Cardiovascular Medication Use Research Articles

Twenty-year trends in peripheral artery disease, lower extremity revascularization, and lower extremity amputation in newly diagnosed type 2 diabetes

Abstract Background Trends in risk of lower extremity complications in patients with newly diagnosed type 2 diabetes (T2DM) are largely unexplored. Purpose To examine the 5-year risk trends of peripheral artery disease (PAD), lower extremity revascularization (LER), and lower extremity amputation (LEA) in patients with newly diagnosed T2DM over a 25-year study period. Methods We conducted a cohort study that included all patients in Denmark diagnosed with T2DM from 1996 to 2015, who had no prior hospital diagnosis of atherosclerotic cardiovascular disease. These patients were age- and sex-matched with up to three comparisons from the general population. Individuals were assigned to 5-year calendar periods based on their year of inclusion and were followed for 5 years. The primary outcomes were the 5-year risks of PAD, LER, and LEA. Age- and sex-adjusted hazard ratios (aHR) were computed using Cox regression analysis. Results The study cohort consisted of 288,825 newly diagnosed T2DM patients (52% males; median age 61 years) and 782,232 comparisons from the general population. From 1996-2000 to 2015-2020, the 5-year risk of PAD decreased from 2.2% to 1.2% (aHR 0.56 [95% CI 0.52-0.61]), LER from 0.7% to 0.5% (aHR 0.73 [95% CI 0.63-0.84]), and LEA from 1.0% to 0.4% (aHR 0.44 [95% CI 0.38-0.50]) in T2DM patients (Figure). Compared with the general population, the 5-year risk differences decreased from 1.4% to 0.5% for PAD, from 0.4% to 0.2% for LER, and from 0.8% to 0.3% for LEA. The distribution of LEA types (hip/thigh, knee/lower leg, or ankle/foot/toe amputation) remained largely stable over time in T2DM patients. Use of prophylactic cardiovascular medications in T2DM patients increased notably during the study period, especially use of statins (5% to 50%) and multiple antihypertensive drugs (18% to 33%). Conclusions Over recent decades, the risks of PAD, LER, and LEA have decreased in patients with newly diagnosed T2DM, approaching the risk levels observed in the general population. This coincided with a great increase in use of prophylactic cardiovascular medications among T2DM patients.Trends in lower extremity complications.

Long-term outcomes in women with a history of peripartum cardiomyopathy

Abstract Background Peripartum cardiomyopathy (PPCM) remains an important cause of cardiac-related maternal morbidity and mortality in previously healthy young women. Data on the long-term clinical course of PPCM are sparse. In this study, we report the long-term outcomes in patients with PPCM. Methods and Results Long-term follow-up (median 9.6, min 5, and max 24 years) was available in 72 women with PPCM followed in a cardio-obstetrics clinic. Five-year follow-up data were available for 19 PPCM patients, 10-year follow-up data for 24 PPCM patients, and more than 15 years of follow-up data for 24 PPCM patients. Seven patients were lost to cardiac follow-up but are known to be alive. The mean age at diagnosis was 35 ± 7 years, and 85% were Caucasian. The mean parity was 2.2 ± 1.3, and gravidity was 2.7 ± 1.7. Twin pregnancies were reported in 13% of cases. Pre-eclampsia was present in 25% of the patients and the development of hypertension in the long-term was documented in 18%. The mean LVEF was 34.5 ± 9.9% at diagnosis. One-year LVEF data were available in 72 patients: 54 patients (75%) experienced LV recovery (LVEF≥ 50%). After 1 year, the mean LVEF was 53.4± 8.2%. Among patients remained with LV<50% at one year (n=10) no LV function recovery was reported at long-term follow-up. At a median follow-up of 9.6 years (n=66) mean LVEF was 52.1±10.4%, nine patients had a reduction in LVEF (<50%) function in the long-term follow-up with a mean LVEF of 46.1± 2.1%. Out of 72 PPCM patients, 3 patients developed arrhythmia, in one woman coronary artery disease occurred and 7 underwent pacemaker implantation. Almost half of patients (n=65) remained with long term treatment of b-blockers, 38% received medications for hypertension or heart failure. No cases of myocardial infarctions, cardiovascular death, or heart transplantations were reported. Two women died during follow-up: one with normal LVEF died from breast cancer, and another patient with reduced LVEF and severe diabetes. The cause of her death remained unclear. During follow-up, 30 women had ≥ 1 subsequent pregnancy (SSP), and there was no reduction in their mean LVEF before SSP 57.0 ± 5.4% and at long-term follow-up was 59.6± 1.3% (p=ns). Conclusion Our study demonstrates favorable long-term outcomes with high and stable recovery rates with low mortality rates, and no impact of subsequent pregnancies on the clinical course of the condition. Nevertheless, persisting or new diagnosis of hypertension and use of cardiovascular medications were noted in the long term follow up.

