Cardiovascular Disease Risk Reduction Research Articles

Abstract 9567: Association Between Parity and Markers of Inflammation: The Multi-Ethnic Study of Atherosclerosis

Introduction: Grand multiparity (≥5 live births) is associated with a future risk of cardiovascular disease (CVD). Inflammation also increases the risk for adverse CV outcomes and may be a mechanism linking parity to CVD. We aimed to investigate the association between parity and several markers of inflammation. Methods: We studied 3,454 female MESA participants (age 45-84 and free of CVD) who had data on parity and inflammatory markers measured at baseline. Parity (live births) was categorized as 0 (reference), 1-2, 3-4, or ≥5. Progressively adjusted linear regression models were used to evaluate the association between parity and natural log-transformed levels of fibrinogen, D-dimer, GlycA, high sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). Results: Mean age at the baseline visit was 62±10 yrs. The proportion of women with nulliparity (0), 1-2, 3-4, and ≥5 live births were 620 (18%), 1357 (39%), 1004 (29%) and 473 (14%), respectively. There was no association between parity and fibrinogen. Women with grand multiparity had 28%, 10% and 18% higher levels of hsCRP, IL-6 and D-dimer, respectively, compared to nulliparous women, after adjustment for demographic factors (Model 1). Additionally, women with 1-2 and 3-4 live births had higher hsCRP and women with 1-2 live births had higher GlycA compared to nulliparous women in the fully adjusted model (Table). Conclusion: In this diverse cohort of mid-life women free from clinical CVD, we found a history of higher parity was positively associated with specific inflammatory markers; however, these associations were largely attenuated after adjustment for lifestyle and CVD risk factors. There was no clear dose-response relationship between higher parity status and higher inflammatory levels. Future studies are needed to evaluate how inflammation may influence the link between parity and CVD, and whether lifestyle/pharmacotherapy targeting inflammation can reduce CVD risk among multiparous women.

Abstract 12011: Left Ventricular Hypertrophy Detected by Echocardiogram in Women With HIV

Introduction: Left ventricular hypertrophy (LVH) is an independent predictor of major cardiovascular events. People with HIV have an increased risk of cardiovascular disease (CVD), and a higher prevalence of LVH has been reported in this population. Women with HIV (WWH) have a higher CVD risk than their male counterparts. We sought to evaluate the current prevalence and characteristics of LVH in WWH. Methods: We performed a retrospective chart review (n=1,202) of patients seen at the University of Miami/Jackson Memorial Hospital Special Immunology clinic between 2017-2019. Of the 547 charts of WWH, 148 had available transthoracic echocardiogram. Data regarding demographic, clinical, imaging, and laboratory results was obtained. Results: The estimated prevalence of LVH in WWH was 25%. The mean age was 56.2 years. WWH with LVH were significantly older (60.7 vs. 54.9 years old, p=0.002), had higher systolic blood pressure (144 mmHg vs. 132 mmHg, p= 0.031), and left ventricle mass (169.2g vs. 128.7g, p<0.001). Those who had LVH had a higher prevalence of diastolic dysfunction (68.8% vs. 40.3%, p=0.007), diabetes (47.4% vs. 18.7%, p=0.001), hypertension (76.3% vs. 54.2%, p=0.017), heart failure (23.7% vs. 7.5% p=0.012), and CVD (47.4% vs. 24.3%, p=0.008). We found no significant difference in those with and without LVH regarding race, ethnicity, body mass index, ejection fraction, statin use, alcohol use, smoking, or HIV-related factors (CD4 count and an undetectable viral load). Conclusions: These findings suggest that WWH have a higher prevalence of LVH in the current era when compared to previous reports (15% in 2009). Furthermore, consistent with prior reports, WWH with LVH had a higher prevalence of CVD in this cohort. These findings emphasize the need to further assess risk and mechanisms for the development of LVH in WWH to help reduce CVD risk in this population.

