Circadian Cadence and NR1D1 Tune Cardiovascular Disease

Cardiovascular (CV) disease (CVD) is the major health burden and cause of death for women. Marked disparities exist in CVD diagnosis, prevention, and treatment between women and men – as well as lack of female-specific data. Population, physiologic, translational, and clinical trial studies of sex and gender differences in CVD [[Unable to Display Character: –]] even when only women are studied[[Unable to Display Character: –]] often do not collect relevant data specific to women that could inform study outcomes. The ISIS CVD Network of the Society for Women’s Health Research compiled an inventory of items specific for women across the lifespan, together with references for methods and strategies to gather and evaluate this information; some items comprise robust measures, others are in development. The objective is to enhance usefulness of CVD research data in understanding sex and gender differences, thereby optimizing healthcare delivery and outcomes for women. Included are hormonal variables (menstrual cycle phase, hormone levels) oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, measures of menopause, and menopausal hormone therapy, variables generally not collected in research studies, but essential to determine their role as sex-specific contributors to CV health and disease. Clear associations exist between reproductive health and CV health and disease. For example 25-33% of women experience complications of pregnancy that may precede and predispose to CVD. Vascular complications during pregnancy, antecedent risk factors and subsequent clinical CVD can be ascertained using medical records, birth registries, and/or maternal recall. Evaluating compilations of patient data with known hormonal or menopausal status using reference standards and patient data for PCOS could inform relationships to subsequent CV outcomes. Variables predominant among women that preferentially disadvantage them should be considered; e.g. psychosocial issues and elderly age. Depressive disorders are twice as common among women as men. They adversely affect CVD outcomes in women, yet the effect of reproductive life cycle and of hormonal fluctuations on depression and etiologic contributions of depression to CVD are inadequately explored. In addition to traditional CVD risk factors, diabetes mellitus, chronic inflammatory disorders, oxidative stress, vasomotor dysfunction, coronary microvascular disorders, and other novel risk variables that preferentially impact women should be explored. Along with increased enrollment of women in CVD research studies and analysis of clinical and genetic studies by sex, improvements and expansion of study design must include these understudied uniquely or predominantly female characteristics. This will enhance the quality and quantity of evidence-based medicine to guide CVD care in women and men thereby setting the stage for personalized approach to medicine.

Introduction

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Obstructive sleep apnea (OSA) is considered to be an important risk factor for the development of cardiovascular disease (CVD). This study aimed to develop and evaluate a machine learning approach with a set of features for assessing the 10-year CVD mortality risk of the OSA population. This study included 2,464 patients with OSA who met study inclusion criteria and were selected from the Sleep Heart Health Study. We evaluated the importance of potential features by mutual information. The top 9 features were selected to develop a random forest model. We evaluated the model performance on a test set (n = 493) using the area under the receiver operating curve with 95% confidence interval and confusion matrix. A random forest model awarded the highest area under the receiver operating curve of 0.84 (95% confidence interval: 0.78-0.89). The specificity and sensitivity were 73.94% and 81.82%, respectively. Sixty-three years old was a threshold for increased risk of 10-year CVD mortality. Persons with severe OSA had higher risk than those with mild OSA. This study demonstrated that a random forest model can provide a quick assessment of the risk of 10-year CVD mortality. Our model may be more informative for patients with OSA in determining their future CVD mortality risk. Li A, Roveda JM, Powers LS, Quan SF. Obstructive sleep apnea predicts 10-year cardiovascular disease-related mortality in the Sleep Heart Health Study: a machine learning approach. J Clin Sleep Med. 2022;18(2):497-504.

Prevention of Cardiovascular Disease in Persons with Type 2 Diabetes Mellitus: Current Knowledge and Rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

Preeclampsia: Exposing Future Cardiovascular Risk in Mothers and Their Children

The Effects of Dietary Sugars on Cardiovascular Disease and Cardiovascular Disease–Related Mortality: Finding the Sweet Spot

