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The National Heart, Lung, and Blood Institute convened a virtual workshop in September 2022 to discuss “Optimal Instruments for Measurement of Diet, Physical Activity, and Sleep.” This report summarizes the proceedings, identifying current research gaps and future directions for measuring different lifestyle behaviors in adult population‐based studies. Key discussions centered on integrating report‐based methods, like questionnaires, with device‐based assessments, including wearables and physiological measures such as biomarkers and omics to enhance self‐reported metrics and better understand the underlying biologic mechanisms of chronic diseases. Emphasis was placed on the need for data harmonization, including the adoption of standard terminology, reproducible metrics, and accessible raw data, to enhance the analysis through artificial intelligence and machine learning techniques. The workshop highlighted the importance of standardizing procedures for integrated behavioral phenotypes using time‐series data. These efforts aim to refine data accuracy and comparability across studies and populations, thereby advancing our understanding of lifestyle behaviors and their impact on chronic disease outcomes over the life course.

Background Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3. Methods and Results We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography–mass spectrometry. We applied elastic net regression with 10‐fold cross‐validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1‐SD increments in the multifluid and saliva metabolomic signatures were associated with higher low‐density lipoprotein (multifluid: 12.9±5.70, P=0.02; saliva: 13.3±5.11, P=0.009). A 1‐SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P=0.02) and triglyceride (0.52±0.18, P=0.002). Conclusions Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low‐density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

Abstract Background The Mediterranean diet and other dietary patterns rich in fruits and vegetables have been linked to lower risk of frailty in older adults. However, not all plant‐based diets are necessarily healthful, and no previous study has evaluated the role of the quality of plant‐based dietary patterns in frailty risk. Our aim was to assess the association between plant‐based diet quality and risk of frailty. Methods Prospective cohort consisted with 82 234 women aged ≥60 years from the Nurses' Health Study, who were followed from 1990 through 2014. The dates of analysis were April 14 to June 23, 2021. Dietary data were collected every 4 years using a validated semi‐quantitative food frequency questionnaire. The plant‐based diet quality was assessed with two indices (range 18–90 points): (a) healthful plant‐based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils and tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, and sweets/desserts) and animal foods received reverse scores; and (b) unhealthful plant‐based diet index (uPDI) where positive scores were given to less healthy plant foods and reverse scores to healthy plant foods and animal foods. Frailty incidence was assessed every 4 years, being defined as having three or more of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses and weight loss ≥5%. Multivariable‐adjusted Cox proportional‐hazards models were used to estimate hazard ratios (HRs) and their 95% confidence interval (CI). Results We identified 12 910 incident cases of frailty over 1 176 401 person‐year follow‐up. In the multivariable analysis, the hPDI was inversely associated with the risk of frailty (hazard ratio [HR] for the highest vs. lowest quintile: 0.77, 95% confidence interval: 0.72–0.81; P trend

Abstract Background There is evidence that an overall healthy diet is associated with lower risk of frailty. However, the effect of diet composition, specifically the role of protein intake on frailty, is mostly unclear. The aim of this study was to evaluate the intake of protein, including total, plant, animal, and dairy protein, in relation to frailty incidence in a large cohort of older women. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Intake of protein was measured nine times during follow‐up from 1980 until 2010. Frailty was defined as having at least three of the following five criteria from the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight (FRAIL) scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses, and weight loss of ≥5%. The occurrence of frailty was assessed every 4 years from 1992 up to 2014. Results During follow‐up, we identified 13 279 incident cases of frailty. Women with a higher intake of plant protein had a lower risk of developing frailty after adjustment for all relevant confounders [relative risks across quintiles of consumption: 1.00, 0.94, 0.89, 0.86, and 0.86; P‐trend

