Cardiovascular Disease Risk Reduction Research Articles

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30-50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

499 Physiological and Metabolomic Effects of a Community-Based Cardiorenal Protective Diet Intervention in African Americans with Chronic Kidney Disease and Hypertension

OBJECTIVES/GOALS: Chronic kidney disease (CKD) impacts 15% of US adults and African American (AA) persons are disproportionately affected with more than 3 times higher risk of kidney failure when compared to Caucasian persons. This study evaluated the physiological and metabolomic effects of increased fruits and vegetables (F&amp;V) on cardio-renal risk factors. METHODS/STUDY POPULATION: This pilot trial used a prospective, 2-group, randomized study design to evaluate a F&amp;V intervention (N=46), where participants received a prescribed amount of fresh, base-producing F&amp;V compared to a wait-list control (WL) condition (N=45). All participants were African American adults (≥18 years), had self-reported hypertension, and had CKD (Stage 1-3) on screening spot-urine microalbumin test. Participants were measured at baseline and 6 weeks post-intervention. Clinical data (i.e., systolic and diastolic blood pressure, lipid panel, hemoglobin A1C, BMI [body mass index], and albumin to creatinine ratio) were collected. Targeted metabolomic quantitative analysis was performed followed by LC-MS/MS and FIA-MS/MS. Linear mixed models evaluated analyte expression and clinical data. RESULTS/ANTICIPATED RESULTS: AA participants (N=91) were aged 58 ± 10.2 years, 66% female, and 54% had incomes ≤$50,000. T-tests compared change scores (baseline to 6-weeks) between groups. The F&amp;V group demonstrated a significant reduction in BMI of -4.7 ± 10.5 kg/m² compared to a 1.9 ± 8.3 kg/m² increase in the WL group, p&lt;.01. Further, the F&amp;V group demonstrated a reduction in total cholesterol of -15.4 ± 58.8 mg/dL compared to a 17.7 ± 68.8 mg/dL increase in the WL group, p&lt;.05. Non-significant reductions in hemoglobin A1c were found in the F&amp;V versus the WL group. Metabolomic analysis indicated significant variation with an increase of suggestive key biomarkers for worse CKD in the WL versus F&amp;V groups at 6-weeks. DISCUSSION/SIGNIFICANCE: Consumption of only 2 cups of F&amp;V via a community-based intervention reduced CVD risk factors in AA adults with CKD and HTN and resulted in molecular/biochemical changes which may improve long-term kidney health. Further investigation may lead to development of cost-effective dietary intervention models to improve CKD outcomes in AA persons.

Exploring the Cardio-Protective Effect of Bioactive Compounds Present in Ginger, Garlic, and Turmeric

Background: Cardiovascular diseases (CVDs) are the leading cause of mortality globally, with lifestyle and dietary habits playing crucial roles in their development and progression. Spices such as ginger, garlic, and turmeric have been traditionally recognized for their health benefits, attributed to their rich content of bioactive compounds. These spices offer potential therapeutic strategies for managing and preventing CVDs through various mechanisms, including anti-inflammatory, antioxidant, hypo-lipidemic, and anti-thrombotic properties. Objective: This review aims to synthesize current evidence on the cardioprotective effects of ginger, garlic, and turmeric, focusing on their impact on lipid profiles, endothelial function, and overall cardiovascular risk factors. Methods: A comprehensive search of databases such as PubMed, Scopus, and Web of Science was conducted to identify relevant studies published up to 2023. Criteria for inclusion encompassed clinical trials and observational studies examining the effects of ginger, garlic, and turmeric on CVD risk factors. Data on study design, population, intervention, outcomes, and conclusions were extracted and synthesized. Results: The review included studies that reported beneficial effects of ginger, garlic, and turmeric on cardiovascular health. Specifically, these spices were found to improve lipid profiles by reducing levels of total cholesterol, low-density lipoprotein (LDL), and triglycerides, while increasing high-density lipoprotein (HDL). Furthermore, they exhibited anti-inflammatory and antioxidant activities, which are vital in mitigating endothelial dysfunction and reducing cardiovascular risk. Conclusion: Ginger, garlic, and turmeric possess significant potential in reducing CVD risk through multiple mechanisms. Their inclusion in the diet may offer a natural and complementary approach to conventional CVD therapies. However, further large-scale, randomized controlled trials are necessary to confirm these findings and facilitate the integration of these spices into medical practice for CVD prevention and management.

