Associations between insulin resistance indices and subclinical atherosclerosis: A contemporary review.

Even in the absence of hyperglycemia or hyperlipidemia, it has been demonstrated that insulin resistance is an independent risk factor for atherosclerosis. Finding markers of insulin resistance that are associated with markers of atherosclerosis could help identify patients early in their disease course and allow for earlier initiation of preventative treatments. We reviewed available evidence regarding associations between known markers of insulin resistance and known markers of atherosclerosis. Serum triglycerides (TG), triglyceride-glucose index (TyG), and homeostasis model assessment (HOMA) were the insulin resistance markers reviewed. The coronary artery calcium score (CAC), carotid intimal medium thickness (cIMT), and pulse wave velocity (PWV) were reviewed as markers of atherosclerosis. TyG showed the most consistent association with CAC across broad demographic groups, though HOMA showed potential in obese individuals and those without diabetes. The data regarding cIMT and the reviewed insulin resistance markers did not yield any consistent associations, though very elevated TyG did appear to be associated with cIMT among normal weight individuals. Serum triglycerides showed a strong and consistent association with PWV across numerous studies and populations, though TyG index also demonstrated a strong association with PWV in a large systematic review. Of the insulin resistance markers reviewed, the TyG index appears to be most consistently associated with markers of atherosclerosis. TyG can be easily calculated with routine labwork and has the potential to inform decisions regarding early initiation of therapies in patients who would otherwise not be treated. Targeting insulin sensitivity prior to the development of T2DM has the potential to reduce development and progression of atherosclerosis, and patients without T2DM but who have elevated TyG index should be the topic of further research.

Effect of vigorous-intensity physical activity on incident cognitive impairment in high-risk hypertension.

INTRODUCTION: We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. METHODS: Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. RESULTS: Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9 vs 19.7), probable dementia (6.3 vs 9.0), and MCI/probable dementia (18.5 vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. DISCUSSION: This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. HIGHLIGHTS: Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.

Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

AIMS: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. METHODS AND RESULTS: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). CONCLUSION: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Higher levels of small dense particles of LDL cholesterol, better known as the 'bad cholesterol', are associated with a greater risk for the presence of coronary artery calcium, a strong marker for heart disease, even when accounting for estimated total (small dense + large body particles) LDL cholesterol.This risk is stronger in older individuals.Peak risk seems to occur between 49 and 71 mg/dL and does not increase further at higher levels.

Association between weight variability, weight change and clinical outcomes in hypertension.

Objective: The effect of body weight variability (BWV) and body weight change (BWC) in high-risk individuals with hypertension, but without diabetes mellitus (DM) remains unclear. We examined the effect of BWV and BWC on the primary outcome [the composite of myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure (HF), or cardiovascular (CV) death] and all-cause mortality in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: In this post-hoc analysis, we used multivariate Cox regression models to examine the risk associated with BWV and BWC for the primary outcome in SPRINT. BWV was defined as the intra-individual average successive variability (ASV). BWC was defined as baseline weight minus final weight. Results: A total of 8714 SPRINT participants (mean age 67.8 ± 9.4 years, 35.1 % women, 58.9 % Whites) with available data on body weight were included. The median follow-up was about 3.9 years (IQR, 3.3-4.4). In multivariable-adjusted Cox models, each 1 unit standard deviation (SD) of BWV was significantly associated with a higher risk for the primary outcome, all-cause mortality, HF, MI, and stroke [HR(95 % CI)]: 1.13 (1.07-1.19; p < 0.0001), 1.22 (1.14-1.30; p < 0.0001), 1.16 (1.07-1.26; p < 0.001), 1.10 (1.00-1.20; p = 0.047), and 1.15 (1.05-1.27; p = 0.005), respectively. Similarly, each 1 unit SD of BWC was significantly associated with a higher risk of the primary outcome, all-cause mortality, MI, and HF: 1.11(1.02-1.21; p = 0.017), 1.44 (1.26-1.65; p < 0.0001), 1.16 (1.01-1.32; p = 0.041) and 1.19 (1.02-1.40; p = 0.031) respectively. However, there was no significant association with CV death (for both BWV and BWC) or stroke (BWC). Conclusion: In high-risk hypertension, BWV and BWC were both associated with higher risk of the primary outcome and all-cause mortality. These results further stress the clinical importance of sustained weight loss and minimizing fluctuations in weight in hypertension.