Effect of salt substitute and antihypertensive medications among high cardiovascular risk patients: A sub-study of Salt Substitute and Stroke Study (SSaSS).

The relationship between the differential protective effect of salt substitute between hypertensive and normotensive individuals and the use of cardiovascular medications remains unclear. This study involved 4211 individuals with a history of stroke or hypertension who participated in the Salt Substitute and Stroke Study (SSaSS) from 120 villages in Shanxi Province. The aim of this study was to investigate the differences in major adverse cardiovascular events and blood pressure changes between the salt substitute and the regular salt group in the subgroups of participants taking different antihypertensive medications. Mixed models were employed and adjusted for the cluster effect (village) and potential confounding variables. During the average follow-up period of 4.66 years, a significantly protective effect of salt substitute on reducing the risk of cardiovascular events was observed in the participants who taking antihypertensive medications (rate ratio: 0.81, 95% CI: 0.68 to 0.95. p=0.011), whereas no significant effect in participants not taking antihypertensive medications (rate ratio: 0.91, 95% CI: 0.62 to 1.32, p=0.612). Significant effects to lower systolic blood pressure of the salt substitutes were observed in the participants who took different antihypertensive medications. This study emphasized that the use of salt substitutes might enhance the efficacy of anti-hypertensive medications in lowering blood pressure and reducing the risk of adverse cardiovascular events.

Pre-Existing Atrial Fibrillation in Hospitalized Patients with COVID-19: Insights from the CARDIO COVID 19-20 Registry.

Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.

Effect modification by statin use status on the association between fine particulate matter (PM2.5) and cardiovascular mortality.

Numerous studies have linked fine particulate matter (PM2.5) to increased cardiovascular mortality. Less is known how the PM2.5-cardiovascular mortality association varies by use of cardiovascular medications. This study sought to quantify effect modification by statin use status on the associations between long-term exposure to PM2.5 and mortality from any cardiovascular cause, coronary heart disease (CHD), and stroke. In this nested case-control study, we followed 1.2 million community-dwelling adults aged ≥66 years who lived in Ontario, Canada from 2000 through 2018. Cases were patients who died from the three causes. Each case was individually matched to up to 30 randomly selected controls using incidence density sampling. Conditional logistic regression models were used to estimate odds ratios (ORs) for the associations between PM2.5 and mortality. We evaluated the presence of effect modification considering both multiplicative (ratio of ORs) and additive scales (the relative excess risk due to interaction, RERI). Exposure to PM2.5 increased the risks for cardiovascular, CHD, and stroke mortality. For all three causes of death, compared with statin users, stronger PM2.5-mortality associations were observed among non-users [e.g. for cardiovascular mortality corresponding to each interquartile range increase in PM2.5, OR = 1.042 (95% CI, 1.032-1.053) vs OR = 1.009 (95% CI, 0.996-1.022) in users, ratio of ORs = 1.033 (95% CI, 1.019-1.047), RERI = 0.039 (95% CI, 0.025-0.050)]. Among users, partially adherent users exhibited a higher risk of PM2.5-associated mortality than fully adherent users. The associations of chronic exposure to PM2.5 with cardiovascular and CHD mortality were stronger among statin non-users compared to users.

