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Little is known about the relationships between annual visit-to-visit blood pressure variability and heart failure subphenotypes. The aim of this analysis was to examine the association between blood pressure variability and incident heart failure with preserved and reduced ejection fraction.Data from 23,918 postmenopausal women enrolled in the Women's Health Initiative Hormone Therapy Trials were analyzed. Blood pressure was measured at baseline (1993‒1998) and then annually through 2005. Variability was defined as the SD of the mean blood pressure across visits or the SD of the participant's regression line for blood pressure across visits. The outcome was the first heart failure hospitalization. Heart failure ascertainment and adjudications were through March 31, 2018.During a mean follow-up of 15.8 years, 913 incident cases of heart failure with preserved ejection fraction and 421 cases of heart failure with reduced ejection fraction were identified. In fully adjusted models, including mean longitudinal systolic and diastolic blood pressure and time-varying coronary events interim to heart failure hospitalization, women in the highest versus in the lowest quartile of SD of the mean systolic blood pressure were at a statistically significantly higher risk of heart failure with preserved ejection fraction (hazard ratio [95% CI]=1.61 [1.12, 2.31]) but not of heart failure with reduced ejection fraction (1.18 [0.70,1.96]). Conversely, the hazard ratio (95% CI) for the highest versus lowest quartile of SD of the mean diastolic blood pressure was 1.56 (0.89, 2.74) for heart failure with reduced ejection fraction and 1.19 (0.85,1.65) for heart failure with preserved ejection fraction. Results attenuated for SD of the participant's regression line when additionally adjusted for the temporal trend of systolic and diastolic blood pressure.Greater systolic blood pressure variability was associated with a higher risk of heart failure with preserved ejection fraction independent of mean blood pressure and coronary events interim to heart failure hospitalization.

Purpose of Review Clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel cardiovascular risk factor. Here we review the relationship of lifestyle and environmental risk factors predisposing to somatic mutations and CHIP and provide an overview on age-related cardiovascular outcomes. Recent Findings CHIP has been associated with accelerated atherosclerosis and cardiovascular disease in both epidemiological and experimental studies. The most commonly mutated candidate driver genes are DNMT3A, TET2, JAK2, and ASXL1. The underlying mechanisms appear predominantly related to inflammatory pathways. Although age is the dominant risk factor for developing CHIP, emerging evidence suggests that other factors such as smoking, obesity/type 2 diabetes, or an unhealthy diet play a role in the occurrence of somatic mutations. Summary Evidence suggests a strong link between vascular risk factors, somatic hematopoietic mutations, and age-related cardiovascular disease. Further studies on CHIP biology are required to identify targeted interventions for risk reduction in patients with CHIP and inform the utility of screening strategies.

Background Recommended systolic blood pressure targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause mortality in older women in the Women’s Health Initiative Long Life Study (WHI-LLS). Methods The study sample included 7,875 women (mean age: 79 years) who underwent a blood pressure measurement at an in-person home visit conducted in 2012–2013. CVD and all-cause mortality were centrally adjudicated. Hazard ratios (HRs) were obtained from adjusted Cox proportional hazards models. Results After 5 years follow-up, all-cause mortality occurred in 18.4% of women. Compared with a DBP of 80 mm Hg, the fully adjusted HR for mortality was 1.33 (95% confidence interval [CI]: 1.04–1.71) for a DBP of 50 mm Hg and 1.67 (95% CI: 1.29–2.16) for a DBP of 100 mm Hg. The HRs for CVD were 1.14 (95% CI: 0.78–1.67) for a DBP of 50 mm Hg and HR 1.50 (95% CI: 1.03–2.17) for a DBP of 100 mm Hg. The nadir DBP associated with lowest mortality risk was 72 mm Hg overall. Conclusions In older women, consideration should be given to the potential adverse effects of low and high DBP. Low DBP may serve as a risk marker. DBP target levels between 68 and 75 mm Hg may avoid higher mortality risk.