Association Between Alcohol Consumption and Ectopic Fat in the Multi-Ethnic Study of Atherosclerosis.

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log-transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1-27.7], hepatic 3.4 [95% CI, 0.1-6.8], visceral 2.5 [95% CI, -10.4 to 17.2], and intermuscular 5.2 [95% CI, -6.6 to 18.4] fat but lower subcutaneous fat -3.5 [95% CI, -15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J-shaped pattern. Binge drinking, relative to light-to-moderate drinking, was also associated with higher ectopic fat. Conclusions Alcohol consumption had a J-shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.

Association between physical activity and clinical outcomes in high-risk hypertension: Post-hoc analysis of SPRINT.

Objective: Engaging in physical activity (PA) is recommended to reduce the risk of morbidity and mortality in patients with hypertension. However, the association between PA and clinical outcomes in individuals with high-risk hypertension is understudied. We examined the relationship between PA and clinical outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT investigated the benefit of intensive (vs. standard) blood pressure treatment in patients with high-risk hypertension. Methods: Baseline data on PA was self-reported. Vigorous-intensity PA (VPA) was categorized into 2 groups based on frequency of "Rarely or Never" and 1 or more sessions/month. Moderate-intensity PA (MPA) was also categorized into 2 groups based on average duration/day of <15 min and 15 or more minutes. Using multivariable Cox regression, we estimated the associations between PA the primary outcome which was a composite of cardiovascular events, and all-cause mortality. Results: A total of 8,320 (age 67.8 ± 9.3, 34.9% women) of SPRINT participants with data on PA were included. During a median follow-up of 3.8 years, 619 primary outcome, and 419 all-cause mortality events occurred. Compared to not engaging in VPA, the risk of the primary outcome, myocardial infarction, and all-cause mortality (HR 95% CIs) associated with VPA of ≥1sessions/month was 0.79(0.65-0.94; p=0.009), 0.70(0.52-0.93; p=0.014) and 0.75(0.60-0.94; p=0.011), respectively. Similarly, the risk of the primary outcome and all-cause mortality (HR 95% CI) associated with engaging in MPA for ≥15 min/day, relative to <15 min/day was 0.76(0.63-0.93; p=0.008) and 0.80(0.62-1.02; p=0.066), respectively. Conclusion: Among individuals with hypertension from the SPRINT study, VPA and MPA at a threshold of ≥1sessions/month and MPA of ≥15 min/day respectively, were both associated with a lower risk for cardiovascular events, and VPA was also associated with a reduced risk for all-cause mortality. Further studies are required to identify the optimal volume and intensity of PA in high-risk hypertension.

Epicardial Adipose Tissue Assessed by Computed Tomography and Echocardiography Are Associated With Adverse Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Epicardial adipose tissue (EAT) has garnered attention as a prognostic and risk stratification factor for cardiovascular disease. This study, via meta-analyses, evaluates the associations between EAT and cardiovascular outcomes stratified across imaging modalities, ethnic groups, and study protocols. METHODS: Medline and Embase databases were searched without date restriction on May 2022 for articles that examined EAT and cardiovascular outcomes. The inclusion criteria were (1) studies measuring EAT of adult patients at baseline and (2) reporting follow-up data on study outcomes of interest. The primary study outcome was major adverse cardiovascular events. Secondary study outcomes included cardiac death, myocardial infarction, coronary revascularization, and atrial fibrillation. RESULTS: Twenty-nine articles published between 2012 and 2022, comprising 19 709 patients, were included in our analysis. Increased EAT thickness and volume were associated with higher risks of cardiac death (odds ratio, 2.53 [95% CI, 1.17-5.44]; P=0.020; n=4), myocardial infarction (odds ratio, 2.63 [95% CI, 1.39-4.96]; P=0.003; n=5), coronary revascularization (odds ratio, 2.99 [95% CI, 1.64-5.44]; P<0.001; n=5), and atrial fibrillation (adjusted odds ratio, 4.04 [95% CI, 3.06-5.32]; P<0.001; n=3). For 1 unit increment in the continuous measure of EAT, computed tomography volumetric quantification (adjusted hazard ratio, 1.74 [95% CI, 1.42-2.13]; P<0.001) and echocardiographic thickness quantification (adjusted hazard ratio, 1.20 [95% CI, 1.09-1.32]; P<0.001) conferred an increased risk of major adverse cardiovascular events. CONCLUSIONS: The utility of EAT as an imaging biomarker for predicting and prognosticating cardiovascular disease is promising, with increased EAT thickness and volume being identified as independent predictors of major adverse cardiovascular events. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42022338075.