Heart rate from intermittent home measurements within an atrial fibrillation screening program is associated with mortality

Abstract Introduction A high resting heart rate is a predictor of cardiovascular disease and cardiovascular mortality. Studies on the association between heart rate and outcomes often measure heart rate at a single time point, even though multiple measurements may be a stronger predictor of cardiovascular risk. Indeed, the association between short-term home heart rate measurements and outcomes has not been extensively studied. Purpose This sub study of the STROKESTOP trial explores the association of baseline and home resting heart rate measurements with all-cause and cardiovascular mortality. Methods The STROKESTOP randomised controlled trial consisted of an atrial fibrillation (AF) screening program among the 75- and 76-year-old inhabitants of two Swedish regions. Participants in the intervention group were invited to a two week intermittent screening program, consisting of twice daily measurements with an ECG-based handheld device. For this sub analysis, baseline heart rate, the median of 5 home morning heart rates and the median of 5 home evening heart rates were evaluated. Associations were evaluated by heart rate quintiles (41-63 bpm, 64-70 bpm, 71-76 bpm, 77-84 bpm and ≥85 bpm), with 64-70 bpm as the reference category. Hazard rations were obtained by Cox regression analysis. The full multivariable model included demograhic factors such as sex and educational level, medical history of several diseases and the use of cardiovascular medication. Both all-cause mortality and cardiovascular mortality were evaluated. Results In total, 5873 individuals were included in this analysis. Overall, 55.6% were women and the median baseline heart rate was 73 [65-81] bpm, whereas the median of morning heart rates was 71 [64-78] bpm and that of evening heart rates 71 [65-79] bpm. Having a baseline heart rate in the highest quintile compared to the reference quintile, showed a hazard ratio (HR) for all-cause mortality in unadjusted analysis of 1.39 (1.11-1.73) (p=0.004), and of 1.51 (1.20-1.90) in the fully adjusted analysis (p<.001). For cardiovascular mortality, HRs were 1.78 (1.21-2.63) (p=0.004) and 2.13 (1.42-3.20) (p=<.001), respectively. The association between the highest heart rate and all-cause mortality and cardiovascular mortality were substantially strengthened when median morning heart rates were considered (HR 2.03 (1.61-2.56) and 2.18 (1.72-2.76), p<.001 for all-cause mortality on univariable and multivariable analysis, HR 2.35 (1.57-3.51) and 2.59 (1.72-3.92), p<.001) for cardiovascular mortality). Associations between home evening heart rates and all-cause and cardiovascular mortality were not substantially stronger compared to the associations with baseline heart rate. Conclusion Our study shows that home-measured morning heart rate is more strongly associated with all-cause and cardiovascular mortality compared to a single time-point office heart rate.Hazard ratios for mortality

Effects on physical activity, physical fitness and well-being in a 36-months randomized controlled study, comparing a multimodal hospital-based intervention programme for primary cardiovascular prevention with usual care

BackgroundCardiovascular disease is a major cause of mortality and morbidity worldwide, and primary prevention efforts are poorly developed in people at high cardiovascular risk. On this background, we performed the Hjerteløftet Study and demonstrated that participation over 36 months in a multimodal primary prevention programme, significantly reduced validated cardiovascular risk scores. In the current substudy we aimed to further explore several elements and effects following the intervention programme.MethodsA random sample from the original Hjerteløftet Study was included for further examinations (n = 255, 40% women), and these patients were already randomized to an intervention group (IG) (n = 127), or a control group (CG) (n = 128). We compared changes from baseline to 36-months follow-up in physical activity, cardiorespiratory fitness, psychological well-being (WHO-5), cardiovascular medication use, smoking habits, and cardiometabolic risk factors (blood pressure, lipids, blood glucose, HbA1c, Apolipoprotein A-I, Apolipoprotein B and high-sensitive C-reactive protein).ResultsSelf-reported physical activity increased significantly with absolute difference in mean delta Physical Activity Index score in the IG compared to the CG: 0.90, 95% CI: 0.10 to 1.70, p = 0.028 (ANCOVA). There were no corresponding differences in cardiorespiratory fitness. The participation resulted in psychological well-being improvement in both groups with a larger increase in the IG compared to the CG. The mean difference in delta WHO-5 score was 5.06, 95% CI: 0.68 to 9.45, p = 0.024, and 3.28, 95% CI: -0.69 to 5.25, p = 0.104 when controlled for baseline values (ANCOVA). The use of antihypertensive medication increased significantly more in the CG (p = 0.044). Only minor, nonsignificant changes were observed for traditional risk factors and cardiometabolic variables.ConclusionsParticipation in the Hjerteløftet Study intervention programme resulted in an improved physical activity level, but without changing cardiorespiratory fitness. Participation in the programme also tended to improve psychological well-being, possibly related to increased physical activity, less smoking and less use of cardiovascular medication. Concerning the metabolic status, no major differences were observed, but minor changes may have been concealed by a larger increase in cardiovascular medication use in the control group.Trial registrationClinicalTrials.gov (NCT01741428), 04/12/2012.