Associations between Multiple Health Indicators and Carotid Artery Intima-Media Thickness in A Healthy and Active Elderly Population.

The purpose of this study was to examine correlations between health indicators (age, BMI, blood pressure (BP), functional strength (FS), handgrip strength, and predicted VO2 max) and carotid intima-media thickness (cIMT) in an active 50 years+ population. Study participants' mean cIMT was also compared to the cIMT mean of the general population. Health screenings were conducted on 1818 participants at the Huntsman World Senior Games from 2016 to 2019. Pearson's correlations, Spearman's correlations, and ANOVA were performed using SPSS. Weak but significant correlations were evident between cIMT and age (r = 0.283, p < 0.001), systolic BP (r = 0.253, p = 0.001), diastolic BP (r = 0.074, p = 0.016), weight (r = 0.170, p < 0.001), height (r = 0.153, p < 0.001), handgrip L (r = 0.132, p < 0.001), handgrip R (r = 0.074, p < 0.029), and BMI (r = 0.07, p = 0.029); non-significant correlations were evident with predicted VO2 max (r = -0.035, p = 0.382), and FS (r = -0.025, p = 0.597). When controlling for age, systolic BP, and sex, only handgrip L (r = 0.225, p = 0.014) was significantly correlated with cIMT. Mean cIMT for this cohort was lower across all sexes and age-matched groups (cIMT = 0.6967 mm (±0.129)). Physical activity is linked to reduced cIMT. Most health-related indicators in this study were significantly but weakly correlated with cIMT. Additional research is needed before common indicators can be used as a surrogate for cIMT and CVD risk. Results from this study can provide clinicians with additional information to reduce CVD risk through modifiable risk factors. Classic CVD risk factors such as systolic BP and BMI should be considered in patients regardless of lifestyle.

Abstract 2227: Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study

Abstract Background: Breast cancer survivors are at increased risk of cardiovascular disease (CVD) compared to women without a history of breast cancer. Although cardiotoxic cancer treatments influence these risks, lifestyles that are associated with both breast cancer and CVD also contribute. With the number of breast cancer survivors expected to increase, a growing need exists to identify modifiable risk factors that protect against the development of CVD after diagnosis. Physical activity at breast cancer diagnosis is associated with lower cancer recurrence and mortality risk. However, associations between physical activity at diagnosis and incident CVD have yet to be investigated in detail. Methods: The Pathways Study is a prospective cohort study of 4,504 women who were members of Kaiser Permanente Northern California (KPNC) when diagnosed with first primary invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their frequency, duration, and intensity of physical activities during the previous six months using the Arizona Activity Frequency Questionnaire. This information was used to dichotomize the women’s physical activity levels by the CDC’s Physical Activity Guidelines for Americans (≥ 150 minutes of moderate-to-vigorous physical activity per week vs less). CVD events were obtained from electronic health records as part of the Pathways Heart Study and were defined as post-diagnostic incidence of ischemic heart disease, heart failure, cardiomyopathy, and stroke. Deaths were documented through several sources, including the National Death Index. Women were followed until the first of disenrollment from the KPNC health plan, death, or December 31, 2021. Competing risk Cox regression models were used to estimate associations between meeting CDC physical activity guidelines and CVD. Results: In this cohort of breast cancer survivors, women who self-reported meeting physical activity guidelines at diagnosis experienced lower rates of post-diagnostic CVD events (8.6% vs 13.1%). After adjustment for socio-demographic factors, meeting physical activity guidelines remained associated with lower risk of CVD (HR: 0.78, 95% CI: 0.61, 0.98); this association appeared to be driven by reduced risk of heart failure (HR: 0.68, 95% CI: 0.50, 0.93) and cardiomyopathy (HR: 0.51, 95% CI: 0.28, 0.92). Approximately 15% of the CVD risk reduction in Pathways Study participants can be attributed to meeting physical activity guidelines (population attributable risk percent: 14.5%, 95% CI: 8%, 21%). Conclusions: Compared to women who did not meet CDC physical activity guidelines, women who reported meeting guidelines near the time of their breast cancer diagnosis had decreased risk of future CVD, including heart failure and cardiomyopathy. Future studies investigating changes in post-diagnostic physical activity patterns and CVD risk are warranted. Citation Format: Jacob K. Kresovich, Alicia R. Richards, Isaac J. Ergas, Cecile A. Laurent, Rikki Cannioto, Jamal S. Rana, Janise M. Roh, Catherine Thomsen, Salma Shariff-Marco, Eileen Rillamas-Sun, Richard K. Cheng, Song Yao, Christine B. Ambrosone, Lawrence H. Kushi, Heather Greenlee, Marilyn L. Kwan. Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2227.