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce. METHODS: We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels. RESULTS: The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores. CONCLUSION: In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

Circulating ketone bodies and cardiovascular outcomes: the MESA study.

AIMS: Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). METHODS AND RESULTS: This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07-2.65), per 10-fold increase in total KB]. CONCLUSION: The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

Predicting short-term adverse outcomes in the geriatric population presenting with syncope: a comparison of existing syncope rules and beyond.

OBJECTIVES: Syncope at age 65+ is associated with increased mortality, irrespective of cause. Syncope rules were designed to aid in risk-stratification but were only validated in the general adult population. Our objective was to determine if they can be applied to a geriatric population in predicting short-term adverse outcomes. METHODS: In this single-center retrospective study, we evaluated 350 patients aged 65+ presenting with syncope. Exclusion criteria included confirmed non-syncope, active medical condition, drug or alcohol-related syncope. Patients were stratified into high or low risk based on Canadian Syncope Risk Score (CSRS), Evaluation of Guidelines in Syncope Study (EGSYS), San Francisco Syncope Rule (SFSR), and Risk Stratification of Syncope in the Emergency Department (ROSE). Composite adverse outcomes at 48-hour and 30-day included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), return emergency department visit, hospitalization, or medical intervention. We assessed each score's ability to predict the outcomes using logistic-regression and compared performances using receiver-operator curves. Multivariate analyses were performed to study the associations between recorded parameters and outcomes. RESULTS: CSRS outperformed with AUC of 0.732 (95% CI: 0.653-0.812) and 0.749 (95% CI: 0.688-0.809) for 48-h and 30-day outcomes, respectively. Sensitivities for CSRS, EGSYS, SFSR, and ROSE for 48-hour outcomes were 48%, 65%, 42% and 19%; and for 30-day outcomes were 72%, 65%, 30% and 55%, respectively. Atrial fibrillation/flutter on EKG, congestive heart failure, antiarrhythmics, systolic blood-pressure < 90 at triage, and associated chest pain highly correlated with 48-h outcomes. An EKG abnormality, heart disease history, severe pulmonary hypertension, BNP > 300, vasovagal predisposition, and antidepressants highly correlated with 30-day outcomes. CONCLUSIONS: Performance and accuracy of four prominent syncope rules were suboptimal in identifying high-risk geriatric patients with short-term adverse outcomes. We identified some significant clinical and laboratory information that may play a role in predicting short-term adverse events in a geriatric cohort.

Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA.