The Effect of Cardiovascular Medication on Heart Rate Variability in Patients Presenting with Early Sepsis at the Emergency Department: A Prospective Cohort Study

Our SepsiVit study showed that long-term, automatically analyzed ECG recordings can be used to determine heart rate variability (HRV) features associated with the clinical deterioration of early septic patients at the ED. This study focus on the influence of cardiovascular medication on HRV in patients with early sepsis at the ED. This study is an exploratory post-hoc analysis of our SepsiVit study. Eligible patients were connected to a mobile bedside monitor for continuously ECG measurements. The first 3 hours were analyzed for this study. Between January 2017 and December 2018, 171 patients were included with early sepsis, defined as infection and two or more systemic inflammatory response syndrome criteria. We excluded sixteen patients because of insufficient measurements. Therefore, we included 155 patients in the final analysis: 72.9% with sepsis, 2.6% with septic shock, and 24.5% classified as infection. In 9.0% of the patients, medication directly impacting cardiac contractility was administered, while 22.6% received medication with an indirect effect. A combination of both types of medication was prescribed to 17.4% of the patients. The majority of patients (51.0%) did not utilize any cardiovascular medication. Patients using both medication with direct and indirect effect were on average 10 years older than patients using no cardiovascular medication (p 0.037). No differences in vital signs or HRV parameters were found in patients using cardiovascular medication. Our results showed that HRV is not influenced by cardiovascular medication. Consequently, the correction of HRV features for the use of cardiovascular medication is unnecessary when analyzing, modelling, and interpreting these signals.

Drug therapy for arterial hypertension and atrial fibrillation in frail patients : Are there any new insights and recommendations?

The frail and elderly are considered to be at particular risk of suffering an adverse drug reaction. Empirical studies confirm the increased rate of adverse drug reactions. Whether frailty perse impairs drug metabolism or the underlying organ ageing processes and multimorbidity cannot be answered with certainty based on current data. Cardiovascular diseases exhibit aconsiderable interdependence with frailty. For example, there is adisproportionate syndromal interdependence between heart failure and frailty, and the typical ageing processes of the sinus node can be interpreted as heartbeat frailty. Multimorbidity in the elderly often includes acluster of chronic cardiovascular diseases, often leading to the use of several cardiovascular medications as required. More recent definitions of polypharmacy assess the appropriateness of drugs rather than their number. The Fit-fOR-The-Aged (FORTA) list, the PRISCUS 2.0 list and the "Cochrane Library Special Collection on deprescribing", for example, offer apractice-oriented assessment aid. In the treatment of arterial hypertension, the target values for older people have also been set ever lower in recent years. In the case of frail elderly people, on the other hand, the guidelines do not specify astrict blood pressure target corridor; tolerability is the crucial factor here. When initiating antihypertensive therapy in frail individuals, one can consider monotherapy-in adeparture from the standard case of dual combination therapy. The OPTIMISE study showed that discontinuation of one blood pressure medication did not lead to better tolerability of the drug therapy. Current studies come to differing conclusions regarding the risk-benefit assessment of new oral anticoagulants compared to vitaminK antagonists in the anticoagulation of frail elderly people with atrial fibrillation. Shared decision-making, which could improve adherence particularly in older people, is recommended.

The evaluation of clinical factors affecting oral health impacts on the quality of life of Iranian elderly patients visiting dental clinics: A cross-sectional study.