Introduction: Over 50% of US adults older than 75 live free of atherosclerotic cardiovascular disease (ASCVD) and diabetes (DM), yet data on incident statin use among this population are lacking. Our objective was to assess statin initiation by age among the Women’s Health Initiative cohort free of ASCVD and DM at baseline (1993). Hypothesis: Statin initiation is higher at older ages and differs by race/ethnicity. Methods: Exclusions were statin use at baseline, known ASCVD, DM, and no follow-up after baseline. Self-reported medication use was assessed in 1996 and 2008. Specific statin and dose prescribed at the time of initiation were identified using National Drug Codes and determined statin intensity, defined by the ACC/AHA guidelines. We estimated the adjusted association between age group ( Results: Over 12 years of follow-up, 27% of 99,631 women free of ASCVD and DM at baseline initiated a statin; initiation was lower with older age (Table). This association remained after adjustment for ASCVD risk factors and did not differ by race/ethnicity (p for interaction >0.5). Moderate intensity dose was most common at statin initiation overall, and moderate and high intensity dose were both lower with older age. Conclusion: Of women free of ASCVD and DM, women older than 75 were least likely to start a statin and most likely to start low intensity statin therapy at initiation than younger women. We identified a potential clinical gap for investigation: whether lower overall use of statins and lower intensity statin therapy among older women are associated with preventable ASCVD.

BACKGROUND AND AIMS: Various food groups have been associated with measures of left ventricular geometry and function. Whether the Dietary Approaches to Stop Hypertension (DASH) dietary pattern in mid-life is associated with a favorable cardiac structure and function later in life is unknown. METHODS AND RESULTS: The study population consisted of the Atherosclerosis Risk in Communities study participants free of cardiovascular disease at study visit 3 in 1993 to 1995. Dietary intake was assessed by food frequency questionnaire at study visits 1 (1987–1989) and 3 (1993–1995). Participants who underwent transthoracic echocardiograms at the Jackson field center at visit 3 (n=1,974) and at all field centers at study visit 5 (2011–2013; n=4,651) were included in this study. General linear regression was used to evaluate associations between dietary intake and markers of cardiac structure and function adjusting for potential confounders. Higher DASH score was associated with lower left ventricle mean wall thickness and higher absolute value of longitudinal strain at visit 5 (p(trend)=0.004 and

Background Cardiac tumours are rare but affected patients may present with symptoms mimicking other cardiac diseases. The most frequent symptoms include heart failure, arrhythmias, or embolic phenomena. Case summary A 39-year-old man with a history of extranodal NK/T-cell lymphoma of the nasal type (ENKTL-NT) in clinical remission presented at our department with incessant ventricular tachycardia. The arrhythmia could only be controlled with a combination of intravenously administered beta-blockers, ajmaline, and amiodarone. Diagnostic workup excluded ischaemia, but imaging revealed a tumour located in the apex of the left ventricle. Endomyocardial biopsy confirmed the diagnosis of cardiac relapse of ENKTL-NT. Upon chemotherapy no further arrhythmias developed. Discussion Many malignancies can metastasize into the heart. Multimodal imaging including echocardiography, cardiac magnetic resonance imaging, and a positron-emission tomography computed tomography paved the way to the diagnosis that was finally established by endomyocardial biopsy. In the present case, a cardiac metastasis from an ENKTL-NT presented with incessant ventricular tachycardia.

The potential role of nutritional factors in the development of peripheral arterial disease (PAD) remains poorly understood. We evaluated multiple recommended eating patterns as reflected by predefined diet quality indices in relation to long-term risk of PAD. We included 138 506 US postmenopausal women in the Women’s Health Initiative who had no known PAD at baseline (1993–1998). Four diet quality indices, including alternate Mediterranean diet index, alternate Healthy Eating Index-2010, Dietary Approaches to Stop Hypertension diet index, and Healthy Eating Index-2015, were derived using dietary information collected by a validated food frequency questionnaire at baseline. Incident cases of symptomatic PAD in the lower extremities were ascertained and adjudicated through March 2019 via medical record review. During a median 18.6 years of follow-up, 1036 incident PAD cases were identified. After multivariable adjustment, all diet quality scores were significantly and inversely associated with 21% (for alternate Healthy Eating Index 2010) to 34% (for Dietary Approaches to Stop Hypertension index) lower risk of PAD when comparing the highest with the lowest quartiles (all P -for-trend values ≤0.010). Among contributing food groups and nutrients, intakes of legumes, dietary fiber, and vegetable protein were associated lower risk of PAD, while intakes of unprocessed red meat, processed meat, and regular soft drinks were associated with higher risk. In a broad sample of US postmenopausal women, adhering to different recommended eating patterns is associated with lower risk of PAD. Our findings suggest that current clinical and public health strategies that recommend healthful eating patterns may also be applicable to PAD prevention.