Abstract 13528: Interventional Hepatic ApoC-III Knockdown Improves Atherosclerotic Plaque Stability and Remodeling via Lowering Remnant Lipoproteins

Introduction: Apolipoprotein C-III (apoC-III) is a key regulator in triglyceride (TG) metabolism and correlates positively with hypertriglyceridemia and incidences of CVD. Recent studies also identified apoC-III as an inducer of sterile inflammation by activating the inflammasome, another CVD risk factor. It remains unclear if therapeutic apoC-III lowering can reduce CVD risk, nor is it clear if this is dependent on lipid-lowering or anti-inflammatory properties or both. Hypothesis: We set out to test the concept that interventional apoC-III lowering reduces atherosclerosis development only when TG-lowering is achieved. Methods: We determined the impact of interventional apoC-III lowering on atherogenesis using an apoC-III antisense oligonucleotides (ASOs) in hypertriglyceridemic mouse models where the intervention results in TG-lowering ( Apoe -/- Ndst1 f/f Alb-Cre + , Ldlr -/- Ndst1 f/f Alb-Cre + ) or not ( Ldlr -/- Lrp1 f/f Alb-Cre + ). Results: ApoC-III ASO treatment did not alter atherosclerotic lesion volume in the murine models mice simultaneously fed a Western diet. However, when TG-lowering was obtained, apoC-III ASO treatment significantly attenuated advanced and unstable plaque development. In contrast, no improvement in lesion composition and hyperlipidemia was observed in apoC-III ASO-treated Ldlr -/- Lrp1 f/f Alb-Cre + mice lacking hepatic receptors responsible for apoC-III inhibition of TRL clearance. To mimic an interventional setting, we tested the impact of therapeutic apoC-III lowering in combination with a switch to a lipid-poor chow diet intervention after 12-week Western diet feeding. We observed that apoC-III ASO treatment significantly reduced atherosclerotic lesion size progression when an additive TG-lowering was achieved. No differences in lesion development were observed in similarly treated Ldlr -/- Lrp1 f/f Alb-Cre + mice wherein no additive TG-lowering was achieved by apoC-III ASO intervention. Conclusions: Our data highlight that the impact of apoC-III on atherogenesis depends on its lipid-modifying properties and suggest that interventional apoC-III lowering in hypertriglyceridemia patients can prevent plaque rupture and reduce CVD-associated mortality.

Abstract 10560: Reducing Cardiovascular Risk Among Participants in a Community Supported Agriculture Program

Introduction: Eating a diet high in vegetables translates to lower risk for cardiovascular disease. Only 10% of Americans consume the recommended servings of vegetables per day. Community supported agriculture (CSA) programs support local farmers while promoting increased consumption of vegetables. At the University of Kentucky (UK), employees receive vouchers to encourage CSA program participation while giving financial support to local farms that allow them to operate in an economically sustainable manner. Our objective was to examine the effect of participation in a CSA voucher program on CVD risk factors as a new approach to CVD risk management. Methods: Participants self-selected in the UK employee Health and Wellness CSA voucher program. Biometric measurements (blood pressure, lipid levels, and noninvasive dermal carotenoid levels via Veggie Meter) and vegetable intake via six-question BRFSS were collected pre- and post- CSA program participation. Descriptive statistics, independent t-tests, paired t-tests and cluster analysis were used to analyze the data. Results: Among 204 eligible individuals, 85 enrolled pre-program and 52 completed post program for a 61.2% retention rate. Average participant age was 42 + 10 years, predominantly Caucasian females. Systolic blood pressure was significantly reduced from pre- to post program (125.8 compared to 120.6 mmHg, p = 0.012). Carotenoid levels significantly increased from pre- to post program (286.3 ± 110 to 295.9 ± 124,) while controlling for age and sex (p = <0.001). Frequency of total vegetable, red/orange vegetables, dark green vegetables and other vegetable intake also increased from pre- to post- program while controlling for age and sex (p = 0.003, 0.004, 0.013, < 0.001 and 0.011 respectively). Conclusion: Our data identifies participation in a CSA employer incentivized program can effectively reduce blood pressure and increase vegetable intake (dermal carotenoids) and self-reported quantity and variety of vegetable consumption thereby reducing CVD risk.

Abstract 13305: The Relationship of Health Activation to Risk of Future Cardiovascular Disease Among Family Caregivers of Patients With Chronic Illness in Rural Dwellers

