Abstract
Aims
The association of body weight and weight change with mortality and cardiovascular (CV) outcome in patients with diabetes mellitus (DM) is not clearly established. We assessed the ...relationship between weight, weight change, and outcomes in patients with established CV risk factors and type 2 DM or pre-diabetes.
Methods and results
A total of 12 521 participants from the ORIGIN trial were grouped in BMI categories of low body weight body mass index (BMI) < 22 kg/m2 normal (22–24.9), overweight (25–29.9), obesity Grades 1–3 (30–34.9, 35–39.9, ≥40 kg/m2, respectively). Outcome variables included total and CV mortality and composite outcomes of CV death, non-fatal stroke, or myocardial infarction plus revascularization or heart failure hospitalization. Follow-up was 6.2 years (interquartile range 5.8–6.7 years). After multivariable adjustment, lowest risks were seen in patients with overweight and mild obesity for total mortality overweight: hazard ratio (HR) 0.80 (95% confidence interval (CI) 0.69–0.91); obesity Grade 1: HR 0.82 (0.71–0.95), both P < 0.01) and CV mortality overweight: HR 0.79 (0.66–0.94); obesity Grade 1: 0.79 (0.65–0.95), all compared to patients with normal BMI, P < 0.05. Obesity of any severity was not associated with higher mortality. Low body weight was related to higher mortality HR 1.28 (1.02–1.61); CV mortality: HR 1.34 (1.01–1.79), P < 0.05. A continued 2-year weight loss was associated with higher risk of mortality HR 1.32 (1.18–1.46), P < 0.0001 and CV mortality HR 1.18 (1.02–1.35), compared to patients without weight loss, P < 0.05. In turn, weight gain was not related to any adverse outcome.
Conclusion
Obesity in patients with DM or pre-diabetes and CV risk profile was not associated with higher mortality or adverse CV outcome. The lowest mortality risk was seen in patients with overweight and moderate obesity (BMI 25–35 kg/m2). Weight loss was an independent risk factor for higher mortality compared to no weight loss.
Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at ...intermediate risk and with lower blood pressure is unclear.
In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.
The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval CI, 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events ...substantially.
In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval CI, 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with ...elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease.
In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.
The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval CI, 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants 4.4% in the rosuvastatin group and in 363 participants 5.7% in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005).
Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).
In this study, we aim to evaluate dietary supplement and complementary and alternative medicine (CAM) use in individuals with depressive symptoms. Furthermore, we conducted a comparative analysis of ...the usage of these agents among individuals with depressive symptoms, differentiating between those who were using antidepressants and those who were not. Additionally, we compared individuals with depressive symptoms who were not using antidepressants with participants who did not have depressive symptoms as well as individuals with depressive symptoms who were using antidepressants with individuals without depressive symptoms.
The National Health and Nutrition Examination Survey 2007-2018 data was collected. Depressive symptoms were assessed using patient health questionnaire-9. Dietary supplement and antidepressants use was evaluated using Dietary Supplement Use and Prescription Medications Questionnaires.
31,445 participants, with 2870 (8.05%) having depressive symptoms were included. Participants with depressive symptoms had significantly lower odds of dietary supplement use compared with those without depressive symptoms (aOR = 0.827, 95% CI: 0.700,0.977, p = 0.026). Participants with depressive symptoms who were using antidepressants had significantly higher odds of dietary supplement (aOR = 1.290, 95% CI: 1.038,1.604, p = 0.022) compared with participants with depressive symptoms who were not using antidepressants. Furthermore, Participants with depressive symptoms who weren't using antidepressants had significantly lower odds of dietary supplement use (aOR = 0.762, 95% CI: 0.632,0.918, p = 0.005) compared with participants without depressive symptoms. In individuals with treated depressive symptoms compared to those without depressive symptoms, CAM use was significantly lower (aOR = 0.763, 95% CI = 0.598,0.973, p = 0.030).
Individuals with depressive symptoms have lower odds of dietary supplement use. Further studies are needed to replicate these findings and examine the underlying mechanisms for this association.
Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or ...nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial.
This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (
= 11,495). Severe and nonsevere hypoglycemic events were collected prospectively during a median follow-up time of 6.2 years. Incident cognitive dysfunction was defined as either reported dementia or an MMSE score of <24. The hazard of at least one episode of severe or nonsevere hypoglycemia for incident cognitive dysfunction (i.e., the dependent variable) from the time of randomization was estimated using a Cox proportional hazards model after adjusting for baseline cardiovascular disease, diabetes status, treatment allocation, and a propensity score for either form of hypoglycemia.
This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio HR 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment.
Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.
Higher education is associated with reduced depressive symptoms and requires investment without guaranteed employment. It remains unclear how sex and employment status together contribute to the ...association between mental health and educational attainment. This study investigated the role of sex and employment status together in the associations of 1) depressive symptoms and 2) suicidal ideation with education.
Using 2005-2018 National Health and Nutrition Examination Survey data, cross-sectional analyses were conducted on individuals ≥20 years who completed the depression questionnaire and reported their employment status and highest level of education. Survey-weighted multivariable logistic regression models were used to explore how depressive symptoms and suicidal ideation are associated with educational attainment in an analysis stratified by sex and employment status. To account for multiple testing, a significance level of a < 0.01 was used.
Participants (n = 23,669) had a weighted mean age of 43.25 (SD = 13.97) years and 47% were female. Employed females (aOR = 0.47, 95% CI 0.32, 0.69), unemployed females (aOR = 0.47, 95% CI 0.29, 0.75), and unemployed males (aOR = 0.31, 95% CI 0.17, 0.56) with college education had reduced odds of depressive symptoms compared to those with high school education. Employed females with college education also had reduced suicidal ideation odds compared to those with high school education (aOR = 0.41, 95% CI 0.22, 0.76).
Females demonstrated significant associations between depressive symptoms and education, regardless of employment status, whereas males demonstrated an association only if unemployed. Employed females, in particular, demonstrated a significant association between suicidal ideation and education. These findings may inform future research investigating the underlying mechanisms and etiology of these sex-employment status differences in the association between mental health and education.
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a ...systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Groundwater salinization in coastal aquifers because of seawater intrusion has raised serious concerns worldwide since it deteriorates the quality of drinking water and thereby threatens sustainable ...economic development. In particular, this problem has been a cause of growing concern in the western coastal regions of South Korea. In this paper, we review studies of seawater intrusion in western coastal regions of South Korea conducted over the past 20 years, particularly focusing on studies reported in international journals. We summarize the study locations, methods used, and major findings from individual and regional-scale studies. General methods used to identify and interpret seawater intrusion and subsequent geochemical processes are also presented. On the basis of insights gleaned from the previous studies, future research needs are discussed.
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