Prior studies examined associations between Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction.Our objective was to test associations between biomarker-calibration of food frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) among Women's Health Initiative (WHI) participants. WHI is registered at clinicaltrials.gov: NCT00000611.Data were derived from WHI postmenopausal women (n = 100,374) aged 50-79 y at enrollment (1993-1998) at 40 US clinical centers, linked to nutritional biomarker substudies and outcomes over subsequent decades of follow-up. Baseline or year 1 FFQ-derived HEI-2010 scores were calibrated with nutritional biomarkers and participant characteristics [e.g., body mass index (BMI)] for systematic measurement error correction. Calibrated data were then used in hazard ratio (HR) models examining associations with incidence of CVD (total, subtypes, mortality), cancer (total, subtypes, mortality), and T2D in WHI participants with approximately two decades of follow-up. Models were multivariable-adjusted with further adjustment for BMI and doubly-labeled water (DLW)-calibrated energy.Multivariable adjusted HRs modeled a 20% increment in HEI-2010 score in relation to outcomes. HRs were modest using uncalibrated HEI-2010 scores (HRs = 0.91-1.09). Using biomarker calibrated HEI-2010, 20% increments in scores yielded multivariable-adjusted HRs (95%CIs) of: 0.75 (0.60-0.93): coronary heart disease; 0.75, (0.61.-0.91): myocardial infarction; 0.96 (0.92-1.01): stroke; 0.88 (0.75-1.02): CVD mortality; 0.81 (0.70-0.94): colorectal cancer; 0.81 (0.74-0.88): breast cancer; 0.79 (0.73-0.87): cancer mortality; and 0.45 (0.36-0.55): T2D. Except for cancer mortality and T2D incidence, results became null when adjusted for DLW-calibrated energy intake and BMI.Biomarker calibration of FFQ-derived HEI-2010 was associated with lower CVD and cancer incidence and mortality and lower T2D incidence in postmenopausal women. Attenuation after adjustment with BMI and DLW-calibrated energy suggest that energy intake and/or obesity are strong drivers of diet-related chronic disease risk in postmenopausal women.

BackgroundThe potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.ObjectivesWe aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.MethodsWe included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.ResultsA total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend=0.004) and all-cause mortality (P-trend&nbsp

Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H 2 receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large‐scale WHI (Women’s Health Initiative) study. Methods and Results This study included postmenopausal women from the WHI without a history of HF at baseline. HF was defined as first incident hospitalization for HF and physician adjudicated. Multivariable Cox proportional hazards regression models evaluated the association of H2RA use as a time‐varying exposure with HF risk, after adjustment for demographic, lifestyle, and medical history variables. Sensitivity analyses examined (1) risk of HF stratified by the ARIC (Atherosclerosis Risk in Communities) score, (2) propensity score matching on H2RA use, (3) use of proton pump inhibitors rather than H2RA nonuse as the referent, and (4) exclusion of those taking diuretics at baseline. The primary analysis included 158 854 women after exclusion criteria, of whom 9757 (6.1%) were H2RA users. During median 8.2 years of follow‐up, 376 H2RA users (4.9 events/1000 person‐years) and 3206 nonusers (2.7 events/1000 person‐years) developed incident HF. After multivariable adjustment, there was no association between H2RA use and HF in the primary analysis (hazard ratio, 1.07; 95% CI, 0.94–1.22; P =0.31) or in any of the sensitivity analyses. Conclusions Clinical H2RA use was not associated with incident HF among postmenopausal women. Future studies are needed to evaluate potential effect modification by sex, HF severity, or patterns of use on H2RA exposure and HF risk. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00000611.

Rethinking the Association of Physical Performance with Blood Pressure Changes in Older Women: Findings form the Women’s Health Initiative Background: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods: 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65-69 y; 70-79 y). Results: Overall, each z-score unit increment in grip strength was associated with 0.54 mmHg (95% CI 0.06, 1.03) higher SBP, and 0.34 mmHg (95% CI 0.07, 0.62) higher DBP ( Table 1 ). In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.74; 95% CI 0.16-1.32), among antihypertensive medication users (0.89; 95% CI 0.41, 1.37) and non-users (0.35; 95% CI 0.01, 0.68), and in those aged 65-69 y (0.64; 95% CI 0.04, 1.23). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70-79 y. Associations between any performance measure and pulse pressure change were not significant. Conclusion: These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age. Total characters with table: 2,213 Table 1

Objective To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. Summary of background data Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women. Methods This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017. Results Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early menarche. Women with premature menopause were more likely to be overweight, Black, have ≥20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA. Conclusions This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.

Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H

Background This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65–69 y; 70–79 y). Results Overall, each z-score unit increment in grip strength was associated with 0.59 mmHg (95% CI 0.10, 1.08) higher SBP, and 0.39 mmHg (95% CI 0.11, 0.67) higher DBP. In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.81; 95% CI 0.23–1.39), among antihypertensive medication users (0.93; 95% CI 0.44, 1.41) and non-users (0.37; 95% CI 0.03, 0.71), and in those aged 65–69 y (0.64; 95% CI 0.04, 1.24). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70–79 y. Associations between any performance measure and pulse pressure change were not significant. Conclusion These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age.

Acute chest pain is one of the most important cardinal symptoms in medicine. There are several important differential diagnoses for chest pain. Therefore, a thorough history and physical examination, as well as the 12-lead ECG and laboratory tests are crucial. In clinical practice, it is useful to distinguish between cardiac chest pain and other forms of chest pain in order to treat patients appropriately and to exclude potentially life-threatening conditions.

Objective: Individuals with elevated systolic blood pressure (BP) or low diastolic BP, whether or not on antihypertensive treatment, may be at higher risk for developing glaucoma. We aimed to investigate BP levels in relation to risk of incident glaucoma in a large cohort of elderly women. Methods: Prospective follow-up of 101,447 postmenopausal women without prior history of glaucoma enrolled in the Women’s Health Initiative Study (WHI). Blood pressure was measured in-clinic at baseline and after 3 years using standardized procedures and average BP was calculated. Antihypertensive medication use was determined by drug inventory at baseline and year 3. Women self-reported incident newly diagnosed glaucoma annually. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards analyses adjusting for demographic, medical history, and lifestyle covariates. Results: During a mean follow-up of 4.7 years, we documented 7,514 glaucoma cases. Among women not on antihypertensive treatment, those with systolic BP ≥140 mmHg or diastolic BP ≥80 mmHg were not at higher risk of developing glaucoma (HR 0.97, 95% CI 0.88-1.08 and HR 1.00 [0.93-1.08], respectively), compared to women with a systolic BP Conclusions: BP control is not associated with an increased or decreased glaucoma risk in elderly women.

Acute chest pain is one of the most important cardinal symptoms in medicine. There are several important differential diagnoses for chest pain. Therefore, a thorough history and physical examination, as well as the 12-lead ECG and laboratory tests are crucial. In clinical practice, it is useful to distinguish between cardiac chest pain and other forms of chest pain in order to treat patients appropriately and to exclude potentially life-threatening conditions.

Zusammenfassung Anamnese und klinischer Befund Eine 75-jährige Patientin wurde wegen akuter Übelkeit, Völlegefühl, Erbrechen ohne Blutbeimengung und unspezifischer abdomineller Schmerzsymptomatik nächtlich aufgenommen. In der Anamnese fand sich neben einem Vorhofflimmern, weswegen sie vollantikoaguliert war, ein Z. n. Schrittmacheranlage sowie eine diastolische Herzinsuffizienz. Untersuchungen und Diagnose Im Röntgenbild des Thorax fiel eine die Kalkspange des Aortenbogens umgebende Transparenzminderung auf. Eine CT-Angiografie erbrachte den Nachweis eines intramuralen Hämatoms (IMH) der Aorta vom Abgang der A. subclavia links bis nach abdominell zum Abgang der A. mesenterica inferior mit fokalen Ulzerationen. Therapie und Verlauf Da sich das IMH auf die Aorta descendens beschränkte, wurde zunächst ein konservatives Vorgehen mit blutdrucksenkenden Maßnahmen gewählt. Die Beschwerdesymptomatik der Patientin verbesserte sich trotz medikamentöser Therapie nicht. Aufgrund des komplizierten Verlaufs wurde nach interdisziplinärer Fallbesprechung eine transfemorale endovaskuläre Reparatur der Aorta mittels Stentgraft-Prothese durchgeführt. Postinterventionell erholte sich die Patientin gut von dem Eingriff, war beschwerdefrei und konnte entlassen werden. Folgerung Entscheidend für das Management eines IMH ist eine zeitnahe Diagnose und die korrekte Klassifizierung der Ausdehnung (Typ Stanford A oder Stanford B). Während für ein IMH Typ Stanford A die Indikation zur chirurgischen Versorgung gegeben ist, ist bei Typ Stanford B eine interdisziplinäre Falldiskussion sinnvoll. Bei Vorliegen eines unkomplizierten IMH ist ein konservatives Prozedere mit adäquater Einstellung einer arteriellen Hypertonie empfohlen. Bei komplizierten Verläufen sollte die endovaskuläre Therapie (Thoracic Endovascular Repair/TEVAR) als Versorgungsmöglichkeit erwogen werden.