Abstract Background Red meat is a nutrient‐dense source of protein fundamental for older adults; however, red meat is also high in detrimental components, including saturated fat. It is unclear whether habitual red meat consumption is associated with risk of frailty. This study aimed to examine the prospective association between the consumption of total, unprocessed, and processed red meat and the risk of frailty in older adults. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Consumption of total, unprocessed, and processed red meat was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses, and unintentional weight loss ≥5%. The occurrence of frailty was assessed every four years from 1992 to 2014. Results During 22 years of follow‐up (median follow‐up 14 years), we identified 13 279 incident cases of frailty. Women with a higher intake of red meat showed an increased risk of frailty after adjustment for lifestyle factors, medication use, and dietary factors. The relative risk (95% confidence interval) for one serving/day increment in consumption was 1.13 (1.08, 1.18) for total red meat, 1.08 (1.02, 1.15) for unprocessed red meat, and 1.26 (1.15, 1.39) for processed red meat. When each component of the frailty syndrome was individually examined, each of them was positively associated with total red meat consumption, except for the weight loss criterion. Replacing one serving/day of unprocessed red meat with other protein sources was associated with significantly lower risk of frailty; the risk reduction estimates were 22% for fish and 14% for nuts, while for replacement of processed red meat, the percentages were 33% for fish, 26% for nuts, 13% for legumes, and 16% for low‐fat dairy. Conclusions Habitual consumption of unprocessed and processed red meat was associated with a higher risk of frailty. Replacement of red meat by other protein sources might reduce the risk of frailty. These findings are in line with dietary guidelines promoting diets that emphasize plant‐based sources of protein.

Background Epidemiologic studies on the relationship between avocado intake and long‐term cardiovascular disease (CVD) risk are lacking. Methods and Results This study included 68 786 women from the NHS (Nurses’ Health Study) and 41 701 men from the HPFS (Health Professionals Follow‐up Study; 1986–2016) who were free of cancer, coronary heart disease, and stroke at baseline. Diet was assessed using validated food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios and 95% CIs. A total of 14 274 incident cases of CVD (9185 coronary heart disease events and 5290 strokes) were documented over 30 years of follow‐up. After adjusting for lifestyle and other dietary factors, compared with nonconsumers, those with analysis‐specific higher avocado intake (≥2 servings/week) had a 16% lower risk of CVD (pooled hazard ratio, 0.84; 95% CI, 0.75–0.95) and a 21% lower risk of coronary heart disease (pooled hazard ratio, 0.79; 95% CI, 0.68–0.91). No significant associations were observed for stroke. Per each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80 (95% CI, 0.71–0.91). Replacing half a serving/day of margarine, butter, egg, yogurt, cheese, or processed meats with the equivalent amount of avocado was associated with a 16% to 22% lower risk of CVD. Conclusions Higher avocado intake was associated with lower risk of CVD and coronary heart disease in 2 large prospective cohorts of US men and women. The replacement of certain fat‐containing foods with avocado could lead to lower risk of CVD.

Summary Objective Renal hyperfiltration, which has been documented in severe obesity and obesity‐associated hypertension, can occur with hypertensive disorders of pregnancy. Identification of prepregnancy risk factors for unrecognized renal hyperfiltration could inform screening and intervention strategies to protect against pregnancy complications. In young, healthy, nulliparous women, associations between associations between measures of adiposity, insulin resistance, and renal vascular resistance were thus evaluated. Methods This is a secondary analysis of a prospective observational trial characterizing associations of prepregnancy and late‐pregnancy maternal physiology. Seventy‐nine nulligravid women aged 18‐42 years without major medical conditions were assessed for percent android body fat using dual‐energy X‐ray absorption. Renal cortical vessel blood flow resistance index (CVRI) was determined using Doppler ultrasonography. Creatinine clearance was calculated from 24‐hour urine collection. Results Renal CVRI inversely correlates with body mass index (r = ‐0.23, p = 0.047), percent android fat (r = ‐0.30, p = 0.008), and supine pulse (r = ‐0.44, p < 0.001). Creatinine clearance is positively associated with BMI and HOMA‐IR. In regression modeling, supine pulse (r2 = 0.22, p < 0.001) and cardiac index (r2 = 0.05, p = 0.045) predict renal CVRI, whereas HOMA‐IR (r2 = 0.11, p = 0.008) and cardiac output (r2 = 0.06, p = 0.039) predict creatinine clearance. Measures of adiposity are not independently predictive of either measure. Conclusions In healthy young women, measures of adiposity and insulin resistance correlate positively with renal filtration. Preclinical manifestations of renal hyperfiltration may have implications for pregnancy outcomes.

