Associations between life's essential 8 and metabolic health among us adults: insights of NHANES from 2005 to 2018.

BACKGROUND: Metabolic unhealth (MUH) is closely associated with cardiovascular disease (CVD). Life's Essential 8 (LE8), a recently updated cardiovascular health (CVH) assessment, has some overlapping indicators with MUH but is more comprehensive and complicated than MUH. Given the close relationship between them, it is important to compare these two measurements. METHODS: This population-based cross-sectional survey included 20- to 80-year-old individuals from 7 National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Based on the parameters provided by the American Heart Association, the LE8 score (which ranges from 0 to 100) was used to classify CVH into three categories: low (0-49), moderate (50-79), and high (80-100). The MUH status was evaluated by blood glucose, blood pressure, and blood lipids. The associations were assessed by multivariable regression analysis, subgroup analysis, restricted cubic spline models, and sensitivity analysis. RESULTS: A total of 22,582 participants were enrolled (median of age was 45 years old), among them, 11,127 were female (weighted percentage, 49%) and 16,595 were classified as MUH (weighted percentage, 73.5%). The weighted median LE8 scores of metabolic health (MH) and MUH individuals are 73.75 and 59.38, respectively. Higher LE8 scores were linked to lower risks of MUH (odds ratio [OR] for every 10 scores increase, 0.53; 95% CI 0.51-0.55), and a nonlinear dose-response relationship was seen after the adjustment of potential confounders. This negative correlation between LE8 scores, and MUH was strengthened among elderly population. CONCLUSIONS: Higher LE8 and its subscales scores were inversely and nonlinearly linked with the lower presence of MUH. MUH is consistent with LE8 scores, which can be considered as an alternative indicator when it is difficult to collect the information of health behaviors.

Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.

BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications. METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set. CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.

Left ventricular hypertrophy phenotype to predict incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIM: Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF. METHODS AND RESULTS: This study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77-6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30-4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001). CONCLUSIONS: The risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model.

Association between 5-year change in cardiovascular risk and the incidence of atherosclerotic cardiovascular diseases: a multi-cohort study.

BACKGROUND: The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence. METHODS: We analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40-75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD. RESULTS: Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59-0.77) or high to non-high (HR, 0.57; 95% CI 0.41-0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29-0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26-2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84-2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69-3.42) also showed an increased risk of incident ASCVD. CONCLUSIONS: Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.

Weigh change across adulthood is related to the presence of NAFLD: results from NHANES III.

BACKGROUND: Obesity is a widely recognized driving factor of Non-alcoholic fatty liver disease (NAFLD), it remains unclear whether historical weight status was associated with the presence of NAFLD. The study aimed to explore the relationship between weight change across adulthood and the presence of NAFLD. METHODS: Data from the National Health and Nutrition Examination Survey III included 6586 participants. Weight change was assessed according to body mass index (BMI) at baseline, at 25 years old, and 10 years before baseline. Obesity was defined as BMI ≥ 30 kg/m2. NAFLD was assessed by hepatic ultrasonography. RESULTS: The prevalence of NAFLD was highest among stable obese participants (48.1%), and the lowest among stable non-obese participants (18.9%). Among non-obese participants, those who get obese in early adulthood had a higher risk for the presence of NAFLD than those who were never obese (odds ratio [OR], 1.82; 95% confidence interval [CI] 1.17-2.92). Among obese participants, those who become obese in middle-late adulthood had a lower risk of NAFLD (OR, 0.79; 95% CI 0.65-0.96) than those with stable obesity. A weight gain of more than 12 kg and 4 kg since early and middle-late adulthood respectively were associated with increased risks of NAFLD. CONCLUSION: Among current nonobese individuals, those with a history of obesity in their early adulthood had a higher risk of NAFLD than those never obese. Among the currently obese population, those who became obese after mid-adulthood have a significantly lower risk of NAFLD compared with those who were stable obese.

Association of Life's Essential 8 with all-cause and cardiovascular mortality among US adults: A prospective cohort study from the NHANES 2005-2014.