ObjectiveTo examine the relationship between blood pressure (BP) variability (BPV), brain volumes, and cognitive functioning in postmenopausal women with few modifiable cardiovascular risk factors.MethodsStudy participants consisted of postmenopausal women enrolled in the Women's Health Initiative Memory MRI study (WHIMS-MRI) without cardiovascular disease, diabetes mellitus, hypertension, or current smoking at baseline (1996–1999). BP readings were taken at baseline and each annual follow-up visit. BPV was defined as the SD associated with a participant's mean BP across visits and the SD associated with the participant's regression line with BP regressed across visits. Brain MRI scans were performed between 2004 and 2006. Cognitive functioning was assessed at baseline and annually thereafter with the Modified Mini-Mental State Examination (3MSE) scoring until 2008. The final sample consisted of 558 women (mean age 69 years, median follow-up time [interquartile range] 8 [0.8] years).ResultsIn adjusted models including mean systolic BP, women in the highest tertile of systolic BPV had lower hippocampal volumes and higher lesion volumes compared to women in the lowest tertile. No relationship between BPV and 3MSE scoring was detected.ConclusionsIn postmenopausal women with few modifiable cardiovascular risk factors, greater visit-to-visit systolic BPV was associated with reductions in hippocampal volume and increases in lesion volumes at later life. These data add evidence to the emerging importance of BPV as a prognostic indicator even in the absence of documented cardiovascular risk factors.

Introduction: Little is known about the relationships between visit-to-visit BPV and HF sub-phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The aim of this analysis was to investigate the relationship of visit-to-visit systolic and diastolic BPV and risk of HF subtypes HFrEF and HFpEF in a large cohort of postmenopausal women. Hypothesis: We hypothesized that greater systolic and diastolic BPV would be associated with a higher risk for HFrEF and HFpEF. Methods: This study consisted of 23,918 postmenopausal women aged 50-79 enrolled in the Women’s Health Initiative Hormone Therapy Trials. Blood pressure (BP) was measured at baseline (1993-1998) and then annually through 2005 by trained clinical staff. Variability was defined as the standard deviation of the mean BP across visits (SDm). The outcome was first HF hospitalization, which was adjudicated by physician review of medical records. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for HF endpoints with adjustments for demographic, medical history, lifestyle factors, antihypertensive medication use, mean systolic and diastolic BPs, and time-varying coronary events interim to HF hospitalization. Results: During a mean follow-up of 15.8 years, 913 incident cases of HFpEF and 421 cases of HFrEF were identified. In fully adjusted models, women in the highest quartile of SDm for systolic blood pressure were at higher risk of HFpEF [HR (95% CI): 1.61, 95% confidence interval: 1.12, 2.31)], but not HFrEF [1.18 (0.70,1.96)] compared to women in the lowest quartile of SDm. Higher SDm for diastolic blood pressure was not related to HFpEF [1.19 (0.85,1.65)] or HFrEF [1.56 (0.89,2.74)]. Conclusions: Greater systolic BPV was associated with a higher risk of HFpEF independent of mean blood pressure and coronary events interim to HF hospitalization. These findings suggest that control of BPV may be a relevant target for the prevention of HFpEF in postmenopausal women.

Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women’s Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person‐years of follow‐up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all‐cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all‐cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 [1.02, 1.19]). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 [1.05, 1.32]), while consumption of poultry (HR, 0.85 [0.75, 0.97]) or eggs (HR, 0.86 [0.75, 0.98]) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all‐cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all‐cause mortality. Conclusions Different dietary protein sources have varying associations with all‐cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.

Few studies have evaluated hypertension incidence in relation to walking, which is a common physical activity among adults. We examined the association between walking and hypertension incidence in 83 435 postmenopausal women who at baseline were aged 50 to 79 years, without known hypertension, heart failure, coronary heart disease, or stroke, and reported the ability to walk at least one block without assistance. Walking volume (metabolic equivalent hours per week) and speed (miles per hour) were assessed by questionnaire. Incident physician-diagnosed hypertension treated with medication was ascertained through annual questionnaires. During a mean 11-year follow-up, 38 230 hypertension cases were identified. After adjustment for covariates including nonwalking activities, a significant inverse association with hypertension was observed across categories of baseline walking volume (0 [referent], >0–3.5, 3.6–7.5, and >7.5 metabolic equivalent hours per week), hazard ratio: 1.00 (referent), 0.98, 0.95, 0.89; trend P 4 miles per hour) also were associated with lower hypertension risk, hazard ratio: 1.00 (referent), 1.07, 0.95, 0.86, 0.79; trend P P 7.5 metabolic equivalent hours per week) and at faster speeds (≥2 miles per hour) is associated with lower hypertension risk in postmenopausal women. Walking should be encouraged as part of hypertension prevention in older adults.

Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women's Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.

Objective Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative. Methods Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a). Results The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations. Conclusions We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.

Introduction: The association of egg or dietary cholesterol intake with risk of cardiovascular disease (CVD) and overall mortality remains a topic of active debate. Hypothesis: Higher egg or dietary cholesterol intake is associated with elevated risk of CVD and all-cause mortality. Methods: We analyzed data from 96,755 women aged 50-79 years who were free of CVD and cancer at baseline (1993-1998)(Women’s Health Initiative). Baseline dietary data were collected using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals of CVD or mortality ascertained through February, 2018. Results: After multivariable adjustment (model 1 in Figure ), higher intakes of egg and dietary cholesterol both were associated with increased risk of CVD (HRs: 1.09 [1.06-1.13] for ½ eggs/day and 1.13 [1.09-1.17] for cholesterol intake of 100 mg/1000 Kcal/day) and all-cause mortality (HRs: 1.10 [1.07-1.12] for egg and 1.16 [1.12-1.19] for cholesterol intake). These associations persisted with further adjustment for other major food groups (e.g. red/processed meat) or nutrients (e.g. saturated fat), or for several potential intermediators (model 2 in Figure ). For both egg and cholesterol intakes, the positive associations with CVD were limited to obese individuals and the associations with all-cause mortality were more pronounced in individuals with diabetes (all P -interaction≤0.002). Among 9451 participants with blood cholesterol measurements, egg or cholesterol intake remained associated with increased CVD and mortality, and the associations were not altered by further adjustment for LDL and HDL cholesterol despite the expected associations of both lipid measures with CVD and mortality ( Figure ). Conclusions: A higher intake of eggs or dietary cholesterol was associated with higher risk of CVD in obese women and overall mortality predominantly in women diagnosed with diabetes. These associations appeared not attributable to blood cholesterol.

Background Coffee and tea are two of the most widely consumed beverages worldwide and have been associated with reduced risk of mortality in some studies. However, it is unknown whether consumption of these beverages is associated with survival to an advanced age. Objective To examine associations of coffee and tea consumption with survival to age 90 years. Design Prospective cohort study among participants from the Women's Health Initiative, recruited during 1993 to 1998 and followed up until March 31, 2018. Setting The setting included 40 US clinical centers. Participants A racially and ethnically diverse cohort of 27,480 older women, aged 65 to 81 years at baseline. Measurements Women were classified as having either survived to age 90 years or died before this age. Consumption of caffeinated and decaffeinated coffee and caffeinated tea was assessed at baseline and categorized as 0, 1, 2 to 3, or 4 or more cups/day. Associations of coffee and tea consumption with survival to age 90 years were examined using logistic regression models adjusted for sociodemographic characteristics, lifestyle behaviors, dietary quality, and chronic disease history. Results A total of 14,659 (53.3%) women survived to age 90 years during follow-up. Caffeinated coffee, decaffeinated coffee, or caffeinated tea consumption was not significantly associated with survival to age 90 years after adjusting for confounders. Findings did not significantly vary by smoking, body mass index, or race/ethnicity. Conclusion No amount of coffee or tea consumption was associated with late-age survival among older women. These findings may be reassuring to older women who consume coffee and tea as part of their daily diets but do not support drinking these beverages to achieve longevity.

Left ventricular mass (LVM) has been shown to serve as a measure of target organ damage resulting from chronic exposure to several risk factors. Data on the association of midlife LVM with later cognitive performance are sparse. We studied 721 adults (mean age 56 years at baseline) enrolled in the Strong Heart Study (SHS, 1993–1995) and the ancillary CDCAI (Cerebrovascular Disease and Its Consequences in American Indians) Study (2010–2013), a study population with high prevalence of cardiovascular disease. LVM was assessed with transthoracic echocardiography at baseline in 1993 to 1995. Cranial magnetic resonance imaging and cognitive testing were undertaken between 2010 and 2013. Generalized estimating equations were used to model associations between LVM and later imaging and cognition outcomes. The mean follow-up period was 17 years. A difference of 25 g in higher LVM was associated with marginally lower hippocampal volume (0.01%; 95% confidence interval, 0.02–0.00; P =0.001) and higher white matter grade (0.10; 95% confidence interval, 0.02–0.18; P =0.014). Functionally, participants with higher LVM tended to have slightly lower scores on the modified mini-mental state examination (0.58; 95% confidence interval, 1.08–0.08; P =0.024). The main results persisted after adjusting for blood pressure levels or vascular disease. The small overall effect sizes are partly explained by survival bias because of the high prevalence of cardiovascular disease in our population. Our findings emphasize the role of cardiovascular health in midlife as a target for the prevention of deleterious cognitive and functional outcomes in later life.