Abstract P384: Longitudinal Associations of Deprived Neighborhoods With Incident Cardiovascular Disease and Cardiovascular Mortality Among UK Biobank Participants

Introduction: In 2019, the global prevalence of cardiovascular disease (CVD) reached 523 million, and CVD resulted in 18.6 million deaths. Despite well-documented associations between social determinants of health and CVD, sparse data exist on the associations between living in deprived neighborhoods and incident CVD and mortality. Hypothesis: Living in deprived neighborhoods increases the risk of CVD incidence and mortality. Methods: We analyzed the UK Biobank prospective cohort, excluding prevalent CVD cases at baseline (n=297,950, mean age=55.5 years, female=53.2%). The primary exposure was the neighborhood deprivation index (NDI), defined as an area-level proximity measure of neighborhood socioeconomic status. A higher score indicates more deprived neighborhoods (expressed in quartiles). The primary outcomes were incident CVD and CVD-related mortality, including 1) overall CVD, 2) ischemic heart disease (IHD), and 3) cerebrovascular disease (CeVD). Cox proportional-hazard regression models were used to examine associations between NDI and CVD outcomes, adjusting for covariates and reported hazard ratios (HRs) with 95% confidence intervals (CIs). Results: During a median follow-up of 14.3 years (4,261,877 person-years), 20,113 incidents and 12,619 deaths were included in the analysis. In comparison to those living in the lowest NDI quartile (least deprived), those in the highest NDI quartile (most deprived) had a 20%, 15%, and 34% greater risk of developing overall CVD, IHD, and CeVD incidence, respectively ( Table ). Moreover, they exhibited a 33%, 34%, and 35% greater risk of mortality for overall CVD, IHD, and CeVD, respectively. Conclusions: Our study demonstrates that living in highly deprived neighborhoods increased the risk for CVD, IHD, and CeVD incidence and mortality in the UK Biobank cohort. Future research should consider analyzing such linkages by sex and race and reducing CVD risk via local efforts to invest in deprived neighborhoods to alleviate the burden of CVD.

Abstract P458: Negative Mood is Associated With Sociobehavioral Factors Contributing to Cardiovascular Risk in an Immigrant Population

Introduction: Immigrants to the United States often experience structural barriers to healthy nutrition and physical activity, which increases their risk of developing obesity, cardiovascular disease (CVD), and other chronic conditions. In our prior work with immigrant communities to co-develop interventions to improve nutrition and physical activity, mood was identified as a possible mediating factor. Hypothesis: We hypothesized that self-reported negative mood would be associated with unhealthy lifestyle behaviors such as poor nutrition and less physical activity. We also evaluated the relationship between mood and sociobehavioral factors such as social support and community belongingness. Methods: The Healthy Immigrant Community (HIC) study, set in Rochester, Minnesota and embedded with the Rochester Healthy Community Partnership, is a randomized, waitlist-controlled obesity and CVD risk reduction intervention. Community-based mentoring and education for health behaviors are delivered by trained health promoters, who are members of the immigrant populations, to their social networks. Baseline self-reported and biometric measures assessed nutrition, physical activity, self-efficacy, and sociobehavioral effects on healthy lifestyle behaviors. On a single-item rating of mood over the past 7 days, responses of poor or fair were considered “negative”, while good, very good, or excellent were considered “positive”. Results: The HIC study enrolled 475 adult participants; 268 Hispanic/Latino and 181 Somali participants completed baseline measures and were included in this analysis. Of the 449 participants, 107 (24%) reported “negative” mood. This group was more likely to be Hispanic/Latino (74%), female (68%), uninsured in the past 12 months (46%), or younger age (mean = 41 years; range = 18-79). Participants who endorsed negative mood at baseline had lower healthy nutrition scores ( p =0.02), lower physical activity scores ( p =0.03), and less confidence in eating healthily ( p =0.001). Those reporting negative mood also reported less support from family and friends to eat healthy ( p =&lt;0.001) and be physically active ( p =0.01), accessed community resources for healthy eating ( p =0.001) and physical activity ( p =&lt;0.01) less often, and reported less sense of belonging to their community ( p =0.01) than those with positive mood. Conclusion: Negative mood was significantly associated with eating a less healthy diet and being sedentary, lower confidence in maintaining a healthy diet, less perceived social support for healthy behaviors, and less sense of belonging to the community among Hispanic/Latino and Somali immigrants. Behavioral interventions designed to support a healthy lifestyle may benefit from incorporating culturally-aligned mood management and sociobehavioral strategies to reduce CVD risk and promote health equity in immigrant populations.

