Pre-existing Cardiovascular Disease Research Articles

Drug therapy of type-2-diabetes-is metformin dispensable now?

Metformin has been recommended as first-line pharmacological therapy in type‑2 diabetes (T2D) since 1998. It was the first medication that demonstrated cardiovascular benefits in obese subjects with T2D. Efficacy and safety of metformin have since been demonstrated in further studies and in real-world data on its use in practice. The recommendation of metformin as baseline therapy has reached wide acceptance internationally. During the period 2015-2021, large cardiovascular safety trials showed superiority for cardiovascular morbidity and partly also mortality outcomes for most substances of the novel antidiabetic substance classes of GLP‑1 receptor agonists and SGLT‑2 inhibitors in people with T2D and very high cardiovascular risk or preexisting cardiovascular disease. The evidence for these two substance classes is now broader than for metformin. Therefore, the question arises as to whether it is still justified to recommend metformin generally as first-line therapy in T2D. This article provides an overview of the study data as well as an overview of the evidence-based guidelines. The status and position of metformin in the treatment of T2D are discussed.

Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management.

Obesity is an epidemic worldwide. Overweight and multiple obesity-related mechanisms, including dysmetabolic alterations, contribute to cardiovascular deleterious effects. Hence, overweight and obesity have been independently associated with increased cardiovascular risk, whose assessment is crucial for preserving life quality and reducing mortality, and to address appropriate therapeutic strategies in obese patients. Beyond the standard of care in managing overweight and obesity in adults (i.e., diet and physical exercise), several relevant pharmacotherapies have been approved, and several procedures and device types for weight loss have been recommended. In such a contest, medical weight management remains one option for treating excess weight. Most drugs used for obesity reduce appetite and increase satiety and, secondarily, slow gastric emptying to reduce body weight and, therefore, act also to improve metabolic parameters. In this contest, agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) modulate different metabolic pathways associated with glucose metabolism, energy homeostasis, antioxidation, and inflammation. Moreover, this class of drugs has shown efficacy in improving glycemic control, reducing the incidence of cardiovascular events in type 2 diabetic patients, and reducing body weight independently of the presence of diabetes. Recently, in overweight or obese patients with pre-existing cardiovascular disease but without diabetes, the GLP-1RA semaglutide reduced the incidence of cardiovascular and cerebrovascular events and death from cardiovascular causes. Thus, semaglutide has been approved for secondary prevention in obese people with cardiovascular disease. Nevertheless, whether this class of drugs is equally effective for primary prevention in obese people has to be demonstrated. In this review, we will summarize updates on the pathophysiology of obesity, the effects of obesity on cardiovascular risk, the impact of different obesity phenotypes on cardiovascular diseases, and the novelties in the clinical management of obesity for cardiovascular prevention.

Metabolic pathways altered by air pollutant exposure in association with coagulation function among the rural elderly

Air pollution exposure has been linked with coagulation function. However, evidence is limited for the relationships between air pollution, coagulation function and metabolomics in humans. We recruited a panel of 130 rural elderly from the Chayashan township in China, all of whom were free of pre-existing cardiovascular diseases and had provided residential address information. We conducted clinical examinations and collected blood samples from these rural elderly for the detection of coagulation biomarkers (e.g, activated partial thromboplastin time, fibrinogen, thrombin time, and prothrombin time) and untargeted metabolites in both December 2021 and August 2022. We used mini ambient air quality monitor to measure the mean levels of five air pollutants (e.g., PM2.5, SO2, NO2, CO and O3) during 1 to 2 weeks before blood sample collection. The Mummichog pathway analysis was used to identified potential metabolic features and pathways. In this study, we identified 5 pathways associated with both air pollution and coagulation function, and further pinpointed eight metabolic features within these pathways. The majority of these features were lipids, including arachidonic acid and linoleic acid. Overall, the findings of this study offer insights into potential mechanisms, particularly lipid metabolism, that may underlie the association between air pollution and coagulation function.

Unfavorable neurological long-term outcome despite eTICI 3 – What are the predictors?