To explore the impct of heat wave on the daily deaths caused by cardiovascular disease and cerebrovascular diseases in Beijing. A case-crossover design was used to study the impact of 5 heat waves on the daily number of deaths from cardiovascular diseases and cerebrovascular disease, from Jan. 1, 1999 to Jun. 30, 2000. We also investigated the relationship between the heat wave and acute myocardial infarction deaths. The 7th day before death was chose as the indicator of self-control. The OR value of different lengths of risk period was calculated. The highest OR value and its corresponding risk period was used to reflect the impact of heat wave on daily number of cardiovascular and cerebrovascular disease deaths, lag days and their durations. There were five heat waves during the study period. The first heat wave lasted for 9 days, with the maximum temperature as 38.8°C and average humidity as 46.7%. The OR value for the cardiovascular disease death, cerebrovascular disease death and acute myocardial infarction death were 1.384 (95%CI: 1.128 - 1.697), 1.776 (95%CI: 1.456 - 2.167) and 1.276 (95%CI: 0.905 - 1.799) respectively. The second heat wave lasted 3 days, with the maximum temperature of 36.8°C and average humidity of 61.0%. The OR value for the three causes of death were 1.385 (95%CI: 0.678 - 2.826), 1.300 (95%CI: 0.726 - 2.329) and 2.000 (95%CI: 0.684 - 5.851) respectively. The third heat wave continued for 7 days, with the maximum temperature of 41.5°C, and average humidity of 58.5%. The OR value for the daily death counts caused by cardiovascular disease, cerebrovascular diseases and acute myocardial infarction were 2.613 (95%CI: 2.116 - 3.228), 2.317 (95%CI: 1.875 - 2.863) and 3.088 (95%CI: 2.098 - 4.546) respectively. The fourth wave lasted for 3 days, with the maximum temperature as 39.6°C and average humidity as 31.9%. The OR value for the deaths caused by cardiovascular disease, cerebrovascular diseases and acute myocardial infarction were 1.333 (95%CI: 0.724 - 2.457), 2.429 (95%CI: 1.007 - 5.856) and 3.333 (95%CI: 0.917 - 12.112) respectively. The fifth heat wave lasted for 4 days. The maximum temperature was 37.4°C, and the average humidity was 42.0% during the period. The OR value for daily death counts caused by cardiovascular disease, cerebrovascular disease and acute myocardial infarction were 2.333 (95%CI: 1.187 - 4.588), 1.727 (95%CI: 0.822 - 3.630) and 1.800 (95%CI: 0.603 - 5.371) respectively. (1) There were significant increases for daily death counts of both cardiovascular and cerebrovascular disease in Beijing during the heat wave and there appeared hysteresis effect as well. The lag phase of cardiovascular disease and cerebrovascular disease death was generally 2 - 4 days and acute myocardial infarction death usually was 0 - 2 days. (2) The rising of maximum temperature was greater at the beginning day of heat wave than the previous day, but the lag time was shorter, and the risk of death was greater, especially for the risk of deaths from cerebrovascular disease. (3) Fluctuations of daily maximum air temperature during the heat wave could increase the risk of death from cardiovascular disease.

To estimate the excess risk of cardiovascular and cerebrovascular diseases among individuals with ankylosing spondylitis (AS) in Quebec compared with the general population of Quebec. A retrospective cohort study was conducted using population-based administrative data from Quebec. The cohort included all adult individuals with at least 1 AS diagnosis on physician billing or hospital discharge records between 1996 and 2006. A comparison cohort was generated using a 1% random sample of individuals without AS. Cardiovascular and cerebrovascular diseases, and associated hospitalizations, were classified into 1 of 6 subcategories: congestive heart failure, valvular (aortic or nonaortic) heart disease, ischemic heart disease, cerebrovascular disease, or "other" cardiovascular disease. The age- and sex-stratified prevalence estimates, and standardized prevalence ratios, of cardiovascular or cerebrovascular disease in patients with AS, compared to that in the general population, were calculated. The AS cohort included 8,616 individuals diagnosed over the period 1996-2006. The prevalence of cardiovascular and cerebrovascular diseases increased with increasing age for all cardiovascular disease subgroups, and was similar for individuals of both sexes. Age- and sex-stratified prevalence ratios were highest in younger individuals with AS. The age- and sex-standardized prevalence ratios comparing the risk among those with AS to the risk in the general population were as follows: for aortic valvular heart disease 1.58 (95% confidence interval [95% CI] 1.31-1.91), for nonaortic valvular heart disease 1.58 (95% CI 1.43-1.74), for ischemic heart disease 1.37 (95% CI 1.31-1.44), for congestive heart failure 1.34 (95% CI 1.26-1.42), for "other" cardiovascular disease 1.36 (95% CI 1.29-1.44), for cerebrovascular disease 1.25 (95% CI 1.15-1.35), and for any hospitalization for a cardiovascular or cerebrovascular disease 1.31 (95% CI 1.22-1.41). Compared with the general population, patients with AS are at increased risk for many types of cardiovascular and cerebrovascular diseases, and are more likely to be hospitalized for these diseases. The excess risk is greatest in younger patients with AS.

The completion of the Human Genome Project has unleashed a wealth of human genomics information, but it remains unclear how best to implement this information for the benefit of patients. The standard approach of biomedical research, with researchers pursuing advances in knowledge in the laboratory and, separately, clinicians translating research findings into the clinic as much as decades later, will need to give way to new interdisciplinary models for research in genomic medicine. These models should include scientists and clinicians actively working as teams to study patients and populations recruited in clinical settings and communities to make genomics discoveries-through the combined efforts of data scientists, clinical researchers, epidemiologists, and basic scientists-and to rapidly apply these discoveries in the clinic for the prediction, prevention, diagnosis, prognosis, and treatment of cardiovascular diseases and stroke. The highly publicized US Precision Medicine Initiative, also known as All of Us, is a large-scale program funded by the US National Institutes of Health that will energize these efforts, but several ongoing studies such as the UK Biobank Initiative; the Million Veteran Program; the Electronic Medical Records and Genomics Network; the Kaiser Permanente Research Program on Genes, Environment and Health; and the DiscovEHR collaboration are already providing exemplary models of this kind of interdisciplinary work. In this statement, we outline the opportunities and challenges in broadly implementing new interdisciplinary models in academic medical centers and community settings and bringing the promise of genomics to fruition.