BACKGROUND: This study explored the longitudinal relationship of Lp(a) (lipoprotein[a]) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline cardiovascular disease. METHODS: Individuals from the MESA (Multi-Ethnic Study of Atherosclerosis; N=6674) were grouped as follows: group 1: Lp(a) <50 mg/dL and no hypertension; group 2: Lp(a) ≥50 mg/dL and no hypertension; group 3: Lp(a) <50 mg/dL and hypertension; and group 4: Lp(a) ≥50 mg/dL and hypertension. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to assess the relationship of Lp(a) and hypertension with time to cardiovascular disease events. RESULTS: Mean follow-up time was 13.9 (5.0) years and 809 participants experienced a cardiovascular disease event. A statistically significant interaction was found between Log[Lp(a)] and hypertension status (P=0.091). Compared with the reference group (Lp[a] <50 mg/dL and no hypertension), those with Lp[a] ≥50 mg/dL and no hypertension had no increased risk for cardiovascular disease events (hazard ratio, 1.09 [95% CI, 0.79-1.50]). However, those with Lp(a) <50 mg/dL and hypertension or Lp(a) ≥50 mg/dL and hypertension demonstrated a statistically significant increase in risk compared to the reference group (hazard ratio, 1.66 [95% CI, 1.39-1.98]) and (hazard ratio, 2.07 [95% CI, 1.63-2.62]), respectively. Among those with hypertension, Lp(a) was associated with a significant increase in cardiovascular disease risk (hazard ratio, 1.24 [95% CI, 1.01-1.53]). CONCLUSIONS: Although the major contribution to cardiovascular risk was hypertension, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease. More research is needed to understand mechanistic links among Lp(a), hypertension, and cardiovascular disease.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. However, only 80% of patients benefit from initial CBA. There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) decreases the recurrence of AF postablation, particularly in nonparoxysmal AF undergoing radiofrequency ablation. The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia (AA) following CBA for paroxysmal AF. AIM: To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF. METHODS: We followed 103 patients (age 60.6 ± 9.1 years, 29% women) with paroxysmal AF undergoing CBA 1-year post procedure. Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring. A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence. RESULTS: After a 1-year follow-up, 19 (18.4%) participants developed recurrence of AA. Use of ACEI or ARB therapy was noted in the study population. Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (P = 0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA (P = 0.2173). CONCLUSION: In our study population, preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Plasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy. METHODS: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL. The relationship of Lp(a) and LDL-C with time to CHD events was assessed with Kaplan Meier curves and multivariable Cox proportional hazard models. RESULTS: Participants were followed for a mean of 13.4 years and a total of 315 CHD events occurred. Compared to participants with LDL-C ≤ 100 mg/dL and Lp(a) < 50 mg/dL, those with LDL-C > 100 mg/dL and Lp(a) < 50 mg/dL (Group 2) demonstrated no increased risk for CHD events (HR: 0.92; 95% CI: 0.69, 1.21). However, participants with LDL-C ≤ 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 3) and those with LDL-C > 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 4) exhibited significantly increased risk of CHD events compared to Group 1 (HR: 1.83; 95% CI: 1.02, 3.27) and Group 2 (HR: 1.61; 95% CI: 1.15, 2.26), respectively. CONCLUSIONS: When Lp(a) was elevated, risk of CHD events increased, regardless of baseline LDL-C.

Association between remnant lipoprotein cholesterol, high-sensitivity C-reactive protein, and risk of atherosclerotic cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Elevated remnant-lipoprotein (RLP)-cholesterol (RLP-C) and high-sensitivity C-reactive protein (hsCRP) are each individually associated with atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To evaluate the interplay of nuclear magnetic resonance (NMR)-derived RLP-C and hsCRP and their association with ASCVD in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Lipoprotein particles were measured using NMR spectroscopic analysis at baseline. RLP-C includes very-low-density lipoprotein cholesterol and intermediate-density lipoprotein cholesterol. Four groups were created as follows: Group 1: RLP-C ≤ median (≤29.14 mg/dL) and hsCRP < 2 mg/L; Group 2: RLP-C ≤ median and hsCRP≥ 2 mg/L; Group 3: RLP-C > median and hsCRP level < 2 mg/L; and Group 4: RLP-C > median and hsCRP level ≥ 2 mg/L. Kaplan-Meier survival curves and multivariable-adjusted Cox proportional hazard models were used to examine the relationship between RLP-C and hsCRP with incident ASCVD. RESULTS: A total of 6,720 MESA participants (mean age 62.2 y, 53% female) with a median follow-up of 15.6 years were included. In the fully adjusted model, compared to those in the reference group (Group 1), participants in Group 2, Group 3, and Group 4 demonstrated a 20% (95% CI, -2%-48%), 18% (-4%-44%), and 43% (18%-76%) increased risk of incident ASCVD events, respectively (p < 0.01). An additive and multiplicative interaction between RLP-C and hsCRP was not statistically significant. CONCLUSION: NMR-derived RLP-C and hsCRP showed a similar independent association with incident ASCVD. Notably, the combination of increased RLP-C and hsCRP was associated with an increased risk of future ASCVD events.

Relationship of American Heart Association's Life Simple 7, Ectopic Fat, and Insulin Resistance in 5 Racial/Ethnic Groups.