Background: Rural family caregivers experience high levels of stress, burden, and psychological distress related to caregiving and are at higher risk for cardiovascular disease (CVD) compared to non-caregivers. Health activation (known also as patient activation) is an indicator of engagement in self-care and is defined as an individual’s knowledge, skill, and confidence in managing health. Better health activation is associated with better health outcomes. Because rural individuals are at greater risk of CVD and have fewer supportive resources than those in urban environments, we wanted to determine the relationship of health activation with risk for future CVD in this population. Objective: The purpose of this study was to examine the association of health activation with risk for future CVD among rural family caregivers of patients with chronic illness. Methods: This was a cross-sectional study using baseline data from a randomized controlled trial of an intervention to reduce CVD risk for rural caregivers. We measured health activation using the Patient Activation Measure. The predicted10-year risk of CVD was assessed using the Framingham risk score. Covariates potentially related to cardiovascular risks among caregivers were collected including stress (Perceived Stress Scale-Cohen), anxiety (Brief Symptom Inventory), depressive symptoms (Patient Health Questionnaire-9), and caregiver burden (Zarit Burden Interview). Generalized linear regression was used to analyze data. Results: Of 217 caregivers (mean age 53 ± 13 years, 79% female), 48% were caring for a spouse, 20% were caring for a parent, and the remaining 32% were caring for a sibling, a child, or other relatives. Caregivers with higher health activation had a lower risk of developing CVD in the future based on their Framingham risk score (B = -0.081, SE= 0.039, 95% CI= -0.158 to -0.004, p=0.038), independent of the other covariates. Every 10-point increase in health activation score was associated with a nearly 1-point (0.81) decrease in Framingham risk score. Conclusions: Health activation is a good predictor of future risk for developing CVD. Development and testing of interventions to promote health activation before people develop CVD is suggested to decrease the risk of future CVD.

Abstract 10286: Age-Specific Threshold for Cardiovascular Disease Risk Stratification and Treatment Decision-Making

Introduction: Cardiovascular disease (CVD) preventative interventions are targeted at people with predicted CVD risk above pre-specified thresholds. However, younger people with high relative risks and who may benefit from intervention are often missed because their absolute risks are below the threshold. We aim to investigate the use of age- and sex-specific thresholds for CVD risk stratification for allocating statin therapy. Methods: We used primary care data from Clinical Practice Research Datalink in the UK on 1,642,498 people, aged 40-85 years and without prevalent CVD. We predicted each person’s 10-year CVD risk, using age- and sex-specific Cox models with conventional risk factors from past medical records. We compared the implications of initiating statins in people identified as being at high CVD risk from 3 strategies: a. predicted risk ≥ 10% (the recommended UK threshold); b. predicted risk ≥ 10% or above the age- and sex-specific 90 th percentile; c. predicted risk ≥ 7.5% for people aged 40-54 years, ≥ 10% for 55-69 years, and ≥ 15% for 70-85 years (an intermediate “pragmatic” approach). We calculated the C-statistic to assess the ability to discriminate high-risk people and the number needed to screen (NNS) to prevent one CVD event, assuming statin allocation reduced CVD risk by 25%. Results: Replacing the single threshold (strategy a) with age- and sex-specific thresholds (strategy b) significantly improved the discriminatory ability to identify high-risk men aged 40-45 years and high-risk women aged 40-60 years (Figure 1a). Similarly, the NNS reduced by 70% for men aged 40-45 years, and 89% for women aged 40-60 years (Figure 1b). Using pragmatic age-group thresholds (strategy c) also showed significant gains, although to a lesser degree, in discrimination and NNS for younger people. Conclusions: Our results suggest using age- and sex-specific thresholds can modestly enhance CVD risk stratification for allocation of statin therapy among younger people.

Abstract 12171: Recruitment and Enrollment of Midlife Latinas in a Multi-Component Intervention to Reduce Cardiovascular Disease Risk: Challenges and Innovations During COVID-19

Introduction: Latinos continue to be underrepresented in clinical research. The novel coronavirus (COVID-19) pandemic has presented additional challenges to conducting clinical research among Latino communities. Menopausia, Salud y Corazón is a two-group pilot intervention designed to reduce cardiovascular disease (CVD) risk in Latinas during the menopause transition. The purpose of this report is to summarize the innovative recruitment methods developed in response to COVID-19, which may enhance future clinical research with Latinas. Methods: This is a two-group, repeated measures experimental study. Eligible participants are Latinas age 40-60 years, who are perimenopausal or early postmenopausal, and free of CVD. In response to COVID-19, the recruitment and enrollment protocol was adjusted to include: remote modalities of recruitment, limited in-person visits, and adhering to COVID-19 safety guidelines (i.e., social distancing, personal protective equipment, sanitizing, temperature and symptom checklists). We recruited at drive-thru health fairs, churches, social media, and word of mouth. A bilingual research team was able to establish rapport and build relations. We developed communication strategies via mailings, infographics, phone calls, video conferencing and text messages that addressed Latino cultural values such as respeto (respect), familismo (loyalty to family), and confianza (trust). Results: After 8 months of recruitment, 79 women were screened for eligibility, with mean age 47.9 ± 5.2 years. All participants completed screening in Spanish and 16.4% (n=13) rated their overall health as “very good/excellent.” Twenty-eight (35.4%) participants screened were recruited through word of mouth and 29.1% were recruited through their parish. Of the individuals screened, 38 (48.1%) were eligible. The most common reason for ineligibility was menopause status (n=21, 26.5%) Conclusions: Despite the challenges presented by COVID-19, we found that midlife Latinas are receptive to research engagement. Researcher flexibility, multiple modalities of recruitment, a bilingual research team, and communication strategies that address cultural values are important elements for the representation of Latinas in research.