Abstract MP12: Educational Attainment and the Effect of Intensive Blood Pressure Reduction: A Post-Hoc Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Introduction: Hypertension is a major risk factor for cardiovascular disease (CVD). The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that systolic blood pressure (SBP) &lt;120 mm Hg reduced CVD risk and all-cause mortality among those with elevated SBP and high CVD risk. Educational attainment (EA) is associated with CV health, but whether EA modifies the effect of intensive SBP reduction remains unclear. Hypothesis: We predicted that SPRINT participants with lower EA would have greater CVD risk reduction with intensive SBP lowering than those with higher EA. Methods: We included 9,361 individuals recruited as part of the SPRINT study and categorized them by EA (&lt;college, some college through college graduate, and &gt;college degree). We examined the effect of intensive SBP lowering across EA strata in relation to the composite endpoint defined by SPRINT (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or CV death) in multivariable proportional hazards models. Results: The cohort was age 67.9±9.4 years, 35.6% female, and 57.8% White race. Those with high EA were more likely to be older, male, and White race. Higher EA was associated in a dose-response manner with a larger reduction in the risk of developing the composite endpoint after intensive SBP lowering [highest to lowest EA: adjusted HR 0.48 (95% CI: 0.34, 0.70); 0.81 (0.63, 1.03); 0.90 (0.70, 1.15); P , interaction=0.01] ( Table ). The interaction between intensive SBP lowering and EA was limited to non-Black individuals; among Black participants, the association of SBP lowering with the endpoint did not differ significantly by EA. Conclusion: In the SPRINT cohort, higher EA was associated with a larger improvement in CV outcomes after intensive SBP reduction, with differences by race or ethnicity. This post-hoc SPRINT analysis suggests that the benefit of intensive SBP lowering varies by EA, and highlights a need for tailored approaches to optimize hypertension management for individuals with different social backgrounds.

Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with &gt;95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p&lt;0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p&lt;.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.

Abstract P231: Are Resiliency and Religiosity/Spirituality Associated With Better Sleep Outcomes in Midlife Latinas?

Background: The disproportionate cardiovascular disease (CVD) burden among Latinas is not completely explained. An important health behavior in CVD prevention is sleep. In the United States (U.S.), Latinas experience unique sociocultural stressors that may impact sleep, particularly in midlife. Yet, little is known about protective factors such as resiliency and religiosity/spirituality among midlife Latinas. Aims: To assess the relation of resiliency and religiosity/spirituality with sleep disturbances in midlife Latinas. Methods: We conducted a cross-sectional analysis using baseline data from 49 participants in a pilot study to reduce CVD risk in midlife Latinas. Participants were Latinas aged 40-60 years who were perimenopausal or early postmenopausal, free of CVD, with no menopause hormone therapy use in the prior three months. Women were recruited from community settings. The frequency of sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) over the past two weeks was assessed, and a sum score was created (0-16). The 6-item Brief Resilience Scale was used to assess the perceived ability to “bounce back” or recover from hardship. Religiosity/spirituality was determined by self-report (how important is religion/spirituality to you). Multivariable linear regression models were performed at p&lt;0.15, adjusting for sociodemographic. Results: Participants were on average aged 47.1±4.5 years, 47% had less than a high school education, and 98% were born outside of the continental U.S. Sixty-nine percent of women experienced trouble falling asleep. The mean sleep score was 6.9±4.6. In adjusted models, we found an inverse relationship between resiliency and sleep (ß[SE]= -0.33[0.13],p=0.01). Religiosity/spirituality was not related to sleep disturbances (ß[SE]= 1.15[1.60],p=0.48). Conclusions: In this analysis of midlife Latinas, higher resiliency was associated with poorer sleep. Findings suggest that the ability to “bounce back” after hardship and religiosity/spirituality may not buffer the negative impact of stress on sleep. Further research is necessary with objective sleep measures to identify protective factors for sleep disturbances that may subsequently improve CVD risk in midlife Latinas.