Background Whether marine omega‐3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial. Methods and Results This meta‐analysis included study‐level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed‐effect meta‐analysis. A meta‐regression was conducted to estimate the dose–response relationship between marine omega‐3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE‐IT (Reduction of Cardiovascular Events with Icosapent Ethyl‐Intervention Trial), marine omega‐3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE‐IT while introducing statistically significant heterogeneity. Statistically significant linear dose–response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE‐IT. Conclusions Marine omega‐3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE‐IT. Risk reductions appeared to be linearly related to marine omega‐3 dose.

Russian wheat aphid (RWA) ( Kurdjumov) is a serious invasive pest of small-grain cereals and many grass species. An efficient strategy to defy aphid attacks is to identify sources of natural resistance and transfer resistance genes into susceptible crop cultivars. Revealing the genes helps understand plant defense mechanisms and engineer plants with durable resistance to the pest. To date, more than 15 RWA resistance genes have been identified in wheat ( L.) but none of them has been cloned. Previously, we genetically mapped the RWA resistance gene into an interval of 0.83 cM on the short arm of chromosome 7D and spanned it with five bacterial artificial chromosome (BAC) clones. Here, we used a targeted strategy combining traditional approaches toward gene cloning (genetic mapping and sequencing of BAC clones) with novel technologies, including optical mapping and long-read nanopore sequencing. The latter, with reads spanning the entire length of a BAC insert, enabled us to assemble the whole region, a task that was not achievable with short reads. Long-read optical mapping validated the DNA sequence in the interval and revealed a difference in the locus organization between resistant and susceptible genotypes. The complete and accurate sequence of the region facilitated the identification of new markers and precise annotation of the interval, revealing six high-confidence genes. Identification of as the most likely candidate opens an avenue for its validation through functional genomics approaches.

Background The previously validated Healthy Heart Score effectively predicted the 20‐year risk of cardiovascular disease (CVD). We examine whether the Healthy Heart Score may extend to an association with total and cause‐specific mortality. Methods and results The prospective cohort study investigated 58 319 women (mean age 50.2 years) in the Nurses’ Health Study (1984–2010) and 29 854 in men (mean age 52.7 years) in the Health Professionals’ Follow‐up Study (1986–2010) free of cancer and CVD at baseline. The Healthy Heart Score included baseline current smoking; high body mass index; low physical activity; no or excessive alcohol intake; low intake of fruits and vegetables, cereal fiber, or nuts; and high intake of sugar‐sweetened beverages or red/processed meats. There were 19 122 total deaths. Compared with participants in the first quintile of the Healthy Heart Score (lowest CVD risk), participants in the fifth quintile (highest CVD risk) had a pooled hazard ratio of 2.26 (95% confidence interval [CI], 1.53–3.33) for total mortality; 2.85 (95 % CI, 1.92–4.23) for CVD mortality, and 2.14 (95% CI, 1.56–2.95) for cancer mortality. Participants in the fifth versus the first quintile also had significantly greater risk of death due to coronary heart disease (3.37; 95% CI, 2.16–5.25), stroke (1.75; 95% CI, 1.02–2.99), lung cancer (6.04; 95% CI, 2.78–13.13), breast cancer (1.45; 95% CI, 1.14–1.86), and colon cancer (1.51; 95% CI, 1.18–1.93). Conclusions The Healthy Heart Score, composed of 9 self‐reported, modifiable lifestyle predictors of CVD, is a potentially useful tool for the counseling of healthy lifestyles that was strongly associated with greater risk of all‐cause, CVD, and cancer mortality.