The National Heart, Lung, and Blood Institute (NHLBI) has a longstanding appreciation of the value of behavioral research. From the earliest days, when the concept of “coronary prone” behavior was introduced, to the growing recognition of the need for strategies to encourage health-promoting behaviors and lifestyles, to more recent efforts to incorporate health-related quality of life measures into our clinical studies, behavioral research has contributed much to our understanding of cardiovascular disease (CVD). Although still in its infancy, the application of this discipline to lung and blood diseases, sleep disorders, and transfusion medicine issues clearly offers much promise for advances in treatment and prevention. Acknowledging that many opportunities lie in biobehavioral research, in November 1995 the NHLBI convened the Task Force on Behavioral Research in Cardiovascular, Lung, and Blood Health and Disease to chart a course for future research efforts. Composed of national experts, it was charged to review the state of knowledge in biobehavioral research in cardiovascular, lung, and blood diseases and sleep disorders over the past 5 years; identify research opportunities; and develop a comprehensive plan, including scientific priorities, for NHLBI support of research on health and behavior for the next several years. During a series of meetings that spanned nearly 2 years, the task force worked to develop a report of its findings and conclusions. The report provides a detailed summary of accomplishments to date, highlights new scientific opportunities, and identifies specific recommendations for future research. The full text, with graphics, is available on the NHLBI Web site at http://www.nhlbi.nih.gov/nhlbi/sciinf/taskforc.htm. The synopsis that follows was excerpted from the executive summary of the task force report. The Institute is very pleased to have this task force report to guide its activities with respect to research on health and behavior. We are grateful to the task force chair, Dr …

This thesis focuses on cardiovascular (CV) disease (CVD) risk in rheumatoid arthritis (RA). Inflammation and CV risk factors are increased in RA patients. This population has a higher carotid intima-media thickness and more CV events than the general population and kynurenine (KYN) concentration levels are higher in RA patients compared to healthy controls. Therefore, in this thesis inflammation and CVD risk factors are investigated for increased risk of future RA development. RA and type2 diabetes (T2D) carotid intima-media thickness (CIMT) are compared and measurements of serum KYN for CVD, cancer and mortality are studied. First I tested the hypothesis that inflammation, CVD and CV risk factors are associated with increased risk of future RA development. Data from the Norwegian HUNT population health survey were obtained to compare groups with RA at baseline and follow-up (HUNT2 and HUNT3, n = 429) or follow up alone (HUNT3, n = 786), or without RA at both times (n = 33,567). Results showed female gender, age, smoking, body mass index (BMI), and history of previous CVD were associated with self-reported incident RA (previous CVD: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CVD were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.232.36)) or restricting the analysis to cases with hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.134-2.74)). History of previous CVD was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). I then compared the characteristics of CV risk and progression of CIMT in 78 RA patients from an outpatient Rheumatology Clinic and 212 patients with T2D who attended a community or hospital diabetes clinic in Brisbane. We found that the burden of risk varied between the 2 cohorts. RA patients were older, had a higher proportion of smokers, females and previous CVD. T2D patients had a higher body mass index (BMI), diastolic blood pressure, triglycerides, lower high density lipoprotein and a higher statin use. At baseline, CIMT measurements were similar in the RA and T2D cohorts. In an adjusted linear regression model, RA was significantly associated with lower CIMT at follow-up. Despite a shorter follow-up, 91 % of the T2D cohort had increased CIMT at follow-up compared to 54 % of the RA cohort. In the RA cohort, disease modifying anti-rheumatic drug (DMARD) use at baseline was associated with significantly lower CIMT values at follow-up. Finally we hypothesized that increased KYN in RA patients may predispose to CVD, infections and cancer. We measured KYN in 129 RA patients followed for 10 years for development of CVD, cancer and death. Median KYN concentrations were significantly higher in RA patients than in controls, but there was large overlap between groups. There were no variables in our data set that could explain the differences in KYN concentrations among the RA patients and KYN concentrations did not predict development of CVD, new malignancies or death. The number of pack-years of smoking was the only variable associated with death in logistic or Cox regression analysis. In summary, CVD risk factors are associated with increased risk of future RA development. The burden of risk varies in RA and T2D, and CIMT progression is slower for RA than for T2D. Although serum KYN concentrations are significantly higher in RA than in controls, they were not associated with CVD, new malignancies or death.

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Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Obesity has been described as the biggest health threat facing the Western world, and this statement will probably need to be revised shortly to encompass the entire world. The social and economic impact of this pandemic is enormous. Currently, a third of all Americans are obese, and this may reach