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) 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.

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.

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics.

BACKGROUND: Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). RESULTS: Median age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured. CONCLUSIONS: The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Subclinical vascular composites predict clinical cardiovascular disease, stroke, and dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all-cause CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together, and adjustment for conventional risk scores for global CVD, stroke, and dementia. RESULTS: After factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, atherosclerosis, arteriosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of atherosclerosis and arteriosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. CONCLUSIONS: Subclinical vascular composites of atherosclerosis and arteriosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

Potential Mediators for Treatment Effects of Novel Diabetes Medications on Cardiovascular and Renal Outcomes: A Meta-Regression Analysis.

BACKGROUND: Prior research suggests clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are mediated by changes in glycated hemoglobin, body weight, systolic blood pressure, hematocrit, and urine albumin-creatinine ratio. We aimed to confirm these findings using a meta-analytic approach. METHODS AND RESULTS: We updated a systematic review of 9 GLP-1RA and 13 SGLT2i trials and summarized longitudinal mediator data. We obtained hazard ratios (HRs) for cardiovascular, renal, and mortality outcomes. We performed linear mixed-effects modeling of LogHRs versus changes in potential mediators and investigated differences in meta-regression associations among drug classes using interaction terms. HRs generally became more protective with greater glycated hemoglobin reduction among GLP-1RA trials, with average HR improvements of 20% to 30%, reaching statistical significance for major adverse cardiovascular events (ΔHR, 23%; P=0.02). Among SGLT2i trials, associations with HRs were not significant and differed from GLP1-RA trials for major adverse cardiovascular events (Pinteraction=0.04). HRs for major adverse cardiovascular events, myocardial infarction, and stroke became less efficacious (ΔHR, -15% to -34%), with more weight loss for SGLT2i but not for GLP-1RA trials (ΔHR, 4%-7%; Pinteraction<0.05). Among 5 SGLT2i trials with available data, HRs for stroke became less efficacious with larger increases in hematocrit (ΔHR, 123%; P=0.09). No changes in HRs by systolic blood pressure (ΔHR, -11% to 9%) and urine albumin-creatinine ratio (ΔHR, -1% to 4%) were found for any outcome. CONCLUSIONS: We confirmed increased efficacy findings for major adverse cardiovascular events with reduction in glycated hemoglobin for GLP1-RAs. Further research is needed on the potential loss of cardiovascular benefits with increased weight loss and hematocrit for SGLT2i.

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.

Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Postmenopausal Women.

BACKGROUND: Sex hormone (SH) imbalances have been linked to a higher risk of heart failure in both sexes. However, mechanisms that underlie this relationship remain unclear. We examined the association of baseline SH with interstitial and replacement myocardial fibrosis in the MESA (Multi-Ethnic Study of Atherosclerosis) using cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement (LGE). OBJECTIVES: The purpose of this study was to assess the link between baseline sex hormone levels and myocardial fibrosis in the MESA cohort using CMR. METHODS: A total of 2,324 participants (men and postmenopausal women [PMW]) were included in the MESA with SH measured at baseline and had underwent CMR 10 years later. All analyses were stratified by sex and age. Regression models were constructed to assess the associations of baseline SH with extracellular volume (ECV)% and native T1 time and with LGE. Higher native T1 time and ECV% are interpreted as evidence of increasing interstitial myocardial fibrosis (IMF). Given the limited number of myocardial scars present in PMW, analysis of LGE was limited to men. RESULTS: Among older men (age ≥65 years), a 1-SD increment higher free testosterone was significantly associated with 2.45% lower ECV% and 21.5% lower native T1 time, while a 1-SD increment higher bioavailable testosterone was associated with 12.5% lower native T1 time. A 1-SD increment greater sex hormone-binding globulin level was associated with 1% higher ECV%. Among PMW of 55 to 64 years, a 1-SD increment higher total testosterone was associated with 9.5% lower native T1 time. Higher levels of estradiol in older men were independently associated with higher odds of having a myocardial scar (OR: 4.10; 95% CI: 1.35-12.40; P = 0.01). CONCLUSIONS: Among older men, SH imbalances at initial evaluation were independently associated with CMR defined IMF and replacement fibrosis, respectively; while increasing total testosterone in middle-aged PMW was associated with lesser marker of IMF. (JACC Adv 2023;2:100320) Published by Elsevier on behalf of the American College of Cardiology Foundation.