Iran will soon have an aging population. Healthcare providers must consider factors affecting the quality of life for those 60 and older. Understanding oral health as one of these factors can improve the elderly's quality of life. Oral health-related quality of life (OHRQoL) is a crucial reflection of individuals' general well-being and their overall quality of life linked to health. This study aimed to evaluate the OHRQoL among elderly Iranians referring to Azad University of Medical Sciences in Tehran. In this cross-sectional study, 171 individuals over 65 (93 men and 78 women) were evaluated using OHIP-14 and GOHAI-12 questionnaires to analyze their quality of life. Gender, age, systemic diseases, using medications and dentures, the number of remaining teeth, and oral lesions were recorded. Salivary flow and xerostomia were analyzed with the spitting method and xerostomia index questionnaire, respectively. Also, four main flavor solutions were used to evaluate the taste perception. Data were analyzed using PASS11 and p value<.05 was the significance level. Based on OHIP-14 and GOHAI-12, Iranian older people's quality of life can be affected by cardiovascular diseases, hypertension, xerostomia, and the number of remaining teeth (p<.05). The results also showed a significant correlation between the OHIP-14 and GOHAI-12 scores (p<.001). Both indexes revealed that the number of remaining teeth, xerostomia, salivary flow, and taste perception greatly influenced participants' quality of life. More remaining teeth, improved salivary flow, and better perception of sweetness and sourness were all linked to a higher quality of life, while increased xerostomia, reduced salivary flow, and bitter taste perception were linked to a decline in overall well-being. Cardiovascular diseases, hypertension, and medication use were also found to significantly impact quality of life. This study's results indicate that cardiovascular diseases, hypertension, dry mouth, and tooth loss can negatively impact the elderly's quality of life. So, improving both systemic and oral health is vital for enhancing life quality in this age group.

Risk Factors for Immune Checkpoint Inhibitor-Related Myocarditis: An Integrative Review.

The purpose of this integrative literature review was to determine factors that increase the risk of immune checkpoint inhibitor (ICI)-related myocarditis in the cancer patient population. A literature review was conducted using the following databases: PubMed, Scopus, and Cochrane Review. Dates searched were from inception through March 1, 2022. Inclusion criteria included English language, cancer patients receiving ICI treatment, and risk factors for myocarditis. Articles were excluded if they were a non-human study, duplicate, had an irrelevant title or content, or were a review or commentary. Patients with cancer who receive ICIs have an associated increased risk of myocarditis if they are older than 64 years, have a body mass index (BMI) greater than 28, and have a history of cardiovascular medication use. Myocarditis remains a rare cardiovascular adverse effect of ICIs. However, the mortality risk among this subset of patients remains high. Additional prospective randomized-controlled trials would be beneficial to further determine a causal relationship between risk factors for ICI-related myocarditis. Risk stratification tools may allow oncology medical providers to identify patients at a higher risk of ICI-related myocarditis to increase earlier surveillance.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

Risk Factors for Medial and Intimal Intracranial Internal Carotid Artery Calcification in Men and Women with Cardiovascular Disease: The UCC-SMART Study

Introduction: Calcifications of the intracranial internal carotid artery (iICA) can lead to an increased risk for stroke. Two types of iICA calcification are known: those affecting the tunica intima or the tunica media. In extracranial arteries, risk factors and calcification patterns are different in women and men, but little is known regarding the iICA. In this study, we aimed to identify sex-specific risk profiles and medications associated to intimal and medial iICA calcification in patients with cardiovascular disease (CVD). Methods: Participants of the UCC-SMART cohort undergoing a non-contrast head CT within 6 months from the study inclusion were considered (n = 475). Intimal or medial iICA calcification pattern was assessed using a previously histology-validated method. Sex-stratified associations between calcification pattern and cardiovascular risk factors, laboratory parameters, and medication use were calculated using Poisson regression analysis with robust standard errors. Results: Two hundred and four women and 271 men (age range 24–79 years) were included. 45.4% of men and 34.8% of women showed intimal iICA calcification, while 28.4% of men and 24.0% of women showed medial iICA calcification. Minimal or no iICA calcification was observed in 26.2% of men and in 41.2% of women (reference group). Older age was associated with both calcification patterns in women and men. In women, use of vitamin K antagonists and lipid-lowering drugs was associated to medial calcification, while systolic blood pressure and glucose levels were associated to intimal calcification. In men, current smoking was associated to intimal calcification. Conclusions: Women and men with CVD show differences in risk profiles and medication use associated to intimal and medial iCA calcification.

Prescription patterns of antidiabetic and cardiovascular preventive medications in community-dwelling older adults with type 2 diabetes mellitus: a cross-sectional study.

