Ultra-Processed Foods and Incident Cardiovascular Disease in the Framingham Offspring Study

BackgroundUltra-processed foods provide 58% of total energy in the U.S. diet, yet their association with cardiovascular disease (CVD) remains understudied.ObjectivesThe authors investigated the associations between ultra-processed foods and CVD incidence and mortality in the prospective Framingham Offspring Cohort.MethodsThe analytical sample included 3,003 adults free from CVD with valid dietary data at baseline. Data on diet, measured by food frequency questionnaire, anthropometric measures, and sociodemographic and lifestyle factors were collected quadrennially from 1991 to 2008. Data regarding CVD incidence and mortality were available until 2014 and 2017, respectively. Ultra-processed foods were defined according to the NOVA framework. The authors used Cox proportional hazards models to determine the multivariable association between ultra-processed food intake (energy-adjusted servings per day) and incident hard CVD, hard coronary heart disease (CHD), overall CVD, and CVD mortality. Multivariable models were adjusted for age, sex, education, alcohol consumption, smoking, and physical activity.ResultsDuring follow-up (1991 to 2014/2017), the authors identified 251, 163, and 648 cases of incident hard CVD, hard CHD, and overall CVD, respectively. On average, participants consumed 7.5 servings per day of ultra-processed foods at baseline. Each additional daily serving of ultra-processed foods was associated with a 7% (95% confidence interval [CI]: 1.03 to 1.12), 9% (95% CI: 1.04 to 1.15), 5% (95% CI: 1.02 to 1.08), and 9% (95% CI: 1.02 to 1.16) increase in the risk of hard CVD, hard CHD, overall CVD, and CVD mortality, respectively.ConclusionsThe current findings support that higher consumption of ultra-processed foods is associated with increased risk of CVD incidence and mortality. Although additional research in ethnically diverse populations is warranted, these findings suggest cardiovascular benefits of limiting ultra-processed foods.     

Intake of legumes and cardiovascular disease: A systematic review and dose–response meta-analysis

AimsTo summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose–response meta-analysis.Data synthesisWe have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose–response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case–control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose–response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off.ConclusionsThe intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes.     

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.     

Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study

BackgroundPreviously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.ObjectivesThe purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).MethodsSingle-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, β-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.ResultsAmong an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for β-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for γ-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.ConclusionsEvidence from our study did not support a protective effect of genetic predisposition to high dietary-derived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD.     

Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk

BackgroundA gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary atherosclerotic burden. No previous prospective study has addressed associations of long-term changes in TMAO with coronary heart disease (CHD) incidence.ObjectivesThe purpose of this study was to investigate whether 10-year changes in plasma TMAO levels were significantly associated with CHD incidence.MethodsThis prospective nested case-control study included 760 healthy women at baseline. Plasma TMAO levels were measured both at the first (1989 to 1990) and the second (2000 to 2002) blood collections; 10-year changes (Δ) in TMAO were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380).ResultsRegardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD (relative risk [RR] in the top tertile: 1.58 [95% confidence interval (CI): 1.05 to 2.38]; RR per 1-SD increment: 1.33 [95% CI: 1.06 to 1.67]). Participants with elevated TMAO levels (the top tertile) at both time points showed the highest RR of 1.79 (95% CI: 1.08 to 2.96) for CHD as compared with those with consistently low TMAO levels. Further, we found that the ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index) and was attenuated by healthy dietary patterns (p interaction = 0.008).ConclusionsLong-term increases in TMAO were associated with higher CHD risk, and repeated assessment of TMAO over 10 years improved the identification of people with a higher risk of CHD. Diet may modify the associations of ΔTMAO with CHD risk.     

Haptoglobin Phenotype Modifies the Influence of Intensive Glycemic Control on Cardiovascular Outcomes

