily intake in our study was below the Food and Drug Administration limit of 15 mg/kg. In conclusion, our study showed a considerable risk of increased saccharin intake on the all-cause, CVD mortality and cancer mortality.

Epidemiological and clinical trial evidence indicates that n-6 polyunsaturated fatty acid (PUFA) intake is cardioprotective. Nevertheless, claims that n-6 PUFA intake promotes inflammation and oxidative stress prevail. This narrative review aims to provide health professionals with an up-to-date evidence overview to provide the requisite background to address patient/client concerns about oils containing predominantly unsaturated fatty acids (UFA), including MUFA and PUFA. Edible plant oils, commonly termed vegetable oils, are derived from vegetables, nuts, seeds, fruits and cereal grains. Substantial variation exists in the fatty acid composition of these oils; however, all are high in UFA, while being relatively low in saturated fatty acids (SFA), except for tropical oils. Epidemiological evidence indicates that higher PUFA intake is associated with lower risk of incident CVD and type 2 diabetes mellitus (T2DM). Additionally, replacement of SFA with PUFA is associated with reduced risk of CVD and T2DM. Clinical trials show higher intake of UFA from plant sources improves major CVD risk factors, including reducing levels of atherogenic lipids and lipoproteins. Importantly, clinical trials show that increased n-6 PUFA (linoleic acid) intake does not increase markers of inflammation or oxidative stress. Evidence-based guidelines from authoritative health and scientific organisations recommend intake of non-tropical vegetable oils, which contain MUFA and n-6 PUFA, as part of healthful dietary patterns. Specifically, vegetable oils rich in UFA should be consumed instead of rich sources of SFA, including butter, tallow, lard, palm and coconut oils.

Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial.

Diet is a contributing factor to CVD risk, but how diet quality changes over the long term and contributes to CVD risk is less well studied. Diet data were analysed from parents and offspring from the Princeton Lipid Research Study (24-h recall in the 1970s; Block FFQ in 1998). Diet quality was assessed using an 8-point Dietary Approaches to Stop Hypertension nutrient-based scoring index, including a new method for scoring in children, as well as examining twelve key macro/micronutrients. Outcomes included blood glucose, blood pressure, serum lipids and BMI. The analysis included 221 parents (39 % male, mean age 38·9 ± 6·5 at baseline and 66·6 ± 6·6 at follow-up) and 606 offspring (45 % male, 11·9 ± 3·2 at baseline and 38·5 ± 3·6 at follow-up). Parents’ Dietary Approaches to Stop Hypertension score increased slightly from baseline to follow-up (1·4 ± 1·0 and 2·1 ± 1·3, respectively, P < 0·001), while offspring remained consistent (1·6 ± 0·9 and 1·6 ± 1·1, respectively, P = 0·58). Overall, the Dietary Approaches to Stop Hypertension score, adjusted for age, race, sex and BMI, was not significantly associated with any examined outcomes. Of the macro/micronutrients at follow-up, saturated and total fat were associated with increased diabetes and dyslipidaemia in parents, while the inverse was seen with niacin. Among offspring, niacin was associated with lower rates of hypertension and dyslipidaemia. In conclusion, no relationship was detected between Dietary Approaches to Stop Hypertension adherence and disease outcomes. However, both saturated fat and niacin were associated with components of CVD risk, highlighting the need for improved diet quality overall.

The contribution of dietary saturated fatty acids (SFA) to cardiovascular disease (CVD) and mortality remains debated after decades of research. Few previous studies had repeated dietary assessments and power to assess mortality. Evidence for individual SFA is limited. In this large population-based cohort study, we investigated associations between intake of total and individual SFA and risk of total and CVD mortality. Adult residents (mean 41·1 years at baseline) in three Norwegian counties were invited to repeated health screenings between 1974 and 1988 (> 80 % attendance). We calculated cumulative average intakes of macronutrients from semi-quantitative FFQ. Median (interquartile range) intake of SFA was 14·6 % (12·8–16·6 %) of total energy (E%). Hazard ratios (HR) and 95 % CI were estimated using multivariable Cox regression models to assess total, CVD, ischaemic heart disease (IHD) and acute myocardial infarction (AMI) mortality. Among 78 725 participants, 28 555 deaths occurred during a median follow-up of 33·5 years, with 9318 deaths due to CVD. Higher intake of SFA (replacing carbohydrates) was positively associated with all mortality endpoints, including total (HR per 5 E% increment, 1·18; 95 % CI 1·13, 1·23) and CVD mortality (1·16; 95 % CI 1·07, 1·25). Theoretical isoenergetic substitution of SFA with carbohydrates or MUFA was associated with lower risk. Of individual SFA, myristic (14:0) and palmitic acid (16:0) were positively associated with mortality. In summary, dietary SFA intake was strongly associated with higher total and CVD mortality in this long-term cohort study. This supports policies implemented to reduce SFA consumption in favour of carbohydrates and unsaturated fats.

