Atherosclerotic Cardiovascular Risk Before and After Type 2 Diabetes Onset and the Roles of Ectopic Fat and Ethnic Variation: The 2025 Edwin Bierman Award Lecture.

Objective: With continued effort to provide optimal prevention and management of high blood pressure (BP), we compared the potential impact on prevalence of hypertension, recommended antihypertensive treatment, and achievement of target BP according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and the 2018 Korean Society of Hypertension (KSH) guidelines. Design and method: We analyzed the 2007–2017 Korea National Health and Nutrition Examination Survey data to calculate guideline-specific hypertension prevalence and treatment implications on adults aged 20 years or older by sex, age, and atherosclerotic cardiovascular disease risk. Results: The prevalence of hypertension was markedly higher 46.3% (95% confidence interval (CI) 45.6–46.9) by the ACC/AHA guideline due to the lowered BP cutoff than 25.9% (95% CI 25.4–26.5) by the KSH guideline; the increase was most pronounced in young adults. Yet, when incorporating age, atherosclerotic cardiovascular risk, comorbidity/target organ damage, there was only a marginal 1.6% (95% CI 0.9–3.0) increase in the percentage of adults who are suggested pharmacological approach by the ACC/AHA guideline, notably in the eldest subgroup. In addition, 45.6% (95% CI 44.4–46.8) of Korean adults currently undergoing antihypertensive treatment would fail to satisfy BP goal according to the 2018 KSH guideline, which would extend to 61.7% (95% CI 60.5–62.9) of participants according to the 2017 ACC/AHA guideline; the underachievement was contributed primarily by the younger subgroup. Conclusions: Despite a considerable increase in the prevalence of hypertension, the adoption of ACC/AHA guideline, regardless of sex and age, would leave modest percentage increase in adults recommended for antihypertensive medication and similar percentage of suggestions for nonpharmacological interventions, otherwise suggested also by the KSH guideline. Yet, in adherence to the ACC/AHA guideline, over half of the treated individuals would fail to achieve target BP especially in younger adults, thereby be laden with more intensive antihypertensive treatment. Despite accumulated evidence suggesting substantial cardiovascular risk reduction benefit with rigorous pharmacological approach, BP management should consider comprehensive aspects of the intended target. Future studies should assess differences in subclinical cardiovascular incidence and the benefits of long-term primary prevention of hypertension by various BP cutoffs.

Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65-79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk.

The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and applicable for general population studies. The present study was conducted to evaluate the applicability of baPWV for screening cardiovascular risk as well as for use as a marker of the severity of atherosclerotic vascular damage in a general population. baPWV was measured in a cross-sectional study involving two cohorts constituting a total of 10,828 subjects who underwent annual health screening check up examinations (6,716 males and 4,112 females; age 30 to 74 years). The Framingham risk score and Pocock's score were obtained. Multivariate analysis demonstrated that baPWV was associated with both scores, independently from conventional atherosclerotic risk factors. The receiver-operator characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk stratification by Framingham score and to discriminate patients with either stroke or coronary heart disease (n=143), but the likelihood ratios were less than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an independent variable for the risk stratification by Framingham score and for the discrimination of patients with atherosclerotic cardiovascular disease. Thus, baPWV has potential as a new marker of cardiovascular risk and may be more useful than other conventional markers; in addition, baPWV is easy to obtain and serves as an indicator of either atherosclerotic cardiovascular risk or severity of atherosclerotic vascular damage; thus it is useful to screen the general population. While the discriminating powers are not sufficiently high, a cutoff value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of either gender.

The study objectives were to measure dietary diversity (DD) of an urban US population and to determine if associations of 10 year atherosclerotic cardiovascular (ASCVD) risk with DD were independent of dietary quality. Participants were drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, wave 4 (n = 2066, 1259 African Americans (AA), 807 Whites (W). Three DD measures were derived from 2 days of 24 h recall data collected with the USDA automated-multiple-pass-method. Count was based on consumption of at least half an equivalent of food from 21 subgroups. Evenness was calculated using Berry Index (BI) and BI-adjusted by food health values. Dissimilarity was calculated by Mahalanobis Distance. Diet quality was assessed by Mean Nutrient Adequacy (MAR) and DASH scores. Associations of DD and quality with ASCVD risk, calculated using 2013 American College of Cardiology and American Heart Association guidelines, were assessed with multivariable regression. Covariates included income, education, food security, and energy/kg weight. Count and MAR were positively associated whereas dissimilarity was negatively associated with ASCVD risk. There was no evidence that evenness contributed to cardiovascular health. The findings suggest more diversity in food attributes and diets rich in micronutrients rather than increased count support cardiovascular health.