Abstract 9597: One Drop Digital App and Coaching Improves Lifestyle Risks, Glycemic Control and Psychological Well-Being in People With Hypertension and Type 2 Diabetes

Background: Mobile health interventions for reducing CVD risk have mixed effectiveness. One Drop’s (OD) digital solution integrates a mobile application, in-app coaching and connected devices (glucometer, blood pressure cuff, scale) to support management of pre-diabetes, diabetes and hypertension. Secondary analyses of the Fit-One pragmatic RCT evaluated effects of OD on lifestyle, clinical and psychological outcomes for people with CVD risks of hypertension and type 2 diabetes (T2D). Methods: Fit-One enrolled adults with diabetes (HbA1c &gt 7%) who had never used OD. Subjects were randomized to get OD only, OD with fitness tracker or a waitlist control group. Present analyses compared just OD only to control subjects with T2D and hypertension. At baseline and 3-months, subjects completed validated measures of general self-rated health (GSRH), eating behavior problems (PDQ), vigorous, moderate and walking activity (mins in past week), life satisfaction, depression (PHQ-2) and HbA1c tests. MI corrected for missingness. Intent-to-treat (ITT) and per protocol (PP) analyses used ANCOVA and logistic models controlling for baseline outcomes. Results: Participants (N=115) tended to be female, white, non-hispanic and had health insurance. Treatment (N = 58) and control (N = 57) did not differ in baseline demographics or outcomes. In ITT models, main effects for general health, moderate activity, life satisfaction and depression and significant interactions for eating behavior problems, walking and A1c indicated benefit to the OD group (p &lt .05). Vigorous activity was not significant. PP models replicated findings yet moderate activity was not significant (p = .07), likely due to lower power. Within the OD group, moderate activity increased (p = .01). Conclusions: Over 3 months, OD users realized 15% higher health ratings (from 2.2); 10% fewer eating behavior problems (from 4.1); 105% more walking, 132% more moderate activity and 55% more vigorous activity (from 77, 67, 35 mins/wk); .72% absolute reduction in A1c and 4.7 times lower risk of depression vs. control (all PP). RCT results support the effectiveness of One Drop’s digital solution in improving lifestyle risks, glycemic control and psychological well-being in people at risk for CVD.

Comparison of four healthy lifestyle scores for predicting cardiovascular events in a national cohort study

The protective effect of different healthy lifestyle scores for the risk of cardiovascular disease (CVD) was reported, although the comparisons of performance were lacking. We compared the performance measures of CVDs from different healthy lifestyle scores among Taiwanese adults. We conducted a nationwide prospective cohort study of 6042 participants (median age 43 years, 50.2% women) in Taiwan’s Hypertensive, Hyperglycemia and Hyperlipidemia Survey, of whom 2002 were free of CVD at baseline. The simple and weighted the Mediterranean diet related healthy lifestyle (MHL) scores were defined as a combination of normal body mass index, Mediterranean diet, adequate physical activity, non-smokers, regular healthy drinking, and each dichotomous lifestyle factor. The World Cancer Research Fund and American Institute for Cancer Research cancer prevention recommended lifestyle and Life's Simple 7 following the guideline definition. The incidence of CVD among the four healthy lifestyle scores, each divided into four subgroups, was estimated. During a median 14.3 years follow-up period, 520 cases developed CVD. In the multivariate-adjusted Cox proportional hazard models, adherence to the highest category compared with the lowest one was associated with a lower incidence of CVD events, based on the simple (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.2–0.94) and weighted MHL scores (HR 0.44, 95% CI 0.28–0.68). Additionally, age played a role as a significant effect modifier for the protective effect of the healthy lifestyle scores for CVD risk. Specifically, the performance measures by integrated discriminative improvement showed a significant increase after adding the simple MHL score (integrated discriminative improvement: 0.51, 95% CI 0.16–0.86, P = 0.002) and weighted MHL score (integrated discriminative improvement: 0.38, 95% CI 0.01–0.74, P = 0.021). We demonstrated that the healthy lifestyle scores with an inverse association with CVD and reduced CVD risk were more likely for young adults than for old adults. Further studies to study the mechanism of the role of lifestyle on CVD prevention are warranted.