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels. A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles: a randomized, controlled crossover trial

BackgroundExtracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and are considered emerging markers of CVDs. n-3 PUFAs are abundant in oily fish and fish oil and are reported to reduce CVD risk, but there has been little research to date examining the effects of n-3 PUFAs on the generation and function of EVs. ObjectivesWe aimed to investigate the effects of fish oil supplementation on the number, generation, and function of EVs in subjects with moderate risk of CVDs. MethodsA total of 40 participants with moderate risk of CVDs were supplemented with capsules containing either fish oil (1.9 g/d n-3 PUFAs) or control oil (high-oleic safflower oil) for 12 wk in a randomized, double-blind, placebo-controlled crossover intervention study. The effects of fish oil supplementation on conventional CVD and thrombogenic risk markers were measured, along with the number and fatty acid composition of circulating and platelet-derived EVs (PDEVs). PDEV proteome profiles were evaluated, and their impact on coagulation was assessed using assays including fibrin clot formation, thrombin generation, fibrinolysis, and ex vivo thrombus formation. Resultsn-3 PUFAs decreased the numbers of circulating EVs by 27%, doubled their n-3 PUFA content, and reduced their capacity to support thrombin generation by >20% in subjects at moderate risk of CVDs. EVs derived from n-3 PUFA-enriched platelets in vitro also resulted in lower thrombin generation, but did not alter thrombus formation in a whole blood ex vivo assay. ConclusionsDietary n-3 PUFAs alter the number, composition, and function of EVs, reducing their coagulatory activity. This study provides clear evidence that EVs support thrombin generation and that this EV-dependent thrombin generation is reduced by n-3 PUFAs, which has implications for prevention and treatment of thrombosis. Clinical Trial RegistryThis trial was registered at clinicaltrials.gov as NCT03203512.

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease.

Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.

Association of Achievement of the American Heart Association's Life's Essential 8 Goals With Incident Cardiovascular Diseases in the SHFS.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in American Indian people. In 2022, the American Heart Association developed the Life's Essential 8 goals to promote cardiovascular health (CVH) for Americans, composed of diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood pressure, and blood glucose. We examined whether achievement of Life's Essential 8 goals was associated with incident CVD among SHFS (Strong Heart Family Study) participants. A total of 2139 SHFS participants without CVD at baseline were included in analyses. We created a composite CVH score based on achievement of Life's Essential 8 goals, excluding sleep. Scores of 0 to 49 represented low CVH, 50 to 69 represented moderate CVH, and 70 to 100 represented high CVH. Incident CVD was defined as incident myocardial infarction, coronary heart disease, congestive heart failure, or stroke. Cox proportional hazard models were used to examine the relationship of CVH and incident CVD. The incidence rate of CVD at the 20-year follow-up was 7.43 per 1000 person-years. Compared with participants with low CVH, participants with moderate and high CVH had a lower risk of incident CVD; the hazard ratios and 95% CIs for incident CVD for moderate and high CVH were 0.52 (95% CI, 0.40-0.68) and 0.25 (95% CI, 0.14-0.44), respectively, after adjustment for age, sex, education, and study site. Better CVH was associated with lower CVD risk which highlights the need for comprehensive public health interventions targeting CVH promotion to reduce CVD risk in American Indian communities.