The aim of this study was to investigate whether red meat consumption is related to changes in left ventricular mass (LVM), left atrial diameter and carotid atherosclerosis in American Indians.We prospectively analyzed echocardiographic and carotid ultrasound data of 1090 adults aged 40 years and older enrolled in the Strong Heart Family Study who were free of cardiovascular disease at baseline - 535 (49%) were hypertensive and 555 (51%) participants were nonhypertensive. Processed and unprocessed red meat intake was ascertained by using a Block food-frequency questionnaire at baseline. Cardiac and vascular biomarkers were assessed at baseline and 4 years later. Marginal models with multivariate adjustment were used to assess the associations of red meat intake with LVM, left atrial diameter, intima-media thickness and presence and extent of carotid atherosclerosis.Participants with hypertension were older, had a higher BMI, were more likely to be diabetic and less physically active. Processed and unprocessed red meat consumption was related to an increase in the presence of atherosclerotic plaques in male and female hypertensive individuals. In male hypertensive participants, processed meat intake was further observed to be associated with an increase in intima-media thickness, atrial diameter but not LVM. In nonhypertensive participants, neither unprocessed nor processed red meat intake was associated with changes in cardiac parameters or carotid atherosclerosis.Over a 4-year period, red meat consumption was related to cardiovascular target organ damage in hypertensive American Indians. These findings emphasize the importance of dietary measures for cardiovascular disease prevention.

Objective Dietary protein restriction is recommended for patients with moderate to severe renal insufficiency. Long-term data on the relationship between dietary protein sources and risk for incident kidney disease in individuals with normal kidney function are largely missing. This study aimed to assess the association between dietary protein sources and incident chronic kidney disease (CKD). Design Prospective cohort. Setting Atherosclerosis Risk in Communities study participants from 4 US communities. Subjects A total of 11,952 adults aged 44-66 years in 1987-1989 who were free of diabetes mellitus, cardiovascular disease, and had an estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m 2 . Main Outcome Measure A 66-item food frequency questionnaire was used to assess food intake. CKD stage 3 was defined as a decrease in eGFR of ≥25% from baseline resulting in an eGFR of less than 60 mL/minute/1.73 m 2 ; CKD-related hospitalization; CKD-related death; or end-stage renal disease. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results During a median follow-up of 23 years, there were 2,632 incident CKD cases. Red and processed meat consumption was associated with increased CKD risk (HR Q5 vs. Q1 : 1.23, 95% CI: 1.06-1.42, p trend = 0.01). In contrast, higher dietary intake of nuts, legumes, and low-fat dairy products was associated with lower CKD risk (nuts: HR Q5 vs. Q1 : 0.81, 95% CI: 0.72-0.92, p trend Q5 vs. Q1 : 0.75, 95% CI: 0.65-0.85, p trend Q5 vs. Q1 : 0.83, 95% CI: 0.72-0.95, p trend = 0.03). Conclusion There were varied associations of specific dietary protein sources with risk of incident CKD; with red and processed meat being adversely associated with CKD risk; and nuts, low-fat dairy products, and legumes being protective against the development of CKD.