PurposeInterventional stroke therapy has become standard treatment for patients with acute ischemic strokes. Complete reperfusion (eTICI 3) portrays the best possible technical outcome. The purpose of this study was to determine possible predictors for an unfavorable neurological long-term outcome (mRS 3–6) despite achieving the best possible treatment success. MethodsWe evaluated 122 patients with stroke in the anterior circulation and complete reperfusion after mechanical thrombectomy (MT) between May 2010 and March 2020. We performed a binary logistic regression analysis with patient baseline data, stroke severity, comorbidities, premedication and treatment information as independent variables. Results50 of the 122 patients included in our study showed a poor clinical outcome after 90 days (41 %). Multivariable logistic regression analysis showed that older age (p = 0.033), higher admission NIHSS (p=0.009), lower admission ASPECTS (p=0.005), a pre-existing cardiovascular disease (p=0.017), and multiple passes for complete reperfusion (p=0.030) had an independent impact on unfavorable outcome. ConclusionsOlder age, higher NIHSS upon admission, lower ASPECTS upon admission, cardiovascular comorbidities and multiple passes for complete reperfusion are predictors for poor neurological long-term outcome despite complete reperfusion.

Association of pre-existing cardiovascular disease with administration of fluoropyrimidine chemotherapy in patients with gastrointestinal malignancies

ObjectiveFluoropyrimidine chemotherapy is a first-line treatment for many gastrointestinal (GI) cancers, however, cardiotoxicity concerns may limit administration in patients with pre-existing cardiovascular disease (CVD). This study investigated the association of...

SELECT: Glucagon-like peptide-1 receptor agonist in obese patients with cardiovascular disease in the absence of diabetes.

Obesity is a global epidemic affecting 2.5 billion people and is recognized as the fourth leading cause of global mortality. Obesity is characterized by excessive accumulation of body fat and is associated with a range of health consequences, including an elevated risk of cardiovascular disease (CVD). Glucagon-like peptide-1 (GLP-1) receptor agonists have been proven to reduce cardiovascular outcomes in patients with diabetes. Study and results: The SELECT trial was a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, conducted at 804 clinical sites in 41 countries. Patients were randomly assigned in a 1:1 ratio, to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular efficacy endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-first-event analysis. A total of 17,604 patients were recruited, with a mean age of 61.6 years and 72.3% males. The mean duration of exposure to semaglutide or placebo in the overall trial population was 34.2±13.7 months. The primary CVD endpoint occurred in 6.5% (n=569) of the semaglutide group and 8% (n=701) in the placebo group (hazard ratio, 0.80; 95% CI, 0.72 to 0.90; P<0.001). There was also a significant reduction of 9.39% in body weight among the patients taking semaglutide over 104 weeks after randomization versus 0.88% among the placebo group. Semaglutide reduces the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in obese and overweight non-diabetic patients with preexisting cardiovascular disease.

Association of accelerometer-derived physical activity with all-cause and cause-specific mortality among individuals with cardiovascular diseases: A prospective cohort study.

To investigate the association of accelerometer-measured intensity-specific physical activity (PA) with all-cause and cause-specific mortality among individuals with cardiovascular disease (CVD). In this prospective cohort study, 8,024 individuals with pre-existing CVD (mean age: 66.6 years, female: 34.1%) from the UK Biobank had their PA measured using wrist-worn accelerometers over a 7-day period in 2013-2015. All-cause, cancer, and CVD mortality was ascertained from death registries. Cox regression modelling and restricted cubic splines were used to assess the associations. Population-attributable fractions (PAFs) were used to estimate the proportion of preventable deaths if more PA were undertaken. During an average of 6.8 years of follow-up, 691 deaths (273 from cancer and 219 from CVD) were recorded. An inverse non-linear association was found between PA duration and all-cause mortality risk, irrespective of PA intensity. The hazard ratio (HR) of all-cause mortality plateaued at 1800 minutes/week for light-intensity PA (LPA), 320 minutes/week for moderate-intensity PA (MPA) and 15 minutes/week for vigorous-intensity PA (VPA). The highest quartile of PA associated lower risks for all-cause mortality, with HRs of 0.63 (95% confidence interval [CI]: 0.51-0.79), 0.42 (0.33-0.54) and 0.47 (0.37-0.60) for LPA, MPA, and VPA, respectively. Similar associations were observed for cancer and CVD mortality. Additionally, the highest PAF were noted for VPA, followed by MPA. We found an inverse non-linear association between all intensities of PA (LPA, MPA, VPA, and MVPA) and mortality risk in CVD patients using accelerometer-derived data, but with larger magnitude of the associations than that in previous studies based on self-reported PA.