BACKGROUND: The inverse association between ideal cardiovascular health (CVH) as measured by the American Heart Association's Life Simple 7 (LS7) and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and specific risk factors for cardiometabolic disease is sparse in diverse cohorts. METHODS: This study included 7717 participants from the Mediators of Atherosclerosis in South Asians Living in America and the Multi-Ethnic Study of Atherosclerosis cohorts. We assigned each LS7 component a 0, 1, and 2 and summed these scores to derive an overall CVH score. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Multivariable linear regression was used to examine associations between CVH categories and each log-transformed ectopic fat depot, as well as the homeostatic assessment for insulin resistance (HOMA-IR). RESULTS: In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 63.4% (95% CI, 54.3-73.0) higher visceral fat area, 84.0% (95% CI, 76.5-92.1) higher pericardial fat volume, 61.6% (95% CI, 50.7-73.2) higher subcutaneous fat area, and 40.6% (95% CI, 30.2-52.0) higher intermuscular fat area, and 15.1% (95% CI, 13.1-17.2) higher hepatic fat (all Ps < 0.001). Also, poor CVH was associated with 148.2% (95% CI, 131.1-166.7) higher HOMA-IR. We also found significant heterogeneity in the strengths of association by race/ethnicity for each ectopic fat depot. CONCLUSION: Poor and intermediate CVH, as defined by LS7 metrics, were associated with significantly higher measures of ectopic fat and insulin resistance among individuals from 5 racial/ethnic groups.

Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study.

BACKGROUND: Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). METHODS: The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. RESULTS: At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. CONCLUSIONS: Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.

Alcohol Consumption and Systemic Hypertension (from the Third National Health and Nutrition Examination Survey).

Epidemiological studies have established the association between excessive alcohol consumption and systemic hypertension (SH). However, there are conflicting reports of the association of low to moderate alcohol consumption with SH. The objective of the study was to examine the associations of alcohol consumption and blood pressure categories using the 2017 American College of Cardiology/American Heart Association high blood pressure guidelines. This analysis included 17,059 participants from the Third National Health and Nutrition Examination Survey. Alcohol consumption was ascertained by way of a questionnaire. Blood pressure (mm Hg) was measured during the in-home interview and the participant's visit to the mobile examination center. We used multivariable logistic regression models to examine cross-sectional associations of alcohol consumption and blood pressure categories based on new American College of Cardiology/American Heart Association High Blood Pressure guidelines. Models were adjusted for age, gender, income, and cardiovascular risk factors. Compared with never drinkers, moderate drinkers (7 to 13 drinks/week) had increased odds of prevalent stage 1 and stage 2 SH (odds ratio [95% confidence interval] 1.51 [1.22 to 1.87] and 1.55 [1.20 to 2.00]). Similarly, there were significantly higher odds of prevalent stage 1 and stage 2 SH among heavy drinkers (≥14 drinks/week) (odds ratio [95% confidence interval] 1.65 [1.33 to 2.05] and 2.46 [1.93 to 3.14]). We did not find any association between alcohol consumption and elevated blood pressure category. Response bias must be considered because alcohol consumption was self-reported. Our study indicates the need for further research to understand the potential mechanisms by which alcohol consumption increases the risk of SH. In conclusion, this analysis from a population-based survey showed an association between moderate and heavy alcohol consumption and a higher prevalence of SH.

Presence of a left common pulmonary vein and pulmonary vein anatomical characteristics as predictors of outcome following cryoballoon ablation for paroxysmal atrial fibrillation.

PURPOSE: Pulmonary vein (PV) isolation using cryoballoon ablation (CBA) is a common therapy for patients with drug-refractory paroxysmal atrial fibrillation (PAF). However, initial CBA is successful in only 70-80% of patients. The role of an atypical left common PV (LCPV) and PV anatomical indices on CBA outcomes remains unclear. METHODS: We followed 80 patients (age 60.7 ± 9.7, 31 % women) with PAF undergoing CBA for 1-year post-procedure for the development of recurrent atrial arrhythmias (AA). Recurrence was assessed by documented AA on EKG or any form of long-term cardiac rhythm monitoring. The presence of an LCPV and individual PV diameters were evaluated using cardiac CT. Based on the maximum and minimum PV ostial diameters, the eccentricity index (EI), ovality index (OI), and PV ostial area (PVA) were calculated for all the veins. A multivariable Cox-proportional hazard model assessed whether the presence of an LCPV or PV anatomic indices (EI, OI, and PVA) predicted recurrence of AA following CBA. RESULTS: After 1-year follow-up, 19 (23.7%) participants developed recurrence of AA. On multivariable regression, the presence of an LCPV did not predict the recurrence of AA (p = 0.38). Among the PV anatomical indices, on univariate analysis, only the area of the left inferior PV showed a trend towards predicting recurrence, though this result was not significant on multivariate analysis (p = 0.09). CONCLUSIONS: In patients with PAF, neither the presence of an LCPV nor individual PV anatomical indices predicted recurrence of AA following CBA.