BackgroundThe prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines are not known.Methods and ResultsWe estimated prevalence of statin eligibility under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin‐therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0–16.7%) to 26.9% (95% CI 25.7–28.0%) under the 2013 ACC/AHA guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95% CI 13.0–14.7%]). Of the participants eligible for statin eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3–30.0%) and 20.6% (95% CI 19.4–21.9%) were taking statins, respectively. Statin‐eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin‐eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%, P=0.12) for Hispanic/Latinos.ConclusionsThe eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States.

Atherosclerotic cardiovascular disease is the most common cause of death in postmenopausal women. As this is a progressive disease, it is important to identify markers at an early stage during the subclinical period. Arterial calcifications are an indicator of overall atherosclerotic disease and therefore may be used as a marker for the estimation of future atherosclerotic cardiovascular events. The aims of this study are to investigate the relationship between uterine myometrial calcification (UMC) and carotid artery intima-media thickness (CIMT) and to evaluate whether UMC can be a predictive marker for the estimation of future atherosclerotic cardiovascular risk in asymptomatic postmenopausal women. In this cross-sectional study, we assessed 81 postmenopausal women without gynecological complaints for cardiovascular risk factors, UMC, and CIMT. Participants were divided into two risk groups according to their cardiovascular risk factors. The level of UMC was determined using a new scoring system, which was based on transvaginal ultrasonography. Demographic, clinical, and laboratory parameters, UMC scores, and measurements of CIMT were evaluated. A moderately positive correlation was detected between CIMT and UMC scores ( r = 0.62). There was a significant relationship between UMC scores and atherosclerotic cardiovascular risk; the risk of atherosclerosis was 15.4 times higher (OR: 15.4, 95% CI: 5.1-46.8; P = 0.001) in participants with a high UMC score (≥2). According to the multivariable logistic regression model adjusted by age and duration of menopause, the risk of cardiovascular atherosclerosis increased 27.8 fold for those with CIMT of 0.075 or greater (OR: 27.8, 95% CI: 5.3-147.1; P = 0.001) and 9.2 fold for those with a UMC score of 2 or greater (OR: 9.2, CI: 1.22-69.3; P = 0.032). The presence of UMC has been identified as an independent predictive factor for atherosclerotic risk. Accordingly, considering UMC as an atherosclerotic cardiovascular risk factor may provide an opportunity to identify cardiovascular disease in asymptomatic postmenopausal women. When UMC is detected, women should be assessed for cardiovascular risk.

Evidence increasingly suggests that ethnic differences in cardiovascular risk are partly mediated by adipose tissue biology, which refers to the regional distribution of adipose tissue and its differential metabolic activity. This paper proposes a novel evolutionary hypothesis for ethnic genetic variability in adipose tissue biology. Whereas medical interest focuses on the harmful effect of excess fat, the value of adipose tissue is greatest during chronic energy insufficiency. Following Neel's influential paper on the thrifty genotype, proposed to have been favoured by exposure to cycles of feast and famine, much effort has been devoted to searching for genetic markers of 'thrifty metabolism'. However, whether famine-induced starvation was the primary selective pressure on adipose tissue biology has been questioned, while the notion that fat primarily represents a buffer against starvation appears inconsistent with historical records of mortality during famines. This paper reviews evidence for the role played by adipose tissue in immune function and proposes that adipose tissue biology responds to selective pressures acting through infectious disease. Different diseases activate the immune system in different ways and induce different metabolic costs. It is hypothesized that exposure to different infectious disease burdens has favoured ethnic genetic variability in the anatomical location of, and metabolic profile of, adipose tissue depots.

2013 ACC/AHA cholesterol treatment guideline: Paradigm shifts in managing atherosclerotic cardiovascular disease risk

Introduction: Cardiovascular disease is a leading comorbidity in rheumatoid arthritis. Timely introduction of biologic therapies in a treat-to-target approach has optimized disease-related outcomes and attenuated accrual of comorbidities, including cardiovascular risk. Areas covered: A literature search in MEDLINE (via PubMed) was performed between January 2009 and November 2020. This manuscript explores recent developments in atherosclerotic cardiovascular risk in RA compared with non-RA individuals; it synopsizes differences in vascular function and inflammation, prevalence, burden, vulnerability, and progression of atherosclerotic plaque and their underlying cellular and molecular mechanisms. Finally, it reviews the recent literature on cardioprotective benefits of biologics and draws mechanistic links with inhibition of new plaque formation, stabilization of high-risk lesions and improvement in endothelial function, arterial stiffness, lipid metabolism, and traditional cardiac risk factors. Expert opinion: Increasing evidence points to a solid cardioprotective influence of earlier, longer, and ongoing use of biologic treatments in RA. Nevertheless, the precise mechanistic effects of plaque progression and remodeling, vascular stiffness, endothelial dysfunction, lipid metabolism, and traditional cardiac risk factors are less rigorously characterized.