Pre-Existing Cardiovascular Disease and Post-Acute Sequalae of SARS-CoV-2

Pre-Existing Cardiovascular Disease and Post-Acute Sequalae of SARS-CoV-2

COVID-19 in patients with pre-existing cardiovascular disease: a series of cases during the fourth epidemiologic wave in Mexico City

SARS-CoV-2 infection induces an immune response that causes excessive inflammation damaging cardiac tissue and vascular endothelium. The objective of this study is to review a series of cases of hospitalized patients with pre-existing cardiac disease to describe the clinical behavior and highlight the low frequency of morbidity and mortality. Retrospective study of 17 patients with a confirmed diagnosis of COVID-19 by polymerase chain reaction test or antigen test, a history of cardiovascular disease with or without comorbidities, and a history of at least one dose of the vaccine for COVID-19, during the period between December 30, 2021 and March 17, 2022 at the Ignacio Chávez National Institute of Cardiology in Mexico City. The most frequent cardiac pathology was acute myocardial infarction (31.25%) and the most common arrhythmia was atrial fibrillation (25%). The median number of days of hospital stay was 10 days (interquartile range: 4-14). Regarding the outcomes, 94% of the patients were discharged due to clinical improvement, and only one patient died during his hospitalization. It is crucial to continue investigating SARS-CoV-2 effects in patients pre-existing heart disease and in those with persistent symptoms after infection. This will allow the development of more effective strategies for the treatment and prevention of cardiovascular complications associated with COVID-19.

Pre-existing cardiovascular disease in the intensive care population: a national data study in scotland

Abstract Introduction/Background Each year, nearly 17,000 patients are admitted to Intensive Care Units (ICU) in Scotland. Forty percent of these patients suffer from one or more pre-existing co-morbidity. Pre-existing co-morbid disease is a known risk factor for readmission to ICU, increased healthcare use, protracted recovery and reduced health-related quality of life. Nonetheless, it is unknown which group of patients is most affected. Given the heterogeneity of the ICU population and in consideration of more "targeted" care, understanding the influence of co-morbidities and identification of specific patient groups is necessary. In tandem, the association between cardiovascular disease and critical illness is under researched. Yet it is known that 20% of ICU patients suffer from cardiovascular disease (CVD), with some evidence to suggest CVD is linked to increased 5-year mortality in this group of patients. Purpose To understand the prevalence of pre-existing CVD and other pre-existing co-morbidities in the critically ill population and to determine the influence of pre-existing CVD on hospital readmission rates (within one year of index hospital discharge). Methods This study is a retrospective cohort analysis using routinely collected data on ICU admissions between 2010 and 2019 in Scotland. Following public benefit and privacy panel (PBPP) approval and university integrity committee review, data was accessed via a secure National Safe Haven platform. Demographic data are presented alongside correlation analysis. Results More than 100,000 patients were admitted to ICU between 2010 and 2019. Of these patients, around 10% suffered from pre-existing CVD, with 30% suffering from any co-morbid disease, as defined by Charlson Co-morbidity index. It was identified that around 10% of ICU patients were readmitted to ICU within one year and a further 20% readmitted to hospital within one year. Of those patients readmitted to ICU, 10% suffer from pre-existing CVD. Conclusion This study identified that CVD is prevalent amongst the critically ill population with many experiencing a further admission to ICU. Despite this, little is known about the follow-up care provided to these patients with regards to managing CVD.