Effects of a school-based intervention to reduce cardiovascular disease risk factors among secondary school students: A cluster-randomized, controlled trial.

BackgroundCardiovascular diseases (CVDs) are the number cause of death worldwide. In Ghana CVD has been the leading cause of death since 2001. The prevalence of CVD risk factors among adolescents in Ghana has been increasing. This study seeks to develop, implement and evaluate the effects of a behavioral modification intervention program to reduce CVD risk factors among secondary school students in Brong Ahafo, Ghana.MethodsA cluster-randomized controlled trial was conducted with schools as clusters over a period of six-months with pre and post intervention evaluations. Participants were public secondary school students (14–19 years) from four schools in Brong Ahafo, Ghana. Students in the intervention group were trained by the researchers whereas those of the control group received no intervention. The intervention included health education and physical activity modules. Follow-up data using same questionnaire were collected within two weeks after the intervention was completed. Intention-to-treat analysis was performed after replacing missing values using the multiple imputation method. The generalized linear mixed model (GLMM) was used to assess the effects of the intervention study.ResultsThe GLMM analyses showed the intervention was effective in attaining 0.77(p<0.001), 0.72(p<0.001), 0.47(p<0.001), 0.56(p<0.001), and 0.39(p = 0.045) higher total physical activity, fruits, vegetables, seafood, and water scores respectively for the intervention group over the control group. The intervention was also significant in reducing -0.15(p<0.001),-0.23(p<0.001),-0.50(p<0.001),-0.32(p<0.001),-0.90(p<0.001),-0.87(p<0.001),-0.38(p<0.001), -0.63(p<0.001), -1.63(p<0.001), 0.61(p<0.001), and -1.53(p = 0.005) carbohydrates, fats and oils, fried eggs, fried chicken, carbonated drinks, sugar, sweet snacks, salted fish, weight, BMI, and diastolic BP. The odds of quitting alcohol use in the intervention group were 1.06 times more than the control group. There was no significant effect on reducing smoking and systolic BP.ConclusionThere is an urgent need for the intervention program to be integrated into the existing curriculum structure of secondary school schools. Implementing the intervention will allow for longer and more consistent impact on the reduction of CVD risk factors among secondary school students.

"Venice marathon": participation of female Master Athletes shows a constant increase from 2003 to 2019.

The marathon is the most classic Olympic running event. In several cities worldwide it has become very popular with participation increasing during the last 20 years, particularly by Master Athletes. There are evidences that long-distance running could provide considerable health benefits for older runners, specifically risk reduction of cardiovascular diseases, cancer, diabetes, depression, and falls. Several studies have focused on the distribution of participants and their performance on famous marathons such as those of Berlin, Boston and New York. In this preliminary study we have analyzed data from several editions of the Venice marathon, a famous Italian race that attracts people from every corner of the world. The Venice marathon is listed in Abbott World Marathon Majors Wanda Age Group World Ranking and is Bronze Label certificated by IAAF, and Gold Label by FIDAL. The marathon starts outside Venice near Stra, then runs along the Brenta Riviera to Venice where the runners cross the canals over floating bridges set up for the race. For this study we analyzed data of the Venice marathon describing gender distribution in 17 editions (2003-2019), but groups of age-categories and their nationality only in 13 editions from 2007 to 2019. The analysis shows a steady increase in female participation, from 2003 to 2019.