BACKGROUND AND AIMS: This study aims to investigate the association of Life's Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with long-term outcomes among US adults. METHODS AND RESULTS: This population-based prospective cohort study analyzed data of 23,110 participants aged 20 years or older from the National Health and Nutrition Examination Survey from 2005 to 2014 and their linked mortality data through December 2019. LE8 score (range 0-100) was measured according to AHA definitions and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. The weighted mean age of the study population was 47.0 years (95% confidence interval [CI], 46.4-47.5 years), and 11,840 were female (weighted percentage, 51.5%; 95% CI, 50.9-52.1%). During a median follow-up period of 113 months (up to 180 months), 2942 all-cause deaths occurred, including 738 CVD deaths. The LE8 score was significantly and inversely related to mortality from all causes (adjusted hazard ratio [HR] for per 10-score increase in LE8 score, 0.86; 95% CI, 0.82-0.90) and cardiovascular disease (adjusted HR for per 10-score increase in LE8 score, 0.81; 95% CI, 0.75-0.87). Compared with participants having low CVH, those having high CVH had a reduction of 40% (adjusted HR, 0.60; 95% CI, 0.48-0.75) in the risk for all-cause mortality and 54% (adjusted HR, 0.46; 95% CI, 0.31-0.68) in the risk for cardiovascular mortality. CONCLUSIONS: Higher LE8 score was independently associated with lower risks of all-cause and cardiovascular mortality among US adults.

Novel metabolic phenotypes for extrahepatic complication of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Phenotypic heterogeneity among patients with NAFLD is poorly understood. We aim to identify clinically important phenotypes within NAFLD patients and assess the long-term outcomes among different phenotypes. METHODS: We analyzed the clinical data of 2311 participants from the Third National Health and Nutrition Examination Survey (NHANES III) and their linked mortality data through December 2019. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other liver diseases and excess alcohol use. A 2-stage cluster analysis was applied to identify clinical phenotypes. We used Cox proportional hazard models to explore all-cause and cause-specific mortality between clusters. RESULTS: We identified 3 NAFLD phenotypes. Cluster 1 was characterized by young female patients with better metabolic profiles and lower prevalence of comorbidities; Cluster 2 by obese females with significant insulin resistance, diabetes, inflammation, and advanced fibrosis and Cluster 3 by male patients with hypertension, atherogenic dyslipidemia, and liver and kidney damage. In a median follow-up of 26 years, 989 (42.8%) all-cause mortality occurred. Cluster 1 patients presented the best prognosis, whereas Cluster 2 and 3 had higher risks of all-cause (Cluster 2-adjusted HR: 1.48, 95% CI: 1.16-1.90; Cluster 3-adjusted HR: 1.29, 95% CI: 1.01-1.64) and cardiovascular (Cluster 2-adjusted HR: 2.01, 95% CI: 1.18-3.44; Cluster 3-adjusted HR: 1.75, 95% CI: 1.03-2.97) mortality. CONCLUSIONS: Three phenotypically distinct and clinically meaningful NAFLD subgroups have been identified with different characteristics of metabolic profiles. This study reveals the substantial disease heterogeneity that exists among NAFLD patients and underscores the need for granular assessments to define phenotypes and improve clinical practice.

Characteristics, Treatment, and Mortality of Patients Hospitalized for First ST-Segment Elevation Myocardial Infarction without Standard Modifiable Risk Factors in China.

Background: Little is known of the characteristics, treatment, and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) but without standard modifiable cardiovascular risk factors (SMuRFs, including smoking, hypercholesterolemia, diabetes, and hypertension) in developing countries like China. Moreover, contributors to the excess mortality of such SMuRF-less patients remain unclear. Methods: This study was based on a nationally representative sample of patients presenting with STEMI and admitted to 162 hospitals in 31 provinces across mainland China between 2001 and 2015. We compared clinical characteristics, treatments, and mortality during hospitalization between patients with and without SMuRFs. We also investigated the possible causes of differences in mortality and quantified the contributors to excess mortality. Results: Among 16,541 patients (aged 65 ± 13 years; 30.0% women), 19.9% were SMuRF-less. These patients were older (69 vs. 65 years), experienced more cardiogenic shock and lower blood pressure at admission, and were less likely to be admitted to the cardiac ward compared to patients with SMuRFs. Moreover, SMuRF-less patients received treatment less often, including primary percutaneous coronary intervention (17.3% vs. 28.8%, p < 0.001), dual antiplatelet therapy (59.4% vs. 77.0%, p < 0.001), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (49.9% vs. 68.1%, p < 0.001), and statins (69.9% vs. 85.1%, p < 0.001). They had higher in-hospital mortality (18.5% vs. 10.5%, p < 0.001), with 56.1% of deaths occurring within 24 hours of admission. Although the difference in mortality decreased after adjusting for patient characteristics, it remained significant and concerning (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.25-1.59). Mediation analysis found that, in patients without SMuRFs, underutilization of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins contributed to an excess mortality risk of 22.4% and 32.5%, respectively. Conclusions: Attention and action are urgently needed for STEMI patients without SMuRFs, given their high incidence and excess in-hospital mortality. The use of timely and adequate evidence-based treatments should be strengthened.