Anthracycline therapy induces an early decline of cardiac contractility in low-risk patients with breast cancer

AimsCancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors.We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625).Methods and resultsWe enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping.Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired.ConclusionIn every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events.Graphical Reduced myocardial contractility in low-risk patients receiving anthracycline-based cancer therapy. This study included 59 otherwise healthy women with primary breast cancer undergoing anthracycline-based chemotherapy. CMR was performed at baseline, directly and 12 months after cancer therapy. A decline in left ventricular function was observed in every single patient accompanied by transient edema. More than 50% were diagnosed with cancer therapy related cardiovascular dysfunction. LVEF: left ventricular function, CTRCD: cancer therapy related cardiovascular dysfunction, GLS = Global longitudinal strain, hs-TnT= high sensitive Troponin T, NT-pro BNP = NT-pro brain natriuretic peptide

Pathomechanistic Synergy Between Particulate Matter and Traffic Noise-Induced Cardiovascular Damage and the Classical Risk Factor Hypertension.

In all modern urbanized and industrialized societies, non-communicable diseases, like cardiovascular disease (CVD), are becoming a more important cause of morbidity and mortality. Classic risk factors for CVDs, such as hypertension, are reinforced by behavioral risk factors, like smoking and diet, and environmental risk factors, like transportation noise and air pollution. Both transportation noise and air pollution have individually been shown to increase the risk for CVD in large cohorts. Insights from animal studies have revealed pathophysiologic mechanisms by which these stressors influence the cardiovascular system. Noise primarily causes annoyance and sleep disturbance, promoting the release of stress hormones. Air pollution primarily damages the lung, where it causes local inflammation and an increase in oxidative stress, which can propagate to the circulation and remote organs. Both noise and air pollution converge at the vascular level, where the inflammatory state and oxidative stress cause dysfunction in vascular signaling and promote atherosclerotic plaque formation and thrombosis. Both inflammation and oxidative stress are key aspects of traditional cardiovascular risk factors, such as arterial hypertension. The similarities among the mechanisms of environmental risk factor-induced CVD and hypertension indicate that a complex interplay between them can drive the onset and progression of CVDs, leading to synergistic health impacts. Our present overview of the negative effects of noise and air pollution on the cardiovascular system provides a mechanistic link to the traditional CVD risk factor, hypertension, which could be used to protect patients with pre-existing CVD better.

Cardiovascular diseases as risk factors of post-COVID syndrome: a systematic review

BackgroundA growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors.MethodsFollowing the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (≥ 18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834).ResultsIn total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality.ConclusionOur review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients’ disease progression.

Physical Health in Patients with Post-COVID-19 6 and 12 Months after an Inpatient Rehabilitation: An Observational Study.

Background: Rehabilitation is an effective and feasible approach for post-COVID patients to improve physical health. However, knowledge regarding the long-term impact of rehabilitation on the physical health of these patients is lacking. Methods: Changes in physical health of 127 patients with COVID-19 as an occupational disease or work accident were assessed in a longitudinal observational study. Post-COVID symptoms, functional status, functional exercise capacity, endurance capacity, physical performance, quadricep strength, handgrip strength, motor balance ability, and self-reported physical performance were examined at the beginning as well as 6 and 12 months after the rehabilitation. Group differences concerning sex, age, acute COVID status, comorbidities prior to COVID-19, and aftercare interventions were also analysed. Results: Even 12 months after rehabilitation, the prevalence of post-COVID symptoms (28.6-94.7%) remained remarkably high in the study population. Significant improvements in various aspects of physical health were observed 6 (r = 0.288-0.755) and 12 months (r = 0.189-0.681) after the rehabilitation. Participants demonstrated enhanced endurance, strength, and balance function, as well as improvement in subjective physical ability. Significant group differences were observed between younger and older patients, those with mild-moderate and severe-critical COVID-19, and patients with and without pre-existing cardiovascular disease, metabolic disease, psychological disease, neuro-sensory disease, musculoskeletal disease, and exercising in an outpatient group. Conclusions: The study identifies persistent challenges in COVID-19 recovery, despite significant improvements in physical health 6 and 12 months after rehabilitation. Further research and the implementation of standardised approaches are required to enhance the outcomes of post-COVID rehabilitation, with a focus on developing personalised care strategies for long-term recovery.

Electrolytes, Zinc and Vitamin D3 in COVID-19 Patients with Cardiovascular Complications.

