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Research Area: Cardiovascular Health

Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults.

Jung, S., H.W. Woo, J. Shin, Y.-M. Kim, M.-H. Shin, S.-B. Koh, H.C. Kim, M.K. Kim, 2022. Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults. Eur J Nutr. doi.org/10.1007/s00394-021-02743-5.

Purpose: Maintaining optimal blood pressure (BP) levels can be an effective preventive strategy for reducing disease burden. Nut consumption may play a preventive role against hypertension, which is a lifelong condition. We aimed to prospectively examine the association between cumulative average nut consumption and the incidence of hypertension in Korean adults aged 40 years and older. Methods: A total of 10,347 participants who were free of hypertension at baseline, were included. Hypertension was defined as having a physician diagnosis and taking antihypertensive medications or having abnormal BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg). As an exposure, cumulative average nut consumption was calculated using repeated food-frequency questionnaires (mean: 2.1). We used a modified Poisson regression model with a robust error estimator to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for hypertension. Results: We identified 2047 incident cases of hypertension during 44,614 person-years of follow-up. Among both men and women, an average nut consumption of ≥ 1 serving/week (15 g/week]) was inversely associated with hypertension incidence (IRR = 0.74, 95% CI = 0.58–0.96, p for trend = 0.013 for men; IRR = 0.72, 95% CI = 0.59–0.88, p for trend = 0.002 for women) and these significant associations were consistently observed across the strata of potential confounders. Conclusion: An average consumption of at least one serving (15 g) per week of peanuts, almonds, and/or pine nuts may be inversely associated with the risk of hypertension among Korean adults aged 40 years and older, in a dose–response manner.

Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial.

Rajaram, S., M. Cofán, A. Sala-Vila, E. Haddad, M. Serra-Mir, E. Bitok, I. Roth, T.M. Freitas-Simoes, A. Kaur, C. Valls-Pedret, M. Doménech, K. Oda, D. Corella, J. Sabaté, E. Ros, 2021. Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial. Circulation. 144(13):1083–1085.

Background: Frequent consumption of nuts, an important component of plant-based diets, is associated with 15% lower total cardiovascular disease (CVD) and 23% lower CVD mortality rates. Small, short-term randomized controlled trials (RCTs) indicate that diets supplemented with nuts have a consistent cholesterol-lowering effect; however, no trials of nut-enriched diets for lipid changes focused on elderly individuals, recruited participants from diverse geographical locations, or lasted 2 years. Also, there is little information concerning effects of nuts on lipoprotein subclasses. Objective: We hypothesized that incorporating walnuts into the usual diet would improve the lipid profile irrespective of differences in geographical and dietary background. Methods: The Walnuts and Healthy Aging (WAHA) study is a two-center (Barcelona, Spain and California, USA), 2-year, parallel-group RCT testing the effects of walnut supplemented diets in healthy elders. Lipoprotein changes were a pre-specified secondary outcome. Eligible candidates were cognitively healthy elders (63-79 years-old) without major comorbidities. Participants (n=708) were allocated to either a walnut-free (control) or walnut-supplemented diet (≈15% of energy, 30-60g/day). In 2-monthly visits, compliance, tolerance, medication changes, and body weight were recorded. At each visit, 8–week allotments of raw, pieced walnuts were delivered to the corresponding group. Results: 636 participants completed the study (90% retention rate) and 628 had full data for lipoprotein analyses (mean age 69 years, 67% women, 32% treated with statins). Mean baseline LDL-C and triglycerides were 117 and 105 mg/dL, respectively. The walnut diet significantly decreased (mg/dL) total cholesterol (mean -8.5 [95% CI, -11.2, -5.4]), LDL-C (mean -4.3 [-6.6, -1.6]), and intermediate-density lipoprotein (IDL)-C (-1.3 [-1.5, -1.0]), corresponding to reductions of 4.4%, 3.6%, and 16.8%, respectively, while triglycerides and HDL-C were unaffected (Figures-B, C). Total LDL particles and small LDL particle number decreased by 4.3% and 6.1%, respectively (Figure-D). Results were not different by study site. Lipid responses to the walnut diet differed by sex: LDL-C was reduced by 7.9% in men and by 2.6% in women (P-interaction=0.007). Conclusions: The results demonstrate that incorporating daily doses of walnuts (≈15% of energy) to the habitual diet of free-living elders with an essentially normal lipid profile resulted in a mean 4.3 mg/dL LDL-C reduction, which is modest, although greater responses have been observed among individuals with hypercholesterolemia. Our data also support a beneficial effect of the walnut diet on NMR-assessed lipoprotein subfractions, with reductions of IDL-C (a sizable contributor to remnant-C) and total LDL particles. Prospective studies have reported that LDL particle number consistently outperforms LDL-C in CVD risk prediction and that remnant-C causally relates to CVD independent of LDL-C. That lipid responses were not different in two cohorts consuming diverse diets strengthens the generalization of our results. WAHA is the largest and longest nut trial to date, overcoming the limitations of prior smaller and shorter nut studies. The novel finding of sexual dimorphism in LDL-C response to walnut supplementation needs confirmation. WAHA was conducted in free-living individuals, who chose their daily foods, which may be viewed as desirable since it is closer to real life than the situation in controlled feeding studies. On the basis of associations ascertained in cohort studies, the observed shift of the lipoprotein subclass phenotype suggests a reduction of lipoprotein-related CVD risk by long-term consumption of walnuts, which provides novel mechanistic insight for their potential cardiovascular benefit beyond effects on the standard lipid panel. Our data reinforce the notion that regular walnut consumption may be a useful part of a multi-component dietary intervention or dietary pattern to lower atherogenic lipids and improve CVD risk.

Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults.

Liu, X., M. Guasch-Ferré, D.K. Tobias, Y. Li, 2021. Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults. Nutrients. 13(8), 2699. https://doi.org/10.3390/nu13082699

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses’ Health Study (1998–2018) and 26,326 men of the Health Professionals Follow-up Study (1998–2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2–4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.

Dietary recommendations for prevention of atherosclerosis

Riccardi, G., A. Giosuè, I. Calabrese, O. Vaccaro, 2021.Dietary recommendations for prevention of atherosclerosis. Cardiovasc Res. doi: 10.1093/cvr/cvab173. Online ahead of print.

This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary strategies for atherosclerosis prevention. A systematic search on PubMed was performed to identify meta-analyses of cohort studies and RCTs with CVD outcomes. The evidence is highly concordant in showing that, for the healthy adult population, low consumption of salt and foods of animal origin, and increased intake of plant-based foods-whole grains, fruits, vegetables, legumes, and nuts-are linked with reduced atherosclerosis risk. The same applies for the replacement of butter and other animal/tropical fats with olive oil and other unsaturated-fat-rich oil. Although the literature reviewed overall endorses scientific society dietary recommendations, some relevant novelties emerge. With regard to meat, new evidence differentiates processed and red meat-both associated with increased CVD risk-from poultry, showing a neutral relationship with CVD for moderate intakes. Moreover, the preferential use of low-fat dairies in the healthy population is not supported by recent data, since both full-fat and low-fat dairies, in moderate amounts and in the context of a balanced diet, are not associated with increased CVD risk; furthermore, small quantities of cheese and regular yogurt consumption are even linked with a protective effect. Among other animal protein sources, moderate fish consumption is also supported by the latest evidence, although there might be sustainability concerns. New data endorse the replacement of most high glycemic index (GI) foods with both whole grain and low GI cereal foods. As for beverages, low consumption not only of alcohol, but also of coffee and tea is associated with a reduced atherosclerosis risk while soft drinks show a direct relationship with CVD risk. This review provides evidence-based support for promoting appropriate food choices for atherosclerosis prevention in the general population.

The association between left ventricular hypertrophy and consumption of nuts, including peanuts, pine nuts, and almonds.

Park, S.K., C.-M. Oh, J.G. Kang, H.S. Seok, J.Y. Jung, 2021. The association between left ventricular hypertrophy and consumption of nuts, including peanuts, pine nuts, and almonds. Nutr Metab Cardiovasc Dis. 31(1):76-84.