Associations between life's essential 8 and non-alcoholic fatty liver disease among US adults.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with Cardiovascular disease (CVD). We aim to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of NAFLD among US adults. METHODS: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2017-2018 and included adults 20 years or older. LE8 score (range 0-100) was measured according to American Heart Association definitions and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. NAFLD was determined by transient elastography measured hepatic steatosis in the absence of other liver diseases and excess alcohol use. Multivariable logistic and restricted cubic spline models were used to assess the associations. RESULTS: Among 3588 participants included (weighted mean age, 48.0 years; 95% confidence interval [CI] 46.4-49.7 years), 1839 were female (weighted percentage, 51.6%; 95% CI 49.0-54.2%) and 1483 were determined to have NAFLD (weighted percentage, 36.5%; 95% CI 33.3-39.7%). The weighted mean LE8 score of the study population was 67.9 (95% CI 66.6-69.2). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of NAFLD (odds ratio [OR] for per 10 score increase, 0.67; 95% CI 0.59-0.76) and a nonlinear dose-response relationship was observed. Similar patterns were also identified in the association of health behavior and health factor scores with NAFLD. The inversed association of LE8 score and NAFLD was significantly stronger among younger, Asian, and participants with higher education and income level. CONCLUSIONS: LE8 and its subscales scores were negatively associated with the presence of NAFLD in non-linear fashions. Promoting adherence to optimal CVH levels may be beneficial to reduce the burden of NAFLD as well as CVD.

Association of nighttime physical activity with all-cause and cardiovascular mortality: Results from the NHANES.

Background: Nighttime physical activity (PA) has significant effects on human health. Whether excessive nighttime PA is associated with adverse long-term prognosis remains unknown. Methods: Three thousand six hundred ninety adults from the US National Health and Nutrition Examination Survey (NHANES) 2003-2006 with accelerometer monitor recording PA data were included. Nighttime PA was quantified by the nighttime to all-day PA intensity ratio (NAPAIR). Participants with the NAPAIR above the population median (0.17) were defined as the nighttime active population (NAP), otherwise as the daytime active population. All-cause and cardiovascular disease mortality status was acquired from the US National Death Index from their interview and physical examination date through December 31, 2015. Results: Among 3690 adults (weighted mean age 48.1 years), 1781 (weighted proportion 48.8%) were females. One thousand eight hundred six (48.9%) were determined as the NAP. During the follow-up period of up to 13.1 years (median, 10.7 years), 639 deaths occurred (heart diseases, 114). Multivariable Cox proportional hazards model showed that the NAP was associated with higher risks of all-cause (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.22-1.75) and cardiovascular disease (HR, 1.58; 95% CI, 1.03-2.41) mortality compared with the daytime active population, and each 0.1 increase in the NAPAIR was associated with 15% increased all-cause mortality risks. Conclusion: In this nationally representative prospective cohort study of a sample of United States adults, excessive nighttime PA was associated with a higher risk of death from all causes and cardiovascular disease.

Atherosclerotic Cardiovascular Disease Risk and Lipid-Lowering Therapy Requirement in China.

Background: Lipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit. Methods: We conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015-2020), from which we included 2,904,914 participants aged 35-75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification. Results: After standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals -8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)-would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively. Conclusions: Moderate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10-25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.