COVID-19 is strongly linked to cardiovascular disease, with direct myocardial injury and systemic inflammation as common mechanisms. Pre-existing or infection-induced cardiovascular disease worsens the outcomes for COVID-19 patients. To estimate the serum electrolytes (Na+, K+, Ca++, Zn) and vitamin D3, the study depended on ichroma ii device for Vitamin D3 and Chemistry Analyzer for electrolytes in patient samples. A study was conducted on 192 individuals diagnosed with COVID-19, including 35 critical cases, 53 severe cases, 54 moderate cases, and 50 individuals in a control group. The age group with the highest prevalence of infection was between 50‒69 years, while the lowest prevalence was observed in those under 30 years. The study found significant decreases in calcium, potassium, sodium, zinc, and vitamin D3 levels among COVID-19 patients compared to the control group. Zinc and vitamin D3 levels showed a significant correlation with sex, with males experiencing a decline in zinc levels and females having lower vitamin D3 levels. The concentration of calcium, sodium, and zinc showed a negative correlation with age, with older patients having the lowest levels. COVID-19 patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease also had a detrimental impact on electrolyte levels, zinc, and vitamin D3, with critical cases showing the lowest levels. The complications such as heart failure were associated with lower levels of potassium, sodium, and zinc. In conclusion, the study revealed significant associations between COVID-19 and decreased electrolyte levels, zinc, and vitamin D3. Sex and age were found to be correlated with these markers. Patients with chronic cardiac issues and high blood pressure exhibited the lowest levels of these markers. The severity of the disease was also linked to lower electrolyte levels, zinc, and vitamin D3. Complications such as heart failure were associated with decreased levels of potassium, sodium, and zinc.

Cardiovascular complications in the course of COVID-19 - lessons learned and implications for the future care of patients with viral respiratory diseases: Data from a single center retrospective observational study

BackgroundFactors associated with cardiovascular complications of COVID-19 remain understudied. ObjectivesHere we investigate the occurrence and risk factors of arrythmias, myocardial infarction and/or stroke, and thromboembolism in the course of COVID-19. MethodsWe have performed an observational study with prospectively designed data collection. Data of patients diagnosed with COVID-19 who were admitted from March 6th 2020 to November 30th 2021 in our Hospital were analyzed. Logistic regression was used to identify variables associated with the odds of early hospital death due to COVID-19. ResultsFourteen-point three percent of 1964 patients had cardiovascular complications, 6.36 % arrhythmias, 5.5 % thromboembolic events and 2.39 % myocardial infarction and/or stroke. Factors independently increasing the odds of arrhythmia were older age (OR=1.49 [95 % CI: 1.17–1.92], p = 0.02), longer time between admission and the first onset of symptoms (1.02 [0.99–1.05], p = 0.049), concomitant atrial fibrillation/flutter (2.84 [1.37–5.70], p = 0.004), nicotinism (2.49 [1.37–4.49], p = 0.002), and eGFR<60 ml/min/1.73m2 (2.44 [1.08–5.59], p = 0.033). Factors independently increasing the odds of myocardial infarction and/or stroke were dementia (4.55 [0.97–19.3], p = 0.044), hemiplegia (12.67 [3.12–46.1], p < 0.001), nicotinism (3.36 [1.30–10.4], p = 0.013) and higher C-reactive protein concentration (1.01 [1.00–1.01], p = 0.040). Factors independently increasing the odds of thromboembolic events were longer hospitalization (1.08 [1.05–1.10], p < 0.001) and higher d-dimers (1.04 [1.02–1.05], <0.001). ConclusionsThe risk of cardiovascular complications was especially pronounced in patients with older age, pre-existing cardiovascular disease and more sever pneumonia at presentation to care. This underlines the importance of close and careful clinical follow-up in the course of COVID-19 for specific patients’ populations, including a pro-active approach in diagnosis.

Thermal Influence on the Heart: The Impact of Hot Weather on Cardiovascular Conditions.