BackgroundAlthough the timing of menarche and menopause may be associated with cardiovascular disease (CVD), the entire reproductive life span has not been considered comprehensively as risk for CVD. We investigate the associations of reproductive life span duration and ages at menarche and menopause, induced by natural means or surgical bilateral oophorectomy, with incident CVD in women. Methods and ResultsProspective cohort study of 73 814 Nurses' Health Study following participants without CVD, defined as incident coronary heart disease or stroke, from 1980 through 2012. Duration of reproductive life span was generated by subtracting age at menarche from age at menopause. A shorter reproductive life span was associated with a higher risk of incident CVD after multivariable adjustment (relative risk, 1.32 [95% confidence interval, 1.16–1.49] comparing duration

BackgroundThe relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. Methods and ResultsWe designed a case‐cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography–tandem mass spectrometry to measure, at baseline and at 1 year of follow‐up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N‐oxide, betaine, choline, phosphocholine, and α‐glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1‐SD increase in choline and α‐glycerophosphocholine metabolites were 1.24 (1.05–1.46) and 1.24 (1.03–1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21‐fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36–3.59; P

BackgroundMetabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and ResultsWe searched MEDLINE and EMBASE from inception to January 2016. Studies were eligible if they pertained to adult humans; followed an agnostic and/or comprehensive approach; used serum or plasma (not urine or other biospecimens); conducted metabolite profiling at baseline in the context of examining prospective disease; and included myocardial infarction, stroke, and/or CVD death in the CVD outcome definition. We identified 12 original articles (9 cohort and 3 nested case‐control studies); participant numbers ranged from 67 to 7256. Mass spectrometry was the predominant analytical method. The number and chemical diversity of metabolites were very heterogeneous, ranging from 31 to >10 000 features. Four studies used untargeted profiling. Different types of metabolites were associated with CVD risk: acylcarnitines, dicarboxylacylcarnitines, and several amino acids and lipid classes. Only tiny improvements in CVD prediction beyond traditional risk factors were observed using these metabolites (C index improvement ranged from 0.006 to 0.05). ConclusionsThere are a limited number of longitudinal studies assessing associations between comprehensive metabolomic profiles and CVD risk. Quantitatively synthesizing the literature is challenging because of the widely varying analytical tools and the diversity of methodological and statistical approaches. Although some results are promising, more research is needed, notably standardization of metabolomic techniques and statistical approaches. Replication and combinations of novel and holistic methodological approaches would move the field toward the realization of its promise.

Background Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate‐related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). Methods and Results Plasma levels of glutamate and glutamine were measured at baseline and 1‐year follow‐up in a case‐cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow‐up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1‐SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine‐to‐glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year‐1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. Conclusions Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine‐to‐glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. Clinical Trial Registration URL: www.controlled-trials.com. Unique identifier: ISRCTN 35739639.

BackgroundResults from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported. Methods and ResultsThree bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84–0.96; P=0.002) for stroke, 1.04 (95% CI 0.99–1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92–0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P

BackgroundEpidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and ResultsWe longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). ConclusionsIn participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial RegistrationURL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639.

Abstract Climate‐smart agriculture (CSA) is key to addressing climate change threats faced by smallholder farmers in Ghana. Nonetheless, evidence of the barriers challenging smallholder farmers in the implementation of CSA practices remains limited in Ghana. This study, therefore, investigated the barriers opposing smallholder cassava farmers in implementing CSA practices in the Afigya Kwabre South District, Ghana. The study used descriptive statistics and content analysis to analyze primary data collected through 200 household surveys and 10 key informant interviews from four selected communities (Aboabogya, Aduamoa, Aduman Old Town, and Aduman New Town) in the district. Results revealed that the smallholder cassava farmers implemented key CSA practices including mulching (89%), mixed farming (86%), crop diversification (84%), and crop rotation (81%) to build their resilience in food systems. Furthermore, the results showed that the critical enablers to the farmers’ utilization of CSA practices were access to weather and climate services (82%), a secured land tenure system (75%), and knowledge of the effects of climate change (68%). Also, the results indicated that the key barriers challenging smallholder cassava farmers in the implementation of CSA practices were inadequate technological assistance (91%), the incidence of pests and diseases (90%), and a lack of knowledge and understanding of CSA (90%). We recommend that smallholder cassava farmers adopt improved varieties of cassava that are resistant to pests and diseases, drought tolerant, high yielding, and possessing desirable quality traits. Smallholder cassava farmers can also participate in contract farming schemes that link them to agribusinesses that can offer them access to quality inputs, credit, training, and guaranteed markets for their produce.