To describe trends in antidiabetics drug prescription patterns in community-dwelling older adults with type 2 diabetes mellitus (T2DM) and to evaluate the use of cardiovascular preventive medications among those diagnosed with atherosclerotic cardiovascular disease (ASCVD). This cross-sectional, face-to-face interview study that comprised community-dwelling older adults (≥ 65 years) diagnosed with T2DM. The study questionnaire included the patients' demographics, clinical data, and current medication use. Patients with established ASCVD were further classified into low (i.e., not receiving evidence-based therapy or only one) and high (i.e., receiving at least two evidence-based therapies) composite score groups. Bivariate analysis followed by multivariable logistic regression analysis were performed to evaluate the demographic/clinical characteristics associated with the use of antidiabetic monotherapy/polytherapy and evidence-based pharmacotherapy. A total of 500 older adults were enrolled. The mean age of included participants was 73 ± 7 years, 310 participants (62%) were males, and 385 participants (77.0%) had established ASCVD. Antidiabetic monotherapy was reported in 251 participants (50.2%), with metformin followed by sulfonylureas being the most commonly prescribed drugs as monotherapy. The results of the multivariable analysis showed that age [odds ratio (OR) = 0.89, 95% CI: 0.85-0.94, P < 0.001], obesity (OR = 4.18, 95% CI: 1.63-10.36, P = 0.003), hypertension (OR = 4.2, 95% CI: 1.22-7.66, P = 0.04), and dyslipidemia (OR = 4.1, 95% CI: 1.28-8.30, P = 0.01), were significantly associated with the prescription of cardiovascular preventive medications. Only one in twenty-one participant with T2DM and ASCVD collectively received three guideline-recommended therapies, indicating a deficiency of utilization of cardiovascular preventive drugs.

Atherosclerotic Cardiovascular Disease Risk and Longitudinal Risk Factor Management Among Patients With Breast Cancer

BackgroundCardiovascular disease is the leading cause of noncancer mortality for breast cancer survivors. Data are limited regarding patient-level atherosclerotic cardiovascular disease (ASCVD) risk estimation and preventive medication use. This study aimed to characterize ASCVD risk and longitudinal preventive medication use for a cohort of patients with nonmetastatic breast cancer. Patients and MethodsThis retrospective cohort study included 326 patients at an academic medical center in Boston, Massachusetts diagnosed with nonmetastatic breast cancer or ductal carcinoma in situ from January 2009 through December 2015. Patient demographics, clinical characteristics, laboratory studies, medication exposure, and incident cardiovascular outcomes were collected. Estimated 10-year ASCVD risk was calculated for all patients from nonlaboratory clinical parameters. ResultsMedian follow up time was 6.5 years (IQR 5.0, 8.1). At cancer diagnosis, 23 patients (7.1%) had established ASCVD. Among those without ASCVD, 10-year estimated ASCVD risk was ≥20% for 77 patients (25.4%) and 7.5% to <20% for 114 patients (37.6%). Two-hundred and sixteen patients (66.3%) had an indication for lipid-lowering therapy at cancer diagnosis, 123 of whom (57.0%) received a statin during the study. Among 100 patients with ASCVD or estimated 10-year ASCVD risk ≥20%, 92 (92.0%) received an antihypertensive medication during the study. Clinic blood pressure >140/90 mmHg was observed in 33.0% to 55.6% of these patients at each follow up assessment. ConclusionA majority of patients in this breast cancer cohort had an elevated risk of ASCVD at the time of cancer diagnosis. Modifiable ASCVD risk factors were frequently untreated or uncontrolled in the years following cancer treatment.

Losartan Has a Comparable Effect to Human Recombinant ACE2 in Reducing Interleukin-6 (IL-6) Levels on Human Adipocytes Exposed to SARS-CoV-2 Spike Protein

BACKGROUND: High angiotensin-converting enzyme 2 (ACE2) expression in adipocyte cells facilitates the initiation of SARS-CoV-2 infection and triggers a cytokine storm. This finding suggests that obesity is an independent risk factor for the severity of the symptoms caused by COVID-19. The use of cardiovascular medications that focus on ACE2, such as angiotensin II receptor blockers, remains controversial, and their effects on inflammatory cytokine production and ACE2 expression in cells, especially adipocytes, remain inconsistent.METHODS: The human adipocytes were isolated from obese donor subcutaneous adipose tissue and infected with the subunit S1 spike protein from SARS-Cov-2. The adipocytes were later treated with either hrsACE2 or losartan. The levels of ACE2 and inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured using enzyme linked immunosorbent assay (ELISA). ACE2 and S1 spike protein binding assays were also performed. RESULTS: ACE2, IL-6, and TNF-α levels were significantly increased in human adipocyte cells infected with SARS-Cov-2 but not IL-1β. There was a statistically significant positive correlation between ACE2 and IL-6 (r=0.878, p&lt;0.001). Administration of losartan and hrsACE2 was shown to reduce ACE2 levels and its binding to the SARS-CoV-2 S1 spike protein, and IL-6 levels were statistically significant, but had no significant effect on IL-1β or TNF-α levels.CONCLUSION: This study shows that the administration of losartan in COVID-19 may not be harmful, but instead has a protective effect similar to that of hrsACE2 in preventing a cytokine storm, especially IL-6.KEYWORDS: obesity, SARS-CoV-2, losartan, IL-6, ACE2