Beyond Statins: Novel Lipid-Lowering Agents for Reducing Risk of Atherosclerotic Cardiovascular Disease

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort

IntroductionThe impact of residential green spaces on cardiovascular health in older adults remains uncertain. MethodsCohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF‐15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). ResultsAfter adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of −5.56 % (95 %CI: −9.77; −1.35), −5.05 % (-9.58; −0.53), −4.24 % (-8.19, −0.19), and −4.16 % (-7.59; −0.74), respectively; and mean differences in hs-TnT among diabetic participants of −8.03 % (95 %CI: −13.30; −2.77), −9.52 % (-16.08; −2.96), −8.05 % (-13.94, −2.16) and −5.56 % (-10.75; −0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. ConclusionIncreased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Cardiovascular disease risk scores in patients with optimal vs suboptimal weight loss after bariatric surgery: Translating improvements into clinical practice

IntroductionThe aim of this study was to evaluate cardiovascular disease (CVD) risk modification in patients with optimal weight loss (OWL) versus suboptimal weight loss SWL following MBS. MethodsThis was a retrospective analysis. The 10-year risk CVD was estimated before and after one year of surgery using the “Framingham Score”. Results191 patients were included in our study. Mean baseline Framingham score was 7.2 ​± ​6.9%. According to the score, 54% of patients were classified as low risk (n ​= ​104), 23% as moderate (n ​= ​43), 20% moderately high (n ​= ​39) and 3% as high risk (n ​= ​5). One year after surgery, 91% of the patients showed reduction of their Framingham score. Mean CVD risk score decreased significantly to 4.1 ​± ​3.7% when compared to baseline (p-value is ​< ​0.001); 80% of patients classified as low risk (n ​= ​153), 13% as moderate (n ​= ​25), 7% moderately high (n ​= ​13) and 0% as high risk (n ​= ​0). ConclusionWeight loss after bariatric surgery reduces CVD risk scores and the magnitude of effect correlates with the degree of weight loss.

Impact of High-Intensity Interval Training (HIIT) on Cardiovascular Health in Middle-Aged Chinese Populations

This paper examines the impact of High-Intensity Interval Training (HIIT) on cardiovascular health among the middle-aged Chinese population, amidst the country’s growing burden of cardiovascular diseases (CVDs). Given the escalating prevalence of CVDs influenced by lifestyle changes, aging, and dietary shifts, there’s a pressing need for efficient and accessible interventions. HIIT, with its brief, intense exercise bursts followed by rest periods, emerges as a potent modality to enhance cardiovascular fitness, manage weight, improve metabolic health, and address psychological stress factors, thereby reducing CVD risk factors. This analysis is grounded in research findings, health statistics, and pilot program outcomes, underscoring HIIT’s viability as a public health strategy. The paper delves into the physiological benefits of HIIT, including improvements in VO2 max, blood pressure regulation, lipid profile enhancement, and insulin sensitivity. It also considers the implementation challenges and strategies for HIIT in China, highlighting the role of technology, healthcare provider collaboration, and tailored community initiatives in promoting widespread HIIT adoption. The conclusions drawn emphasize HIIT’s significant potential in mitigating cardiovascular risk among middle-aged Chinese, advocating for its integration into national health promotion efforts.

Achieving Better Understanding of Obstructive Sleep Apnea Treatment Effects on Cardiovascular Disease Outcomes through Machine Learning Approaches: A Narrative Review.

Obstructive sleep apnea (OSA) affects almost a billion people worldwide and is associated with a myriad of adverse health outcomes. Among the most prevalent and morbid are cardiovascular diseases (CVDs). Nonetheless, randomized controlled trials (RCTs) of OSA treatment have failed to show improvements in CVD outcomes. A major limitation in our field is the lack of precision in defining OSA and specifically subgroups with the potential to benefit from therapy. Further, this has called into question the validity of using the time-honored apnea-hypopnea index as the ultimate defining criteria for OSA. Recent applications of advanced statistical methods and machine learning have brought to light a variety of OSA endotypes and phenotypes. These methods also provide an opportunity to understand the interaction between OSA and comorbid diseases for better CVD risk stratification. Lastly, machine learning and specifically heterogeneous treatment effects modeling can help uncover subgroups with differential outcomes after treatment initiation. In an era of data sharing and big data, these techniques will be at the forefront of OSA research. Advanced data science methods, such as machine-learning analyses and artificial intelligence, will improve our ability to determine the unique influence of OSA on CVD outcomes and ultimately allow us to better determine precision medicine approaches in OSA patients for CVD risk reduction. In this narrative review, we will highlight how team science via machine learning and artificial intelligence applied to existing clinical data, polysomnography, proteomics, and imaging can do just that.