Electrocardiographic Associations of Cardiac Biomarkers and Cardiac Magnetic Resonance Measures of Fibrosis in the Multiethnic Study of Atherosclerosis (MESA).

Abnormalities in myocardial substrate, including diffuse and replacement fibrosis, increase the risk of cardiovascular disease (CVD). Data are sparse on whether electrocardiogram (ECG) measures, coupled with circulating biomarkers, may aid in identifying cardiac fibrosis. This study aimed to determine whether 12-lead ECG and biomarkers together augment the prediction of cardiac fibrosis in participants who are free of known CVD. This is a cross-sectional analysis in the MESA (Multiethnic Study of Atherosclerosis) study at visit 5 (2010 to 2012), with measurements of biomarkers (cardiac troponin T and growth differentiation factor-15), gadolinium-enhanced cardiac magnetic resonance imaging, and ECG. Logistic regression associations of ECG measures with cardiac magnetic resonance surrogates of fibrosis (highest quartile extracellular volume [interstitial fibrosis] and late gadolinium enhancement [replacement fibrosis]) were adjusted for demographics and risk factors. Using the C-statistic, we evaluated whether adding ECG measures and biomarkers to clinical characteristics improved the prediction of either type of fibrosis. There were 1,170 eligible participants (aged 67.1 ± 8.6 years). Among the ECG measures, QRS duration (odds ratio [OR] 1.41 per 10 ms, 95% confidence interval [CI] 1.10 to 1.81), major ST-T abnormalities (OR 3.03, 95%CI 1.20, 7.65), and abnormal QRS-T angle (OR 6.32, 95%CI 3.00, 13.33) were associated with replacement fibrosis, whereas only abnormal QRS-T angle (OR 3.05, 95%CI,1.69, 5.48) was associated with interstitial fibrosis. ECG markers, in addition to clinical characteristics, improved the prediction of replacement fibrosis (p = 0.002) but not interstitial fibrosis. The addition of cardiac troponin T and growth differentiation factor-15 to the ECG findings did not significantly improve the model discrimination for either type of cardiac fibrosis. In CVD free participants, simple ECG measures are associated with replacement fibrosis and interstitial fibrosis. The addition of these measures improves identification of replacement but not interstitial fibrosis. These findings may help refine the identification of myocardial scar in the general population.

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. OBJECTIVE: Characterize the relationship between SMI on ECG and CAC. METHODS: Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. RESULTS: Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). CONCLUSION: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

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.

Implications of Social Disadvantage Score in Cardiovascular Outcomes and Risk Assessment: Findings From the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Social determinants of health contribute to disparate cardiovascular outcomes, yet they have not been operationalized into the current paradigm of cardiovascular risk assessment. METHODS: Data from the Multi-Ethnic Study of Atherosclerosis, which includes participants from 6 US field centers, were used to create an index of baseline Social Disadvantage Score (SDS) to explore its association with incident atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality and impact on ASCVD risk prediction. SDS, which ranges from 0 to 4, was calculated by tallying the following social factors: (1) household income less than the federal poverty level; (2) educational attainment less than a high school diploma; (3) single-living status; and (4) experience of lifetime discrimination. Cox models were used to examine the association between SDS and each outcome with adjustment for traditional cardiovascular risk factors. Changes in the discrimination and reclassification of ASCVD risk by incorporating SDS into the pooled cohort equations were examined. RESULTS: A total of 6434 participants (mean age, 61.9±10.2 years; female 52.8%; non-white 60.9%) had available SDS 1733 (26.9%) with SDS 0; 2614 (40.6%) with SDS 1; 1515 (23.5%) with SDS 2; and 572 (8.9%) with SDS ≥3. In total, 775 incident ASCVD events and 1573 deaths were observed over a median follow-up of 17.0 years. Increasing SDS was significantly associated with incident ASCVD and all-cause mortality after adjusting for traditional risk factors (ASCVD: per unit increase in SDS hazard ratio, 1.15 [95% CI, 1.07-1.24]; mortality: per unit increase in SDS hazard ratio, 1.13 [95% CI, 1.08-1.19]). Adding SDS to pooled cohort equations components in a Cox model for 10-year ASCVD risk prediction did not significantly improve discrimination (P=0.208) or reclassification (P=0.112). CONCLUSIONS: Although SDS is independently associated with incident ASCVD and all-cause mortality, it does not improve 10-year ASCVD risk prediction beyond pooled cohort equations.

Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression.

BACKGROUND: Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear. PURPOSE: To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression. DATA SOURCES: We performed a systematic review using PubMed through 7 November 2022. STUDY SELECTION: We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data. DATA EXTRACTION: Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes. DATA SYNTHESIS: We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant. LIMITATIONS: Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials. CONCLUSIONS: Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.

Subclinical Vascular Composites Predict Clinical Cardiovascular Disease, Stroke, and Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6,814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supine blood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together and adjustment for conventional risk scores for global CVD, stroke, and dementia. Results: After factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, arteriosclerosis, atherosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of arteriosclerosis and atherosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. Conclusions: Subclinical vascular composites of arteriosclerosis and atherosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

Relationship between abnormal P-wave axis, chronic obstructive pulmonary disease and mortality in the general population.

BACKGROUND: It is unclear whether the presence of a vertical P-wave axis on electrocardiogram modifies the association of COPD with mortality. OBJECTIVE: To examine the association and interaction of abnormal P-wave axis and COPD with mortality. STUDY DESIGN AND METHODS: The analysis included 7359 with ECG data from the Third National Health and Nutrition Examination Survey (NHANES-III) who were free of cardiovascular disease (CVD) at enrollment. Abnormal P-wave axis (aPWA) was defined as values above 75°. COPD was self-reported as either a diagnosis of emphysema or chronic bronchitis. National Death Index was used to identify the date of death and cause of death. Using multivariable Cox proportional hazard analysis, we examined the association of COPD with all-cause mortality by aPWA status. RESULTS: Over a median follow-up of 14 years, 2435 deaths occurred. Participants with concomitant presence of aPWA and COPD experienced higher death rates (73.9 per 1000 person-years (PY)) compared to either COPD or aPWA alone (36.4 per 1000 PY and 31.1 per 1000 PY), respectively. In multivariable-adjusted models, a stronger association between COPD and mortality was noted in the presence compared to the absence of aPWA (HR 95% CI): 1.71 (1.37-2.13) vs. 1.22(1.00-1.49), respectively (interaction P-value = 0.02). Similarly, a stronger association between aPWA and mortality was observed in the presence compared to the absence of COPD (HR 95% CI): 1.66(1.26-2.19) vs. 1.18(1.06-1.31), respectively (interaction P-value = 0.02). Similar higher death rates and mortality risk was observed when spirometry-confirmed COPD and aPWA were present together than in isolation. CONCLUSION: The concomitant presence of aPWA and COPD leads to a significantly higher mortality rate compared to the presence either COPD or aPWA alone as a clinical variable. P-wave axis, reported routinely on ECG printout, can potentially identify patients with COPD who need intensive control of risk factors and disease management.

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.

Cardiac Structure and Function Phenogroups and Risk of Incident Heart Failure (from the Multi-ethnic Study of Atherosclerosis).

Indices of cardiac structure and function, such as left ventricular (LV) mass and ejection fraction, have been associated with risk of incident heart failure (HF), but the clinical relevance of data-driven grouping of a comprehensive set of cardiac parameters is unclear. In Multi-Ethnic Study of Atherosclerosis participants, latent class analysis was applied in the sample stratified by gender to define phenogroups on the basis of cardiovascular magnetic resonance imaging parameters of right ventricular and LV structure and function at baseline. Cox proportional hazard models in gender-stratified analyses were used to assess the association between phenogroup membership and risk of HF subtypes adjusting for potential confounders. In the 4,204 participants (mean age 61 ± 10 years, 53% women), the mean follow-up time was 14 ± 4 years for men and 15 ± 4 years for women. For both genders, 4 distinct phenogroups were identified: (1) ideal cardiac mechanics; (2) higher output/hypertrophied LV; (3) impaired ejection fraction/dilated LV; and (4) higher output/hyperdynamic (LV). Men in phenogroups 4 (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.60 to 5.31, p = 0.0005), 3 (HR 3.52, 95% CI 1.90 to 6.53, p <0.0001), and 2 (HR 3.49, 95% CI 1.94 to 6.28, p <0.0001) had higher rates of incident HF than did men in phenogroup 1, in fully adjusted models. No significant associations were found between phenogroup membership and incident HF in women. In conclusion, phenogroup membership based on cardiac structure and function in men was significantly associated with incident HF. Integration of cardiac magnetic resonance imaging variables may help identify differential risk for HF in men.