Association between Plant-Based Dietary Patterns and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Plant-based diets, characterized by a higher consumption of plant foods and a lower consumption of animal foods, are associated with a favorable cardiovascular disease (CVD) risk, but evidence regarding the association between plant-based diets and CVD (including coronary heart disease (CHD) and stroke) incidence remain inconclusive. A literature search was conducted using the PubMed, EMBASE and Web of Science databases through December 2020 to identify prospective observational studies that examined the associations between plant-based diets and CVD incidence among adults. A systematic review and a meta-analysis using random effects models and dose–response analyses were performed. Ten studies describing nine unique cohorts were identified with a total of 698,707 participants (including 137,968 CVD, 41,162 CHD and 13,370 stroke events). Compared with the lowest adherence, the highest adherence to plant-based diets was associated with a lower risk of CVD (RR 0.84; 95% CI 0.79–0.89) and CHD (RR 0.88; 95% CI 0.81–0.94), but not of stroke (RR 0.87; 95% CI 0.73–1.03). Higher overall plant-based diet index (PDI) and healthful PDI scores were associated with a reduced CVD risk. These results support the claim that diets lower in animal foods and unhealthy plant foods, and higher in healthy plant foods are beneficial for CVD prevention. Protocol was published in PROSPERO (No. CRD42021223188).

The significant places of African American adults and their perceived influence on cardiovascular disease risk behaviors

BackgroundAA living in rural areas of the southeastern U.S. experience a disproportionate burden of cardiovascular disease (CVD) morbidity and mortality. Neighborhood environmental factors contribute to this disparity and may decrease the effectiveness of lifestyle interventions aimed at preventing CVD. Furthermore, the influence of neighborhood factors on AA CVD risk behaviors (i.e. physical activity) may be obscured by the use of researcher-defined neighborhoods and researcher-defined healthy and unhealthy places. The objective of this study was to elucidate the effects of neighborhood environments on AA CVD risk behaviors among AA adults who recently completed a lifestyle intervention. We specifically sought to identify AA adults’ self-perceived places of significance and their perceptions of how these places impact CVD risk behaviors including diet, physical activity and smoking.MethodsWe conducted semi-structured interviews with AA adults (N = 26) living in two rural North Carolina counties (Edgecombe and Nash, North Carolina, USA). Participants were recruited from a community-based behavioral CVD risk reduction intervention. All had at least one risk factor for CVD. Participants identified significant places including where they spent the most time, meaningful places, and healthy and unhealthy places on local maps. Using these maps as a reference, participants described the impact of each location on their CVD risk behaviors. Data were transcribed verbatim and coded using NVivo 12.ResultsThe average age of participants was 63 (SD = 10) and 92% were female. Places participants defined as meaningful and places where they spent the most time included churches and relatives’ homes. Healthy places included gyms and parks. Unhealthy places included fast food restaurants and relatives’ homes where unhealthy food was served. Place influenced CVD risk behaviors in multiple ways including through degree of perceived control over the environment, emotional attachment and loneliness, caretaking responsibilities, social pressures and social support.ConclusionsAs we seek to improve cardiovascular interventions for rural AA in the American South, it will be important to further assess the effect of significant places beyond place of residence. Strategies which leverage or modify behavioral influences within person-defined significant places may improve the reach and effectiveness of behavioral lifestyle interventions.

Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets.

Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.

New and emerging lipid-modifying drugs to lower LDL cholesterol

Cardiovascular disease (CVD) represents the leading cause of death worldwide. The role of low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of atherosclerosis and CVD has been well recognized. Statins are the standard of care for the management of hypercholesterolaemia, and their effectiveness in lowering LDL-C and reducing CVD risk in both primary and secondary prevention has been well established. However, several patients fail to attain optimal LDL-C goals or are intolerant to statins, especially at high doses. PCSK9 inhibitors, bempedoic acid, inclisiran, ANGPTL3 inhibitors, PPARβ/δ agonists and LXR agonists are novel or upcoming LDL-C-lowering agents that have shown promising beneficial results. This review aims to present and discuss the current clinical and scientific data pertaining to the new and emerging lipid-modifying LDL-C-lowering drugs.

Familial factors, diet, and risk of cardiovascular disease: a cohort analysis of the UK Biobank

Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD. The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD. In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006-2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies. During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption, with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89, 0.96), 0.90 (0.86, 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g., HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P-interaction<0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g., HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P<0.001]. Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention.