Dear Editor, We are cognisant of the fact that cardiovascular diseases (CVDs) have a considerable impact on public healthcare systems. Cardiovascular disorders rank as the primary global reason of fatality, claiming an estimated 17.9 million lives in 2019, which equates to 32% of all global fatalities. The majority of these deaths, around 85 percent, result from heart attacks and strokes. Low- and middle-income countries tolerate the brunt of heart-related fatalities, accounting for over three quarters of all deaths attributed to these conditions. Additionally, out of the 17 million premature deaths caused by noncommunicable diseases in 2019, CVDs were responsible for 38 percent.1 The prevailing cardiovascular risk factors encompass increasing age, hypertension (commonly referred to as a double-edged sword), diabetes mellitus, tobacco use, obesity, dyslipidaemia, and stress.1,2 A sedentary lifestyle together with poor eating habits have also led to an increased rate of CVS-related illnesses.1 Often overlooked as a risk factor, experiencing high temperatures significantly adds to the increased occurrence of cardiovascular diseases. Multiple studies support the connection between extreme temperatures and heightened cardiovascular risks.2-5 Being exposed to higher temperatures can lead to intravascular volume depletion, haemoconcentration, a hypercoagulable state, electrolyte imbalance, and raised sympathetic activity, placing substantial stress on the heart, especially in individuals with pre-existing cardiovascular disease.3 To investigate cardiovascular mortality associations with extremes of temperatures, Barrak Alahmad et al. assembled daily counts of specific cardiovascular causes of death from 567 cities across 5 continents in overlapping periods ranging from 1979 to 2019, and the city-specific daily ambient temperatures were noted. The findings indicated that higher temperature extremes (99th percentile for heat and 1st percentile for cold) were linked to an increased probability of mortality from various cardiovascular conditions, including ischaemic heart disease, stroke, and heart failure.4 In a case-crossover study conducted using the England and Wales MINAP database, involving 24,861 participants (hospital admissions for myocardial infarction) during the warmest months (June to August) from 2003 to 2009, it was found that each 1-degree Celsius increase in temperature beyond the established threshold of 20 °C temporarily increased the risk of heart attack by 1.9 percent.5 The cardiovascular-related illness and fatalities are quite prevalent in Pakistan. Pakistan due to her geographical location, usually encounters summer temperatures ranging from 45 to 55 degrees Celsius across most areas of the country. ---Continue

Epidemiologic Features of Recovery From SARS-CoV-2 Infection

Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking. To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension. This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024. Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications. Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups. Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease. This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

Impact of Azithromycin on the Predisposition to Cardiac Arrhythmias in Adult Patients: A Systematic Review

Background: Azithromycin is a macrolide antibiotic that can lead to QT interval prolongation, which may trigger ventricular tachycardia, also known as torsades de pointes (TdP), the most common cardiac arrhythmia associated with these drugs. All macrolides are linked to QTc interval prolongation, with apparently higher risk with erythromycin and clarithromycin compared to azithromycin. Macrolides can extend QT and QTc intervals and cause cardiac arrhythmias, including TdP, ventricular tachycardia, and ventricular fibrillation, through their affinity for binding to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of TdP. However, it is crucial to assess the risk-benefit ratio of prescribing azithromycin, especially in patients with preexisting cardiovascular disease or taking concomitant medications that prolong the QT interval. Objectives: The aim of this study is to determine whether azithromycin is genuinely associated with the occurrence of ventricular arrhythmias in adult patients. Materials and Methods: This systematic review is based on meticulous searching across Medline and Google Scholar databases, analysis of publications, and synthesis of available evidence regarding the risk of arrhythmias with the use of azithromycin. Results: We reviewed 6 articles that met the criteria, including 20.510.653 patients and 66 articles. While some studies suggest an increased risk of ventricular arrhythmias in certain subgroups of patients, others have not found a significant association between azithromycin and these arrhythmias. These discrepancies could be attributed to differences in the definition of arrhythmias, the duration of follow-up, or the characteristics of the groups of patients evaluated. The results point toward the need for a more thorough risk assessment before initiating this antibiotic in adult patients, especially those with known cardiovascular risk factors or those with a history of heart disease. Several risk factors, such as hypokalemia, pre-existing heart conditions, and concomitant use of other QT-prolonging medications, have been identified as increasing vulnerability to macrolide-induced arrhythmias. Conclusion: The results of the systematic review and cohort studies analyzed consistently suggest an association between the use of azithromycin and an increased risk of developing ventricular arrhythmias. This risk appears to be most evident in the elderly, with different studies showing variations in the magnitude of the risk. It is crucial to evaluate the risks and benefits of these antibiotics in each clinical situation, considering the information provided by observational studies and systematic reviews