Background and aims: Studies have reported that nut consumption is potentially beneficial in preventing cardiovascular disease. However, data are insufficient regarding the association between nut consumption and left ventricular hypertrophy (LVH). Methods and results: In the Kangbuk Samsung Health Study, the participants were 34,617 men and 12,257 women who completed a food-frequency questionnaire for nut consumption and received echocardiography. Nut consumption was evaluated only for peanuts, pine nuts, and almonds defining 15g as one serving/servings dose. Multivariable adjusted odds ratio (OR) and 95% confidence interval (CI) for LVH were evaluated according to the consumption frequency of one serving dose of nut. The frequency of nut consumption was categorized into five groups (<1/month, 1/month-1/week, 1-2/week, 2-4/week, and ≥4/week). The subgroup analysis was conducted by dividing the participants into the following two groups: the nonhypertensive/nondiabetic group and hypertensive or diabetic group. In women, nut consumption ≥2/week had the lower multivariable adjusted OR and 95% CI for LVH (2-4/week: 0.46 [0.26-0.81] and ≥4/week: 0.48 [0.25-0.92]) when compared with nut consumption <1/month. This association was identically observed in the subgroup analysis for women without hypertension and diabetes mellitus (DM) and women with hypertension or DM. However, men did not show the significant association. Conclusion: In women, nut consumption ≥2/week was associated with the decreased probability of LVH. Further research studies should investigate whether the beneficial effect of nut consumption on LV structure results in better cardiovascular prognosis.

Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

Tsaban, G., A. Yaskolka Meir, E. Rinott, H. Zelicha, A. Kaplan, A. Shalev, A. Katz, A. Rudich, A. Tirosh, I. Shelef, I. Youngster, S. Lebovitz,  N. Israeli, M. Shabat, D. Brikner, E. Pupkin, M. Stumvoll, J. Thiery, U. Ceglarek, J.T. Heiker, A. Körner, K. Landgraf, M. von Bergen, M. Blüher, M.J. Stampfer, I. Shai, 2020. Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. doi: 10.1136/heartjnl-2020-317802

Background: A Mediterranean diet is favourable for cardiometabolic risk. Objective To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. Methods: For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. Results: Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (−8.6 cm) than the Mediterranean (−6.8 cm; p=0.033) and HDG (−4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean −6.1 mg/dL (−3.7%), −2.3 (-0.8%), HDG −0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean −7.2 mm Hg, Mediterranean −5.2 mm Hg, HDG −3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean −0.77, Mediterranean −0.46, HDG −0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (−0.38) than in the Mediterranean (−0.21; p=0.021) and HDG (−0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (−0.52 mg/L) than in the Mediterranean (−0.24 mg/L; p=0.023) and HDG (−0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (−3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean−2.3%; p=0.073, HDG−1.4%; p<0.001). Conclusions: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.

Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease.

Tindall, A.M., C.J. McLimans, K.S. Petersen, P.M. Kris-Etherton, R. Lamendella, 2020. Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J Nutr. 2020;150(4):806-817.

Background: It is unclear whether the favorable effects of walnuts on the gut microbiota are attributable to the fatty acids, including α-linolenic acid (ALA), and/or the bioactive compounds and fiber. Objective: This study examined between-diet gut bacterial differences in individuals at increased cardiovascular risk following diets that replace SFAs with walnuts or vegetable oils. Methods: Forty-two adults at cardiovascular risk were included in a randomized, crossover, controlled-feeding trial that provided a 2-wk standard Western diet (SWD) run-in and three 6-wk isocaloric study diets: a diet containing whole walnuts (WD; 57-99 g/d walnuts; 2.7% ALA), a fatty acid-matched diet devoid of walnuts (walnut fatty acid-matched diet; WFMD; 2.6% ALA), and a diet replacing ALA with oleic acid without walnuts (oleic acid replaces ALA diet; ORAD; 0.4% ALA). Fecal samples were collected following the run-in and study diets to assess gut microbiota with 16S rRNA sequencing and Qiime2 for amplicon sequence variant picking. Results: Subjects had elevated BMI (30 ± 1 kg/m2), blood pressure (121 ± 2/77 ± 1 mmHg), and LDL cholesterol (120 ± 5 mg/dL). Following the WD, Roseburia [relative abundance (RA) = 4.2%, linear discriminant analysis (LDA) = 4], Eubacterium eligensgroup (RA = 1.4%, LDA = 4), LachnospiraceaeUCG001 (RA = 1.2%, LDA = 3.2), Lachnospiraceae UCG004 (RA = 1.0%, LDA = 3), and Leuconostocaceae (RA = 0.03%, LDA = 2.8) were most abundant relative to taxa in the SWD (P ≤ 0.05 for all). The WD was also enriched in Gordonibacter relative to the WFMD. Roseburia (3.6%, LDA = 4) and Eubacterium eligensgroup (RA = 1.5%, LDA = 3.4) were abundant following the WFMD, and Clostridialesvadin BB60group (RA = 0.3%, LDA = 2) and gutmetagenome (RA = 0.2%, LDA = 2) were most abundant following the ORAD relative to the SWD (P ≤ 0.05 for all). Lachnospiraceae were inversely correlated with blood pressure and lipid/lipoprotein measurements following the WD. Conclusions: The results indicate similar enrichment of Roseburia following the WD and WFMD, which could be explained by the fatty acid composition. Gordonibacter enrichment and the inverse association between Lachnospiraceae and cardiovascular risk factors following the WD suggest that the gut microbiota may contribute to the health benefits of walnut consumption in adults at cardiovascular risk. This trial was registered at clinicaltrials.gov as NCT02210767.

Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  

Steffen, L.M., S.Y. Yi, D. Duprez, X. Zhou, J.M. Shikany, D.R. Jacobs Jr., 2020. Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  Nutr Metab Cardiovasc Dis. S0939-4753(20)30381-1. doi: 10.1016/j.numecd.2020.09.001.  

Background and Aims: Observational studies and clinical trials have shown cardiovascular benefits of nut consumption, including walnuts. However, the relations of walnut consumption with systolic and diastolic function, risk factors for heart failure, are unknown.  We examined the associations of walnut consumption with cardiac structure and function parameters in black and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and Results: After exclusions, the study population included 3,341 participants. Dietary intake was assessed using the CARDIA Diet History questionnaire at baseline, year 7 and year 20 exams.  Cardiac structure and function were measured by echocardiography at year 25. Multivariable linear regression evaluated the associations of walnut consumption with blood pressure (BP), heart rate, and cardiac phenotypes, adjusting for age, sex, race, lifestyle habits, and clinical characteristics. We found the majority of walnut consumers compared to non-consumers were females, whites, and more highly educated, and had lower waist circumference, diastolic BP, and heart rate, and higher diet quality score. Even though cardiac structure and function measures were generally within normal ranges among participants, walnut consumers had significantly better values for diastolic function parameters A wave, E/A ratio, septal and lateral e’ than non-consumers. Further adjustment for body mass index and diabetes status did not materially change the significance between walnut consumer groups. Systolic function parameters did not differ by walnut group.  Conclusion: Compared to non-consumers, walnut consumption is associated with better diastolic dysfunction in young to middle-aged adults.

Circulating omega-3 fatty acids and incident adverse events in patients with acute myocardial infarction.

Lázaro, I., F. Rueda, G. Cediel, E. Ortega, C. García-García, A. Sala-Vila, A. Bayés-Genís, 2020. Circulating omega-3 fatty acids and incident adverse events in patients with acute myocardial infarction. J Am Coll Cardiol. 76(18):2089-2097.

Background: Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. Objectives: The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years’ follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. Methods The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. Results During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase). Conclusions: Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI.

Walnut consumption, plasma metabolomics, and risk of Type 2 diabetes and cardiovascular disease.

Guasch-Ferré, M., P. Hernández-Alonso, J.P. Drouin-Chartier, M. Ruiz-Canela, C. Razquin, E. Toledo, J. Li, C. Dennis, C. Wittenbecher, D. Corella, R. Estruch, M. Fitó, E. Ros, N. Babio, S.N. Bhupathiraju, C.B. Clish, L. Liang, M.A. Martínez-González, F.B. Hu, J. Salas-Salvadó, 2020. Walnut consumption, plasma metabolomics, and risk of Type 2 diabetes and cardiovascular disease. J Nutr. doi: 10.1093/jn/nxaa374.

Background: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. Objectives: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. Methods: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training–validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. Results: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001). Conclusions: A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.