A Randomized, Placebo-controlled, Triple-blind Study to Determine the Effect of Farlong Ginseng Plus® NotoGinseng Extract on Cholesterol and Blood Pressure

Objective: This randomized, placebo-controlled, triple-blind study examined the efficacy of 12 weeks of Farlong NotoGinsengTM (FNG) supplementation on LDL-C and blood pressure (BP) in otherwise healthy participants (n=95) with normal to mild hypertension and hypercholesterolemia. Methods: Lipid profile, BP, and endothelial vasodilation parameters were assessed at baseline and weeks 4, 8 and 12. Safety was assessed at screening and at end of the study. The Therapeutic Lifestyle Change (TLC) diet was followed during a 4-week run-in and throughout. Results: Participants on FNG had a 4.33% reduction in LDL-C at week 8 (p=0.045) and a 1.80% improvement in HDL-C at week 12. Those on placebo had a non-significant 1.37% HDL-C reduction at both weeks 8 and 12. The FNG group showed a 0.94% reduction in systolic (SBP) and a 0.16% reduction in diastolic BP (DBP) at week 12. The placebo group had 0.5% and 1.24% increases in SBP and DBP, respectively. A total of 17.5% of participants supplemented with FNG had improvements in all three CVD risk factors (LDL-C, HDL-C, and SBP) compared to 5.0% of those on placebo (p=0.040). A greater proportion of participants with borderline high baseline LDL-C had reductions in their CVD risk factors (p=0.037) with FNG. However, participants in the placebo group with similar LDL-C characteristics did not have improvements in either their BP or lipid profile. Conclusion: FNG was well-tolerated and may have a positive influence on reducing CVD risk by improving BP and lipid profile. Left unaddressed, those with CVD risk factors may progress to a more hypertensive and hypercholesterolemic state.

Interventions to Mitigate Risk of Cardiovascular Disease After Adverse Pregnancy Outcomes

ImportanceA growing body of evidence suggests that adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy, gestational diabetes (GD), preterm birth, and intrauterine growth restriction, are associated with increased risk of cardiometabolic disease and cardiovascular disease (CVD) later in life. Adverse pregnancy outcomes may therefore represent an opportunity to intervene to prevent or delay onset of CVD. The objective of this review was to summarize the current evidence for targeted postpartum interventions and strategies to reduce CVD risk in women with a history of APOs.ObservationsA search of PubMed and Ovid for English-language randomized clinical trials, cohort studies, descriptive studies, and guidelines published from January 1, 2000, to April 30, 2021, was performed. Four broad categories of interventions were identified: transitional clinics, lifestyle interventions, pharmacotherapy, and patient and clinician education. Observational studies suggest that postpartum transitional clinics identify women who are at elevated risk for CVD and may aid in the transition to longitudinal primary care. Lifestyle interventions to increase physical activity and improve diet quality may help reduce the incidence of type 2 diabetes in women with prior GD; less is known about women with other prior APOs. Metformin hydrochloride may prevent development of type 2 diabetes in women with prior GD. Evidence is lacking in regard to specific pharmacotherapies after other APOs. Cardiovascular guidelines endorse using a history of APOs to refine CVD risk assessment and guide statin prescription for primary prevention in women with intermediate calculated 10-year CVD risk. Research suggests a low level of awareness of the link between APOs and CVD among both patients and clinicians.Conclusions and RelevanceThese findings suggest that transitional clinics, lifestyle intervention, targeted pharmacotherapy, and clinician and patient education represent promising strategies for improving postpartum maternal cardiometabolic health in women with APOs; further research is needed to develop and rigorously evaluate these interventions. Future efforts should focus on strategies to increase maternal postpartum follow-up, improve accessibility to interventions across diverse racial and cultural groups, expand awareness of sex-specific CVD risk factors, and define evidence-based precision prevention strategies for this high-risk population.

Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease.

Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. Retrospective cohort study was performed in patients (age≥18years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios=1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585mg/g; p<0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios=1.78, 95%CI: 1.42, 2.24). Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.

Primary prevention of cardiovascular disease: focus on improving behavioral risk factors

Public health strategies for the detection, prevention and treatment of cardiovascular diseases (CVDs) can be implemented at many levels as follows: from individual behavioral alterations to population-based strategies that affect different national and cultural communities. Despite the fact that the priority of primary prevention is treating hypertension and hyperlipidemia, great importance is given to improving behavioral and biological risk factors. Dietary modification, exercise and smoking cessation are specific interventions that can be targeted to reduce CVD risk at both the individual and population levels. Following a healthy lifestyle can potentially change factors such as overweight/obesity, hyperlipidemia, type 2 diabetes, and hypertension. The aim of this review was to present and summarize new data on the primary cardiovascular prevention with a focus on improving behavioral risk factors considered in the current guidelines.