Machine learning methods have been used in identifying omics markers for a variety of phenotypes. We aimed to examine whether a supervised machine learning algorithm can improve identification of alcohol-associated transcriptomic markers. In this study, we analysed array-based, whole-blood derived expression data for 17 873 gene transcripts in 5508 Framingham Heart Study participants. By using the Boruta algorithm, a supervised random forest (RF)-based feature selection method, we selected twenty-five alcohol-associated transcripts. In a testing set (30 % of entire study participants), AUC (area under the receiver operating characteristics curve) of these twenty-five transcripts were 0·73, 0·69 and 0·66 for non-drinkers v. moderate drinkers, non-drinkers v. heavy drinkers and moderate drinkers v. heavy drinkers, respectively. The AUC of the selected transcripts by the Boruta method were comparable to those identified using conventional linear regression models, for example, AUC of 1958 transcripts identified by conventional linear regression models (false discovery rate < 0·2) were 0·74, 0·66 and 0·65, respectively. With Bonferroni correction for the twenty-five Boruta method-selected transcripts and three CVD risk factors (i.e. at P < 6·7e-4), we observed thirteen transcripts were associated with obesity, three transcripts with type 2 diabetes and one transcript with hypertension. For example, we observed that alcohol consumption was inversely associated with the expression of DOCK4, IL4R, and SORT1, and DOCK4 and SORT1 were positively associated with obesity, and IL4R was inversely associated with hypertension. In conclusion, using a supervised machine learning method, the RF-based Boruta algorithm, we identified novel alcohol-associated gene transcripts.

CVD is the leading cause of death worldwide, and is commonly associated with modifiable risk factors. Most studies to date examining link between food intake and risk of CVD, have focused on modulation of plasma cholesterol concentrations (total cholesterol (TC), LDL-C). However, recent studies suggest LDL particle size is a more sensitive risk marker for CVD with smaller, dense LDL particles reported as more atherogenic than larger, more buoyant LDL. Although dietary guidelines recommend SFA intake of < 10 % of total energy, this does not consider food source, with recent evidence suggesting differing, sometimes beneficial, lipid responses following consumption of SFA from dairy compared to other food sources. This may be from differences in the physical food matrices, the nutrient content of the foods, and/or how these components interact with each other, described as a ‘dairy matrix effect’. Dietary fat not only raises LDL-C, but also HDL cholesterol (HDL-C), associated with reduced CVD risk. HDL particles are complex emulsions of lipids, proteins and microRNAs that exhibit atheroprotective properties. In addition, HDL particles exhibit a very heterogeneous proteomic composition, dependent on a person’s disease state – with a more pro-inflammatory proteome evident in patients with established CVD. This review will discuss the evidence to date on the importance of the food matrix in modulating response to dietary SFA and impact on CVD risk factors. A focus on potential biomarker properties of lipoprotein particles beyond cholesterol and current use of such biomarkers in human nutrition research will be considered.

The aim of this review is to provide an overview of the history in support of the role of dietary saturated fatty acids (SFA) in the development of cardiovascular disease (CVD), and the controversy and consensus for the evidence in support of guidelines to remove and replace SFA with unsaturated fatty acids. The review will also examine the existence, origins, and implications for CVD risk of variability in serum LDL-cholesterol in response to these guidelines. While the quality of supporting evidence for the efficacy of restricting SFA on CVD risk has attracted controversy, this has helped to increase understanding of the inter-relationships between SFA, LDL-cholesterol and CVD, and reinforce confidence in this dietary recommendation. Nevertheless, there is significant inter-individual variation in serum LDL-C in response to this dietary change. The origins of this variation are multi-factorial and involve both dietary and metabolic traits. If serum biomarkers of more complex metabolic traits underlying LDL-responsiveness can be identified, this would have major implications for the targeting of these dietary guidelines to LDL-responders, to maximise the benefit to their cardiovascular health.