The Association between Birthweight and Use of Cardiovascular Medications: The Role of Health Behaviors.

There is limited evidence on the effect of low birthweight on the use of cardiovascular medications and the role of health behaviors. This study aims to determine the independent effect of low birthweight and its combination with adult health behaviors on the number of dispensed cardiovascular medications. We included 15618 participants with information on birthweight and self-reported health behaviors. Dispensed cardiovascular medications were identified from the Prescribed Drug Register based on a three-digit level Anatomical Therapeutic Chemical classification code (C01 to C10 and B01) and categorized into 0, 1, and ≥2 different types of medications. We applied multinomial logistic regression models estimating odds ratios (ORs) and 95% confidence intervals (CIs). Participants with low birthweight had a higher estimated OR of using ≥2 types of cardiovascular medications (OR = 1.46, 95% CI = 1.06, 2.01). Further, an increased risk for using ≥2 types of cardiovascular medications was found in participants with poor health behaviors for normal (OR = 2.17, 95% CI = 1.80, 2.62) and high (OR = 1.84, 95% CI = 1.29, 2.62) birthweight. The strongest effect on using ≥2 types of cardiovascular medications was found for low birthweight and poor health behaviors (OR = 3.14, 95% CI = 1.80, 5.50). This cohort study provides evidence that low birthweight increases the risk of using more types of cardiovascular medications in adulthood. This study also suggests that ideal health behaviors reduce this risk.

SAT285 Biomarkers For Cardiovascular Disease And Inflammation Are Altered In Autoimmune Addison's Disease

Abstract Disclosure: Å.B. Sævik: None. G. Ueland: None. A. Åkerman: None. P. Methlie: None. M. Quinkler: None. A. Jørgensen: None. C. Höybye: None. A.W. Debowska: None. B. Nedrebø: None. A. Dahle: None. S. Carlsen: None. A.E. Tomkowicz: None. S.T. Sollid: None. I. Nermoen: None. K. Grønning: None. P.M. Dahlqvist: None. G. Grimnes: None. J. Skov: None. T. Finnes: None. S.F. Valland: None. S.E. Holte: None. J. Wahlberg: None. O. Kämpe: None. S. Bensing: None. E.S. Husebye: None. M. Øksnes: None. Background: Population-based studies have shown a wider use of cardiovascular medications in AAD and an increased risk of ischemic heart disease, most pronounced in women. These data suggest that a subgroup of patients may be especially vulnerable, emphasizing the need for clinical tools to evaluate cardiovascular risk at an individual level in AAD. Methods: We first mapped 177 cardiovascular and inflammatory biomarkers in patients with AAD compared with healthy controls overall and stratified for sex (false discovery rate, FDR 5%). Second, we explored biomarker associations to the frequency of adrenal crises and quality of life (P&amp;lt;0.050), and any impact of very high ACTH exposure on biomarker profiles by change in biomarker profiles in patients without residual adrenocortical function (RAF) following injection of ACTH (FDR 5%). Results: Nineteen (11%) biomarkers significantly differed between patients with AAD and controls after correction for multiple testing, of which all but one (ST1A1) were higher in AAD. The greatest difference in biomarker value was noted for FGF21 (difference 0.80 NPX, P = 0.004). When stratified for sex, seven of the 19 biomarkers were significantly higher in female patients compared to controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9 + PGF), but no significant differences were found between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crisis (r = 0.415, P = 0.006) and AddiQoL-30 scores (r = -0.347, P = 0.028). PD-L2 and leptin significantly declined 60 minutes after injection of ACTH in AAD without RAF (-0.15 NPX, P = 0.0001 and -0.25 NPX, P = 0.0003, respectively). Conclusion: We demonstrate marked differences in cardiovascular and inflammatory biomarker profiles in patients with AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with the frequency of adrenal crises and reduced quality of life. Very high ACTH levels reduce PD-L2 and leptin in a glucocorticoid-independent manner, although the overall effect on biomarker profiles seems small. Presentation: Saturday, June 17, 2023