BackgroundWhereas there exists a direct relationship between glycated hemoglobin and cardiovascular disease (CVD), clinical trials targeting glycated hemoglobin to near-normal levels using intensive therapy have failed to prevent CVD and have even increased mortality, making clinical decision making difficult. A common polymorphism at the haptoglobin (Hp) genetic locus is associated with CVD, especially coronary heart disease, in the setting of hyperglycemia.ObjectivesThis study sought to determine whether the treatment difference of intensive versus standard glucose-lowering therapy on risk of CVD events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study depended on Hp phenotype.MethodsHp phenotype was measured within 5,806 non-Hispanic white ACCORD participants using a validated assay. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different Hp phenotype groups (Hp2-2, Hp1 carriers).ResultsCompared with standard therapy, intensive therapy was associated with a lower risk of incident coronary heart disease among participants with the Hp2-2 phenotype (n = 2,133; aHR: 0.71; 95% CI: 0.55 to 0.91; p = 0.006), but not among the other 2 phenotypes (Hp1 allele carriers) (n = 3,673; aHR: 0.95; 95% CI: 0.79 to 1.13; p = 0.550). The same pattern was observed for CVD. Conversely, intensive therapy was associated with an increased risk of fatal CVD (aHR: 1.50; 95% CI: 1.00 to 2.25; p = 0.049) and total mortality (aHR: 1.40; 95% CI: 1.08 to 1.81; p = 0.011) among the Hp1 carriers, whereas this risk was not increased in the Hp2-2 phenotype (fatal CVD: aHR: 1.02; 95% CI: 0.59 to 1.77; p = 0.931; total mortality: aHR: 0.98; 95% CI: 0.68 to 1.41; p = 0.908).ConclusionsIntensive glucose-lowering therapy was effective at preventing incident coronary heart disease and CVD events in ACCORD study participants with the Hp2-2 phenotype but not in Hp1 carriers, who had increased mortality risk from intensive therapy.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).     

The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study

Background and aimsResearch suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score.Methods and resultsWe used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05–2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16–2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk.ConclusionsConsumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.     

Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia

Background and aimsBoth the Nordic and Mediterranean diets claim to have a beneficial effect on lipid metabolism and cardiovascular prevention. The objective of this study was to compare diets consumed by children with FH at the time of diagnosis in Norway and Spain and to study their relationship with the lipid profile.Methods and resultsIn this cross-sectional study, we appraised the dietary intake in children (4–18 years old) with (n = 114) and without FH (n = 145) from Norway and Spain. We compared Nordic and Mediterranean diet composition differences and determined the association between food groups and lipid profiles.ResultsThe Spanish FH group had a higher intake of total fats (mainly monounsaturated fatty acids (MUFAs)), cholesterol and fibre, but a lower intake of polyunsaturated fatty acids (PUFAs) compared to the Norwegian FH group. The Norwegian children consumed more rapeseed oil, low-fat margarine and whole grains and less olive oil, eggs, fatty fish, meat, legumes and nuts. In the Norwegian FH group, fat and MUFAs were directly correlated with total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B and inversely correlated with high-density lipoprotein (HDL-C). In Spanish children with FH, the intake of fats (mainly MUFAs) was directly associated with HDL-C and apolipoprotein A1.ConclusionsDespite a similar lipid phenotype, diets consumed by children with FH in Norway and Spain have significant differences at time of diagnosis. Nutrition advice should be more adapted to local intake patterns than on specific nutrient composition.     

Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease

BackgroundBrain injury is common in neonates with complex neonatal congenital heart disease (CHD) and affects neurodevelopmental outcomes.ObjectivesGiven advancements in perioperative care, we sought to determine if the rate of preoperative and postoperative brain injury detected by using brain magnetic resonance imaging (MRI) and associated clinical risk factors have changed over time in complex CHD.MethodsA total of 270 term newborns with complex CHD were prospectively enrolled for preoperative and postoperative brain MRIs between 2001 and 2021 with a total of 466 MRI scans. Brain injuries in the form of white matter injury (WMI) or focal stroke and clinical factors were compared across 4 epochs of 5-year intervals with logistic regression.ResultsRates of preoperative WMI and stroke did not change over time. After adjusting for timing of the postoperative MRI, site, and cardiac group, the odds of newly acquired postoperative WMI were significantly lower in Epoch 4 compared with Epoch 1 (OR: 0.29; 95% CI: 0.09-1.00; P = 0.05). The adjusted probability of postoperative WMI declined significantly by 18.7% from Epoch 1 (24%) to Epoch 4 (6%). Among clinical risk factors, lowest systolic, mean, and diastolic blood pressures in the first 24 hours after surgery were significantly higher in the most recent epoch.ConclusionsThe prevalence of postoperative WMI has declined, whereas preoperative WMI rates remain constant. More robust postoperative blood pressures may explain these findings by minimizing periods of ischemia and supporting cerebral perfusion. These results suggest potential modifiable clinical targets in the postoperative time period to minimize the burden of WMI.     