Sichuan cuisine was previously fitted into the Chinese Heart-Healthy Diet (CHH) trial to verify the antihypertensive effect. Whether the modified Sichuan diet lessens cardiovascular disease (CVD) is not fully explored. We aimed to estimate the effects of the Sichuan version of CHH diet (CHH diet-SC) on the 10-year risk of CVD and vascular age. A single-blinded randomised controlled feeding trial was conducted. General CVD prediction model was used in manners of intention-to-treat and per-protocol set. After a 7-d run-in period, fifty-three participants with pre- and grade I hypertension from local communities were randomised and provided with either CHH diet-SC (n 27) or a control diet (n 26) for 4 weeks. Mean absolute and relative estimated CVD risks were reduced by 4·5 % and 27·9 % in the CHH diet-SC group, and the between-group relative risk reduction was 19·5 % (P < 0·001) using linear mixed-effects models. The sensitivity analysis with datasets and models showed consistent results, and pre-specified factors were not associated with the intervention effects. The vascular age of CHH-SC group was theoretically 4·4 years younger than that of the control group after intervention. Compared with a typical diet, adopting the CHH diet-SC over 1 month significantly reduced 10-year CVD risks and vascular ages among local adults with mild hypertension.

The review aims to explore the potential benefit and risk of high-protein diets (HPD) regarding the comorbidity of sarcopoenia and CVD in the setting of cardiac rehabilitation (CR). CR is standard care for individuals who have experienced a cardiac event, but the current practice of predominantly aerobic exercise, a lower-fat diet and weight loss poorly addresses the issue of sarcopoenia. HPD, especially when combined with resistance exercise (RE), may be valuable adjuncts to current CR practice and benefit both muscle and cardiovascular health. Meta-analyses and randomised controlled trials of HPD and CVD risk show beneficial but variable effects regarding weight loss, the lipid profile, insulin resistance and lean body mass in those living with or high risk of CVD. Meta-analyses of prospective cohort studies on hard CVD endpoints favour lower- and plant-protein diets over higher animal protein, but the evidence is inconsistent. HPD augment the strength and muscle gaining benefits of RE in older populations, but there are no published data in those living with CVD providing promising opportunities for CR research. HPD raise concern regarding renal and bone health, the microbiome, branched chain amino acids and environmental sustainability and findings suggest that plant-based HPD may confer ecological and overall health advantages compared to animal-based HPD. However, incorporating RE with HPD might alleviate certain health risks. In conclusion, a largely plant-based HPD is deemed favourable for CR when combined with RE, but further research regarding efficacy and safety in CR populations is needed.

The current study aimed to investigate the cardiovascular effects of epicatechin, a flavonoid found in green tea and cocoa, in attenuating complications associated with metabolic syndrome in diet-induced obese rats. Male Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Epicatechin treatment (5 mg/kg/d) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, cardiac electrical function, aortic and mesenteric vessel reactivity were examined after the treatment. Twenty weeks of HFHC feeding in WKY rats resulted in the development of metabolic syndrome indicated by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and increased blood pressure. Epicatechin treatment was found to enhance the oxidative stress status in HFHC groups through an increase in serum nitric oxide levels and a decrease in 8-isoprostane concentrations. Furthermore, WKY-HFHC rats displayed a decrease in IL-6 levels. The lipid profiles in HFHC groups showed improvement, with a decrease in LDL-cholesterol and TAG and an increase in HDL-cholesterol levels observed in WKY-HFHC rats. However, epicatechin was not effective in preventing weight gain, glucose intolerance or hypertension in HFHC fed rats. Overall, the results of this study suggest that epicatechin has the potential to improve the underlying mechanisms associated with metabolic syndrome in obese rats.

Over the years, numerous observational studies have substantiated that various dietary choices have opposing effects on CVD. However, the causal effect has not yet been established. Thus, we conducted a Mendelian randomisation (MR) analysis to reveal the causal impact of dietary habits on CVD. Genetic variants strongly associated with 20 dietary habits were selected from publicly available genome-wide association studies conducted on the UK Biobank cohort (n 449 210). Summary-level data on CVD were obtained from different consortia (n 159 836–977 323). The inverse-variance weighted method (IVW) was the primary outcome, while MR-Egger, weighted median and MR Pleiotropy RESidual Sum and Outlier were used to assess heterogeneity and pleiotropy. We found compelling evidence of a protective causal effect of genetic predisposition towards cheese consumption on myocardial infarction (IVW OR = 0·67; 95 % CI = 0·544, 0·826; P = 1·784 × 10−4) and heart failure (IVW OR = 0·646; 95 % CI = 0·513, 0·814; P = 2·135 × 10−4). Poultry intake was found to be a detrimental factor for hypertension (IVW OR = 4·306; 95 % CI = 2·158, 8·589; P = 3·416 × 10−5), while dried fruit intake was protective against hypertension (IVW OR = 0·473; 95 % CI = 0·348, 0·642; P = 1·683 × 10−6). Importantly, no evidence of pleiotropy was detected. MR estimates provide robust evidence for a causal relationship between genetic predisposition to 20 dietary habits and CVD risk, suggesting that well-planned diets may help prevent and reduce the risk of CVD.