The analysis aimed to quantify the number and costs of patients with type 2 diabetes and atherosclerotic cardiovascular disease or with risk factors for atherosclerotic cardiovascular disease from the Regional Health Service (RHS) perspective of the Marche region. A cost of illness (COI) model was developed to estimate the economic burden associated with diabetes and established atherosclerotic cardiovascular disease or risk factors for atherosclerotic cardiovascular disease. Data were extrapolated from the administrative database of the Marche region and specific inclusion criteria for enrolling patients were adapted from DECLARE-TIMI 58 clinical trial. RHS perspective (drugs, hospitalizations, monitoring cost) and 1 and 4-year time horizons were considered. The analysis estimated a total number of 92,205 diabetic patients in Marche region in 2014. Of these, 66,306 were patients (5.9% of the resident population) with established atherosclerotic cardiovascular disease (13,104 patients) or risk factors for atherosclerotic cardiovascular disease (53,202 patients). The annual expenditure associated with patients analysed amounted to € 98.8 million (average cost per patient € 1,480) in Marche region. Of these, 52% was associated with hospitalizations. Considering a 4-year time horizon, the overall economic burden rises to over € 301 million per year with an average cost per patient of € 4,545. Stratifying patients between patients hospitalized for heart failure and patients not hospitalized for heart failure, the average annual cost per patient was equal to € 15,896 and equal to € 3,998 respectively. An important epidemiological and economic burden associated with type 2 diabetes patients were estimated from the analysis due to the disease and the associated comorbidities. The ability to prevent comorbidity risks, especially cardiovascular ones, represents not only a clinical advantage but also a positive reduction in expenditure. Early and effective intervention represents the best strategy to avoid or slow down the evolution of complications of the disease.

BackgroundMore than 50% of patients with type 2 diabetes have hypertension in Uganda. Diabetic patients with elevated systolic blood pressure experience higher all-cause mortality and cardiovascular events compared with normotensive diabetic individuals, hence escalating resource utilization and cost of care. The aim of this study is to determine the effect of a nurse-led lifestyle choice and coaching intervention on systolic blood pressure among type 2 diabetic patients with a high atherosclerotic cardiovascular risk.MethodsThis is a cluster-randomized study comprising two arms (intervention and non-intervention—control arm) with four clusters per arm with 388 diabetic patients with a high predicted 10-year atherosclerotic cardiovascular risk. The study will be implemented in 8 health facilities in Uganda. The intervention arm will employ a nurse-led lifestyle choice and coaching intervention. Within the intervention, nurses will be trained to provide structured health education, protocol-based hypertension management, and general atherosclerotic cardiovascular risk factor management, 24-h phone calls, and 2-monthly text messaging. The control group will be constituted by the usual care. The primary outcome measure is the mean difference in systolic blood pressure between the intervention and usual care groups after 6 months. The study is designed to have an 80% statistical power to detect an 8.5-mmHg mean reduction in systolic blood pressure from baseline to 6 months. The unit of analysis for the primary outcome is the individual participants. To monitor the effect of within-cluster correlation, generalized estimating equations will be used to assess the changes over time in systolic blood pressure as a continuous variable.DiscussionThe data generated from this trial will inform change in the policy of shifting task of screening of hypertension and atherosclerotic cardiovascular disease from doctors to nurses.Trial registrationPan African Trials Registry PACTR 202001916873358. Registered on 6 October 2019

Excessive alcohol intake is a known atherosclerotic cardiovascular risk factor. However, the relation between excessive alcohol intake and atherosclerotic cardiovascular risk in subjects with normal blood pressure has not been fully elucidated. This cross-sectional study investigated the relationship between alcohol intake and arterial stiffness, as assessed using brachial-ankle pulse wave velocity, in men with normal blood pressure. Middle-aged male workers who were found to have a normal blood pressure during an annual health check-up performed in May-July 2000 (n=1,682) were enrolled in the study. The subjects' laboratory data were analyzed, and information on drinking and smoking habits was obtained by a self-administered questionnaire. The brachial-ankle pulse wave velocity was measured using volume plethysmography. The mean brachial-ankle pulse wave velocities of men with an alcohol intake of 40-59 g/day and > or =60 g/day were larger than those of non-drinkers and men with an alcohol intake of <20 g/day. A multivariate general linear model was used to identify the association between alcohol intake and brachial-ankle pulse wave velocity after controlling for other risk factors using a multivariate analysis. An alcohol intake of more than 60 g of ethanol/day was significantly associated with an elevated brachial-ankle pulse wave velocity, after controlling for conventional atherosclerotic cardiovascular risk factors. In conclusion, the present results suggest that excessive alcohol intake increases the atherosclerotic cardiovascular risk associated with arterial stiffening in men with normal blood pressure.

Fit Is It for Cardiovascular Disease Prediction, Prevention, and Treatment

Cardiovascular Risk Assessment: Practical Tips for the Internal Medicine Specialist.

Performance of the Pooled Cohort Equations in Hispanic Individuals Across the United States: Insights From the Multi‐Ethnic Study of Atherosclerosis and the Dallas Heart Study