Advanced glycation end products are associated with cardiovascular risk in the Mexican population

Background and aimsChronic exposure to hyperglycemia is a significant risk factor for cardiovascular disease (CVD). Advanced glycation end products (AGES) result from multiple sugar-dependent reactions interacting with proteins and their receptors, generating endothelial dysfunction and CVD. However, there is little epidemiological data about its impact on CVD risk. We aimed to assess the association between circulating AGES and CVD risk in the Mexican population.Methods and resultsWe used longitudinal data from waves 2004–2006 and 2010–2012 of 1195 participants from the Health Workers Cohort Study. Circulating AGES were assessed by radioimmunoassay, and cardiovascular risk (CVR) was computed with the Framingham risk score. Linear and logistic fixed-effects regression models were used to assess the interest association, adjusting for confounding factors. An increase in 200 μU/ml of AGES was associated with a 0.18% increased risk of CVD (95% CI 0.05–0.31%). After adjusting for physical activity and smoking status, individuals who increased their AGES category had higher odds of middle–high CVR (low to medium AGES: OR 1.83, 95% CI 1.11–3.20; low to high AGES: OR 2.61, 95% CI 1.51–4.50). The associations remained statistically significant when we further adjusted for insulin resistance, dietary intake of AGES, and total daily calorie intake.ConclusionOur data show that circulating AGES are associated with the Framingham CVD risk score, independently of other major risk factors for CVD in the Mexican population.     

Interplay of Risk Factors and Coronary Artery Calcium for CHD Risk in Young Patients

ObjectivesThe aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients.BackgroundThe interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear.MethodsThe study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization.ResultsDuring a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC >0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10.ConclusionsIn young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients.     

Comparing Risk Scores in the Prediction of Coronary and Cardiovascular Deaths: Coronary Artery Calcium Consortium

ObjectivesThis study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE.BackgroundThe PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood.MethodsWe evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics.ResultsMean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups.ConclusionsOur findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.     

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women

Background and aimsMany dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women.Methods and resultsDairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers’ Cohort (MTC) study who were free of CVD or cancer. We categorized participants according to total dairy intake and consumption of four mutually exclusive dairy groups: high-fat, low-fat, yogurt, and dairy with added sugars. IMT and atherosclerotic plaque were measured by B-mode ultrasonography. Subclinical atherosclerosis was defined as an IMT ≥0.8 mm and/or the presence of plaque. Multivariable linear regression and logistic regression models were used to respectively assess the mean percentage difference of mean IMT and odds ratios (OR) for subclinical atherosclerosis across quantiles of dairy consumption. Mean (±SD) age was 45.4 ± 5.0 years and the median (interquartile range: IQR) total dairy consumption was 11.0 (6.6, 17.1) servings/week. After adjusting for lifestyle, clinical, and dietary factors, comparing the highest category of consumption, to the lowest, total dairy was associated with increased IMT (2.6%, 95% confidence interval (CI): 0.6, 4.3; p-trend<0.01). Moreover, yogurt consumption was associated with lower odds of subclinical atherosclerosis (OR = 0.65, 95% CI: 0.47, 0.91; p-trend = 0.01).ConclusionsWhile total dairy consumption was associated with carotid wall thickening, yogurt consumption was related to lower subclinical atherosclerosis.     

Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events

BackgroundIncreasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic individuals remain scarce.ObjectivesThis study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting.MethodsBetween 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage [IPH], lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors.ResultsDuring a median of 5.1 years’ follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 [95% confidence interval: 1.30 to 4.50], and 1.95 [95% confidence interval: 1.20 to 3.14]). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD.ConclusionsThe presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.     

Triglyceride-Rich Lipoprotein Cholesterol,Small Dense LDL Cholesterol,and Incident Cardiovascular Disease

BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women’s Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]_Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; p_trend = 0.002; PAD HR_Q4: 2.58 [95% CI: 1.18 to 5.63]; p_trend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HR_Q4: 3.71 [95% CI: 1.59 to 8.63]; p_trend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women’s Health Study; NCT00000479)     

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality

BackgroundHypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years).ObjectivesThe objective of this study was to evaluate whether HDPs were associated with premature mortality.MethodsBetween 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses’ Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders.ResultsThe authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension).ConclusionsAn occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.     

Machine Learning Adds to Clinical and CAC Assessments in Predicting 10-Year CHD and CVD Deaths

ObjectivesThe aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data.BackgroundThe CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment.MethodsThe study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT).ResultsThe AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001).ConclusionsThe comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.