Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease

Coordinated molecular responses are key to effective initiation and resolution of both acute and chronic inflammation. Vascular inflammation plays an important role in initiating and perpetuating atherosclerotic disease, specifically at the site of plaque and subsequent fibrous cap rupture. Both men and women succumb to this disease process, and although management strategies have focused on revascularization and pharmacological therapies in the acute situation to reverse vessel closure and prevent thrombogenesis, data now suggest that regulation of host inflammation may improve both morbidity and mortality, thus supporting the notion that prevention is better than cure. There is a clear sex difference in the incidence of vascular disease, and data confirm biological differences in inflammatory initiation and resolution between men and women. This article reviews contemporary opinions describing the sex difference in the initiation and resolution of inflammatory responses, with a view to explore potential targets for pharmacological intervention.

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Medical Management of Vascular Disease

DeckerMed Surgery ◽

10.2310/surg.2146 ◽

2013 ◽

Author(s):

Deepak G. Nair ◽

Russell H. Samson

Keyword(s):

Vascular Disease ◽

Medical Management ◽

Lifestyle Modification ◽

Disease Process ◽

Antiplatelet Agents ◽

Aortic Aneurysms ◽

Lipid Lowering ◽

Pharmacological Intervention ◽

Bile Acid Sequestrants ◽

Artery Disease

Although surgeons may be able to bypass or open blocked arteries and replace aneurysms with minimally invasive surgery, patients continue to die from the other cardiovascular consequences of vascular disease. Surgeons must become more involved in the nonsurgical treatments of peripheral artery disease (PAD). A good understanding of the role of lipids in atherosclerosis is critical but surgeons must also recognize the threats of diabetes; smoking; hypertension; and hyperlipidemia on PAD. Treatments, including lifestyle modification, diet, exercise, and the influence of lipid-lowering agents is described. Medications that can alter PAD are described in detail and include statins; fibrates; niacin; bile acid sequestrants; ezetimibe; and antiplatelet agents. Side effects and monitoring is also described. Although much of the review covers the general principles of medical management of patients with PAD, components of this overall disease process are also provided and include pharmacological intervention for claudication; stroke; aortic aneurysms; and nonatherosclerotic vascular disease. This review contains 2 figures, 2 tables, and 181 references.

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The Relationship of Compliance with Coping Strategies and Self-Esteem

European Journal of Psychological Assessment ◽

10.1027//1015-5759.19.2.117 ◽

2003 ◽

Vol 19 (2) ◽

pp. 117-123 ◽

Cited By ~ 40

Author(s):

Gisli H. Gudjonsson ◽

Jon Fridrik Sigurdsson

Keyword(s):

Sex Differences ◽

Coping Strategies ◽

Multiple Regression ◽

Sex Difference ◽

Test Scores ◽

Self Esteem ◽

Stressful Situation ◽

Men And Women ◽

Relationship Of ◽

The Relationship

Summary: The Gudjonsson Compliance Scale (GCS), the COPE Scale, and the Rosenberg Self-Esteem Scale were administered to 212 men and 212 women. Multiple regression of the test scores showed that low self-esteem and denial coping were the best predictors of compliance in both men and women. Significant sex differences emerged on all three scales, with women having lower self-esteem than men, being more compliant, and using different coping strategies when confronted with a stressful situation. The sex difference in compliance was mediated by differences in self-esteem between men and women.

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Sex Differences in Time Production Revisited

Journal of Individual Differences ◽

10.1027/1614-0001/a000059 ◽

2012 ◽

Vol 33 (1) ◽

pp. 35-42 ◽

Cited By ~ 22

Author(s):

Joseph Glicksohn ◽

Yamit Hadad

Keyword(s):

Sex Differences ◽

Individual Differences ◽

Sex Difference ◽

Absolute Error ◽

Internal Clock ◽

Target Duration ◽

Log P ◽

Men And Women ◽

Time Production ◽

T Score

Individual differences in time production should indicate differences in the rate of functioning of an internal clock, assuming the existence of such a clock. And sex differences in time production should reflect a difference in the rate of functioning of that clock between men and women. One way of approaching the data is to compute individual regressions of produced duration (P) on target duration (T), after log transformation, and to derive estimates for the intercept and the slope. One could investigate a sex difference by comparing these estimates for men and women; one could also contrast them by looking at mean log(P). Using such indices, we found a sex difference in time production, female participants having a relatively faster internal clock, making shorter time productions, and having a smaller exponent. The question is whether a sex difference in time production would be found using other methods for analyzing the data: (1) the P/T ratio; (2) an absolute discrepancy (|P-T|) score; and (3) an absolute error (|P-T|/T) score. For the P/T ratio, female participants have a lower mean ratio in comparison to the male participants. In contrast, the |P-T| and |P-T|/T indices seem to be seriously compromised by wide individual differences.

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The impact of vildagliptin on the daily glucose profile and coronary plaque stability in impaired glucose tolerance patients with coronary artery disease: VOGUE—A multicenter randomized controlled trial

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01902-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hiroyuki Yamamoto ◽

Akihide Konishi ◽

Toshiro Shinke ◽

Hiromasa Otake ◽

Masaru Kuroda ◽

...