Relation of Left Ventricular Hypertrophy Subtype to Long-Term Mortality in Those With Subclinical Cardiovascular Disease (from the Multiethnic Study of Atherosclerosis [MESA]).

The clinical and biochemical profile of differing Left ventricular hypertrophy phenotypes and its effect on long-term outcomes is ill-defined. The study investigated the differences in risk profiles and prognostic effect of concentric (CH) and eccentric hypertrophy (EH) on long-term adverse outcomes in a contemporary, ethnically diverse cohort. We analyzed follow-up data over 15 years from the Multiethnic Study of Atherosclerosis study. A total of 4,979 participants with cardiac magnetic resonance performed at baseline enrollment were included. Descriptive statistics, Kaplan-Meier curves, and regression models were applied. Independent variables associated with CH were black and Hispanic race/ethnicity, systolic blood pressure, and metabolic syndrome. Independent variables associated with EH were systolic blood pressure and urine creatinine, whereas serum creatinine had an inverse association. The primary end point of all-cause death (n = 1,137, 22.8%) occurred in 21.7%, 47.4%, and 56.6% of participants with no, CH, or EH, respectively (p- < 0.001). Age (hazard ratio [HR] per year = 1.10 [1.09 to 1.11], p <0.001), male gender (HR = 1.48 [1.29 to 1.69], p <0.001), black race (HR = 1.17 [1.005 to 1.36], p = 0.04), fasting glucose (HR = 1.005 [1.003 to 1.007], p <0.001), baseline creatinine (HR per mg/100 ml = 1.29 [1.15 to 1.46], p <0.001), left ventricular ejection fraction (HR per 1% = 0.98 [0.98 to 0.99], p = 0.005), IL-6 (HR per pg/ml = 1.17 [1.12 to 1.22], p <0.001), CH (HR = 1.84 [1.41 to 2.41], p <0.001), and EH (HR = 2.58 [1.77 to 3.76], p <0.001) were significant predictors of all-cause mortality. In conclusion, CH and EH are 2 distinct clinical phenotypes of left ventricular hypertrophy with differing gender and racial predisposition, both of which are associated with worse long-term adverse outcomes.

The Interplay of Race/Ethnicity and Obesity on the Incidence of Venous Thromboembolism.

INTRODUCTION: Factors predisposing asymptomatic individuals within the community to venous thromboembolism are not fully understood. This study characterizes the incidence and determinants of venous thromboembolism among the Multiethnic Study of Atherosclerosis cohort with a focus on race/ethnicity and obesity. METHODS: This study (analyzed in 2020-2021) used the Multiethnic Study of Atherosclerosis cohort (2000-2017), which included participants with diverse ethnic/racial backgrounds aged 45-84 years without cardiovascular disease at baseline. The primary endpoint was time to diagnosis of venous thromboembolism defined using International Classification of Diseases codes (415, 451, 453, 126, 180, and 182). Multivariable-adjusted hazard ratios of the predictors of venous thromboembolism were calculated with a focus on the interaction between obesity and race/ethnicity categories. RESULTS: Over a median follow-up period of 14 years, 233 individuals developed venous thromboembolism. Incidence rates (per 1,000 person-years) varied across racial/ethnic groups with the highest incidence among Black (4.02) followed by White (2.98), Hispanic (2.08), and Chinese (0.79) participants. There was a stepwise increase in the incidence rate of venous thromboembolism with increasing BMI regardless of race/ethnicity: normal (1.95), overweight (2.52), obese (3.63), and morbidly obese (4.55). The association between BMI and venous thromboembolism was strongest among non-White women with the highest incidence rate for obese (4.8) compared with non-obese (1.6). The interaction among obesity, gender, and race was statistically significant (p=0.01) in non-White obese women. Risk of venous thromboembolism increased with age for all race/ethnicities. CONCLUSIONS: This study finds that obesity may confer an increased risk for venous thromboembolism among non-White women compared with other groups-White men, White women, and non-White men.