We examined associations of diet, physical activity, cigarette smoking, and body mass index (BMI), separately and as a cumulative lifestyle score, with incident hospitalized HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). This analysis included 40,095 postmenopausal women in the Women's Health Initiative clinical trial and observational studies, aged 50-79 years and without self-reported HF at baseline. A healthy lifestyle score (HLS) was developed, in which women received 1 point for each healthy lifestyle. A weighted HLS was also created to examine the independent magnitude of each of the lifestyle factors in HF subtypes. Trained adjudicators determined cases of incident hospitalized HF, HFpEF, HFrEF through March 2018. Multiple variable Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up period of 14.5 years, 659 incident HFrEF and 1276 HFpEF cases were documented. Across unweighted HLS of 0 (referent), 1, 2, 3, and 4, multivariable adjusted HRs (95% CI) for HFrEF were 1.00, 0.52 (0.38, 0.71), 0.40 (0.29, 0.56), 0.33 (0.23, 0.48), and 0.33 (0.19, 0.56) (P-trend = 0.03) and for HFpEF were 1.00, 0.47 (0.37, 0.59), 0.39 (0.30, 0.49), 0.26 (0.20, 0.34), and 0.23 (0.15, 0.35) (P-trend 0.001). Results were similar for the weighted HLS. Our findings suggest that following a healthy lifestyle pattern is associated with lower risks of HFpEF and HFrEF among postmenopausal women.

Acute chest pain is one of the most important cardinal symptoms in medicine. There are several important differential diagnoses for chest pain. Therefore, a thorough history and physical examination, as well as the 12-lead ECG and laboratory tests are crucial. In clinical practice, it is useful to distinguish between cardiac chest pain and other forms of chest pain in order to treat patients appropriately and to exclude potentially life-threatening conditions.

A 75-year-old woman was admitted to our institution for acute abdominal pain. She had a history of atrial fibrillation, pacemaker implantation and diastolic heart failure. At time of admission, she was under oral anticoagulation therapy with apixaban.The X-ray of the chest showed a reduction in transparency surrounding the calcification of the aortic arch. CT angiography revealed evidence of an intramural hematoma of the aorta ranging from the left subclavian artery to the inferior mesenteric artery with presence of localized ulcer-like projections.Since the IMH was limited to the descending aorta, we first chose a conservative strategy with tight blood pressure control. Unfortunately, the patients' clinical symptoms did not improve. Her pain persisted despite medical treatment. After joint discussion with surgery and radiology, an endovascular aortic repair was successfully performed. The patient recovered well and could be discharged from the hospital.Acute aortic syndrome describes a life-threatening condition, including acute aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. Rapid and correct diagnosis is imperative for adequate management. Once the definitive diagnosis of an aortic syndrome is made, prompt and appropriate therapeutic interventions should be undertaken. Urgent surgery for acute aortic syndromes involving the ascending aorta (Stanford Type A) and medical therapy alone for uncomplicated cases involving the descending aorta (Stanford Type B) are typically recommended. In complicated Stanford Type B situations, endovascular aortic repair (TEVAR) should be considered.Eine 75-jährige Patientin wurde wegen akuter Übelkeit, Völlegefühl, Erbrechen ohne Blutbeimengung und unspezifischer abdomineller Schmerzsymptomatik nächtlich aufgenommen. In der Anamnese fand sich neben einem Vorhofflimmern, weswegen sie vollantikoaguliert war, ein Z. n. Schrittmacheranlage sowie eine diastolische Herzinsuffizienz.Im Röntgenbild des Thorax fiel eine die Kalkspange des Aortenbogens umgebende Transparenzminderung auf. Eine CT-Angiografie erbrachte den Nachweis eines intramuralen Hämatoms (IMH) der Aorta vom Abgang der A. subclavia links bis nach abdominell zum Abgang der A. mesenterica inferior mit fokalen Ulzerationen.Da sich das IMH auf die Aorta descendens beschränkte, wurde zunächst ein konservatives Vorgehen mit blutdrucksenkenden Maßnahmen gewählt. Die Beschwerdesymptomatik der Patientin verbesserte sich trotz medikamentöser Therapie nicht. Aufgrund des komplizierten Verlaufs wurde nach interdisziplinärer Fallbesprechung eine transfemorale endovaskuläre Reparatur der Aorta mittels Stentgraft-Prothese durchgeführt. Postinterventionell erholte sich die Patientin gut von dem Eingriff, war beschwerdefrei und konnte entlassen werden.Entscheidend für das Management eines IMH ist eine zeitnahe Diagnose und die korrekte Klassifizierung der Ausdehnung (Typ Stanford A oder Stanford B). Während für ein IMH Typ Stanford A die Indikation zur chirurgischen Versorgung gegeben ist, ist bei Typ Stanford B eine interdisziplinäre Falldiskussion sinnvoll. Bei Vorliegen eines unkomplizierten IMH ist ein konservatives Prozedere mit adäquater Einstellung einer arteriellen Hypertonie empfohlen. Bei komplizierten Verläufen sollte die endovaskuläre Therapie (Thoracic Endovascular Repair/TEVAR) als Versorgungsmöglichkeit erwogen werden.