Keyword(s):

Coronary Artery Disease ◽

Controlled Trial ◽

Control Group ◽

Randomized Controlled ◽

Fibrous Cap ◽

Multicenter Randomized Controlled Trial ◽

The Mean ◽

Artery Disease ◽

Fibrous Cap Thickness ◽

The Impact

Abstract Background The impact of reduction in glycemic excursion on coronary plaques remains unknown. This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). Methods This was a multicenter, randomized controlled trial including CAD patients with IGT under lipid-lowering therapy receiving either vildagliptin (50 mg once a day) or no medication (control group) regarding glycemic treatment. The primary endpoint was changes in the minimum fibrous cap thickness and lipid arc in non-significant native coronary plaques detected by optical coherence tomography at 6 months after intervention. Glycemic variability expressed as the mean amplitude of glycemic excursion (MAGE) measured with a continuous glucose monitoring system was evaluated before and 6 months after intervention. Results A total of 20 participants with 47 lesions were allocated to either the vildagliptin group (10 participants, 22 lesions) or the control group (10 participants, 25 lesions). The adjusted difference of mean changes between the groups was − 18.8 mg/dl (95% confidence interval, − 30.8 to − 6.8) (p = 0.0064) for the MAGE (vildagliptin, − 20.1 ± 18.0 mg/dl vs. control, 2.6 ± 12.7 mg/dl), − 22.8° (− 40.6° to − 5.1°) (p = 0.0012) for the mean lipid arc (vildagliptin, − 9.0° ± 25.5° vs. control, 15.8° ± 16.8°), and 42.7 μm (15.3 to 70.1 μm) (p = 0.0022) for the minimum fibrous cap thickness (vildagliptin, 35.7 ± 50.8 μm vs. control, − 15.1 ± 25.2 μm). Conclusions Vildagliptin could reduce the MAGE at 6 months and may be associated with the decreased lipid arc and increased minimum FCT of the coronary plaques in CAD patients with IGT as compared with the control group. These findings may represent its potential stabilization effect on coronary plaques, which are characteristic in this patient subset. Trial registration Registered in the UMIN clinical trial registry (UMIN000008620), Name of the registry: VOGUE trial, Date of registration: Aug 6, 2012, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000010058

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The Sex Differences in Uveal Melanoma: Potential Roles of EIF1AX, Immune Response and Redox Regulation

Current Oncology ◽

10.3390/curroncol28040245 ◽

2021 ◽

Vol 28 (4) ◽

pp. 2801-2811

Author(s):

Feng Liu-Smith ◽

Chi-Yang Chiu ◽

Daniel L. Johnson ◽

Phillip Winston Miller ◽

Evan S. Glazer ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Sex Difference ◽

Uveal Melanoma ◽

Disulfide Bond ◽

Bond Formation ◽

Disulfide Bond Formation ◽

Men And Women ◽

Copy Numbers ◽

Differential Gene

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM.

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Pharmacological Management of Steroid-Induced Psychosis: A Review of Patient Cases

Journal of Pharmacy Technology ◽

10.1177/8755122520978534 ◽

2020 ◽

pp. 875512252097853

Author(s):

Grace Huynh ◽

Justin P. Reinert

Keyword(s):

Adverse Drug Events ◽

Data Extraction ◽

Management Strategies ◽

Pharmacological Intervention ◽

Symptom Presentation ◽

Pharmacological Management ◽

Diagnostic And Statistical Manual ◽

Study Selection ◽

Cord Injury ◽

Male Patients

Objective: To review the efficacy and safety of medications used in the management of steroid-induced psychosis. Data Sources: A comprehensive literature search was conducted using PubMed, MEDLINE, ProQuest, and Scopus between May and October 2020 using the following search terminology: “steroid-induced psychosis” OR “corticosteroid-induced psychosis.” Study Selection and Data Extraction: Definitive cases, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, were included in this review. Geriatric patients >65 years of age, those with a confounding neurological condition such as a traumatic brain or spinal cord injury, or those with active malignancy were excluded. Data Synthesis: A total of 13 patient cases were included in this review, representing 8 male patients and 5 female patients. The mean age at symptom presentation was 42.5 years. Six patients presented with delusions, 5 presented with hallucinations, and 2 presented with both manifestations; 12 patients were managed with an antipsychotic, with haloperidol being the most commonly prescribed, followed by risperidone. One patient was managed with lithium and clonazepam alone. All patients returned to their psychological baseline upon the discontinuation or decreased dose of steroids in combination with Pharmacological intervention, though the time to resolution of symptoms varied significantly. No notable adverse drug events associated with treatments were reported. Conclusions: Steroid-induced psychosis is a serious adverse effect of corticosteroid therapy; however, management strategies that combine a dose reduction or elimination of steroids, in combination with an antipsychotic medication, are effective in resolving this syndrome.

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