Utility of standing office blood pressure in detecting hypertension in healthy adults

Current guidelines recommend office blood pressures (BP) be taken in a seated position when screening for hypertension (HTN). Seated BP is known to have limited accuracy in detecting high BP, while the utility of standing BP in diagnosing HTN is unknown. We conducted a cross-sectional study to determine the incremental value of standing BP in diagnosing HTN. Seated, standing, and 24-h ambulatory BPs (ABPM) were obtained in adults without known cardiovascular disease, HTN, or BP medication use. Presence of HTN was defined by the 2017 ACC/AHA and the 2023 ESH HTN guidelines based on ABPM. Area under the receiver-operating-characteristic curve (AUROC) was used to evaluate the diagnostic accuracy of seated and standing BP. Sensitivity and specificity of standing BP was determined using cut-offs derived from Youden’s Index, while sensitivity and specificity of seated BP was determined using the cut-off of 130/80 mmHg and by 140/90 mmHg. Among 125 participants (mean age 49 ± 17 years; 62% female; 24% Black), 33.6% of them had HTN. Sensitivity and specificity of seated systolic BP (SBP) was 43% and 92%, respectively. Cut-offs selected by Youden’s index for standing SBP/diastolic BP (DBP) were 124/81 mmHg according to the 2017 ACC/AHA HTN guidelines, and 123.5/83.5 mmHg according to the 2023 ESH HTN guidelines. Sensitivity and specificity of standing SBP was 71% and 67%, respectively. The AUROC of standing SBP (0.81 [0.71–0.92]) was significantly higher than seated SBP (0.70 [0.49–0.91]), when HTN was defined as average 24-h SBP ≥ 125 mmHg. Moreover, the addition of standing to seated SBP (0.80 [0.68–0.92]) improved HTN detection when compared to seated SBP. These patterns were consistent for both the 2017 ACC/AHA and the 2023 ESH definitions for HTN. In summary, standing BP, alone or in combination with seated BP, outperformed seated BP alone in diagnosing HTN in adults.

Longitudinal association of premature atrial contractions with atrial fibrillation and brain ischemia in people with type 2 diabetes: The Hoorn Diabetes Care System cohort

BackgroundPremature atrial contractions (PACs) are potential markers for imminent onset of both atrial fibrillation (AF) and brain ischemia (BI; transient ischemic attack [TIA] or ischemic stroke). We investigated the association of PACs with incident AF and BI events separately, and of incident AF with BI events in people with type 2 diabetes (T2D) without pre-existing AF or cerebrovascular disease. MethodsA prospective longitudinal study of 12,242 people with T2D without known AF or cerebrovascular disease from the Hoorn Diabetes Care System cohort. Annual measurements (1998–2018) included cardiovascular risk factors, over 85,000 ECGs, and self-reported cardiovascular events. We assessed the association of PACs with incident AF and BI events and of incident AF with BI events using time-dependent Cox-regression models, adjusted for time-varying cardiovascular risk factors and medication use (Hazard Ratios with 95%CIs). ResultsThe baseline mean age was 62.2 ± 11.9 years. During a median follow-up of 7.0 (IQR 3.4–11.0) years, 1031 (8.4 %) participants had PACs, and 566 (4.6 %) had incident AF at any of the median 6 (IQR 3–10) annual ECG recordings. BI events occurred in 517 (4.2 %) people (304 TIAs, 213 ischemic strokes). After adjustment, PACs were associated with incident AF (Hazard Ratio, 1.96 (95%CI, 1.53–2.50)), but not with overall BI events (1.09 (0.76–1.56)), or with TIA (0.91 (0.57–1.46)) or ischemic stroke (1.50 (0.88–2.54)) separately. AF was not associated with BI events (0.95 (0.55–1.63)). ConclusionsIn people with T2D without a history of AF or BI events, PACs are associated with a two-fold increased risk of incident AF.