Effect of gender on the association between cumulative cardiovascular risk factors and depression: results from the US National Health and Nutrition Examination Survey.

Background: The comorbidity of cardiovascular disease (CVD) and depression has been well established, as depression usually presents simultaneously with CVD risk factors. However, the potential association between cumulative exposure to CVD risk and depression remains unclear, so we conducted the current investigation. To our knowledge, this is the first study that employs the cumulative risk model to examine the effect of CVD risk factors on depression using nationally representative population and gender, age and CVD status-stratified subpopulations. Aims: To systematically study the possible individual and cumulative effect of 18 CVD risk factors on depression. Methods: A cross-sectional, secondary analysis investigated associations between 18 CVD risk factors and depression. The interaction effect between CVD risk factors and age, gender and CVD status was also examined. Enrolment included 20 816 participants from the US National Health and Nutrition Examination Survey 2005-2016. Participants with Patient Health Questionnaire-9 scores over 15 or who were using an antidepressant were considered depressive; 18 known cardiovascular risk factors were incorporated in the present study. Results: At the individual risk factor level, smoking, drinking, living alone, sleep quality, body mass index, waist circumference and diabetes status had differential associations with depression risk according to the gender, age or CVD status of the participants. Most importantly, gender-stratified cumulative risk analysis indicated that similar depression risk was found in both genders with a small number of CVD risk factors (odds ratio (OR)adjusted=1.32; 95% confidence interval (CI): 0.87 to 1.99), but females had a significantly higher depression risk compared with males under high cumulative risk exposure (ORadjusted=2.86; 95% CI: 1.79 to 4.59). Conclusions: Clarifying the association of numerous CVD risk factors with depression according to gender, age and overall CVD status may be beneficial for risk stratification and the prevention of depression in clinical practice. Moreover, the observed novel evidence of high cumulative risk exposure-mediated gender disparities in depression risk may shed light on the underlying mechanism of females' greater vulnerability to depression.

The association between leukocyte telomere length and chronic obstructive pulmonary disease is partially mediated by inflammation: a meta-analysis and population-based mediation study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major health issues worldwide. Pathophysiological changes in COPD are mainly reflected in the deterioration of lung function with aging. METHODS: Considering that telomere length is a hallmark of biological aging, we first performed a meta-analysis to summarize the current knowledge about the relationship between telomere length and COPD and then employed individual-level data from the continuous National Health and Nutrition Examination Survey (NHANES) to investigate whether telomere length could reflect accelerated aging in COPD and serve as an independent predictor. A mediation study was further performed to examine whether the association between telomeres and COPD could be mediated by inflammation, as one of the most important etiologies and characteristics of COPD. RESULTS: The four studies included in our meta-analysis were with high heterogeneity (I2 = 95.7%, Phet < 0.001), and the pooled relative risk for COPD comparing the shortest tertile versus the longest tertile was 4.06 (95% CI = 1.38 to 11.96). Of the 6,378 subjects in the individual-level data analyses using NHANES, 455 were diagnosed with COPD, and multivariable-adjusted logistic regression also indicated that short telomere length was associated with COPD. Consistently, cubic regression spline analyses showed that long telomeres exhibited a significant association with a decreased risk of COPD. In the subsequent mediation analyses, C-reactive protein concentration, white blood cells count and blood neutrophil count, as inflammatory biomarkers, showed a significant indirect effect on the relationship between telomere length and COPD. CONCLUSION: Accelerated aging in COPD could be characterized by excessive telomere shortening, and inflammatory response might be involved in the underlying mechanisms of COPD pathogenesis promoted by short telomere length. Telomere length measurement may facilitate clinical translational research and targeted therapy of COPD.

Association Study of Genetic Variants in Calcium Signaling-Related Genes With Cardiovascular Diseases.

Background: Calcium ions (Ca2+) play an essential role in excitation-contraction coupling in the heart. The association between cardiovascular diseases (CVDs) and genetic polymorphisms in key regulators of Ca2+ homeostasis is well established but still inadequately understood. Methods: The associations of 11,274 genetic variants located in nine calcium signaling-related genes with 118 diseases of the circulatory system were explored using a large sample from the United Kingdom Biobank (N = 308,366). The clinical outcomes in electronic health records were mapped to the phecode system. Survival analyses were employed to study the role of variants in CVDs incidence and mortality. Phenome-wide association studies (PheWAS) were performed to investigate the effect of variants on cardiovascular risk factors. Results: The reported association between rs1801253 in ß1-adrenergic receptor (ADRB1) and hypertension was successfully replicated, and we additionally found the blood pressure-lowering G allele of this variant was associated with a delayed onset of hypertension and a decreased level of apolipoprotein A. The association of rs4484922 in calsequestrin 2 (CASQ2) with atrial fibrillation/flutter was identified, and this variant also displayed nominal evidence of association with QRS duration and carotid intima-medial thickness. Moreover, our results indicated suggestive associations of rs79613429 in ryanodine receptor 2 (RYR2) with precordial pain. Conclusion: Multiple novel associations established in our study highlight genetic testing as a useful method for CVDs diagnosis and prevention.

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling.

Calcium, as a second messenger, plays an important role in the pathogenesis of cardiovascular diseases (CVDs). The malfunction of calcium signaling in endothelial cells and vascular smooth muscle cells promotes hypertension. In cardiomyocytes, calcium overload induces apoptosis, leading to myocardial infarction and arrhythmias. Moreover, the calcium-calcineurin-nuclear factor of activated T cells (NFAT) pathway is essential for expressing the cardiac pro-hypertrophic gene. Heart failure is also characterized by reduced calcium transient amplitude and enhanced sarcoplasmic reticulum (SR) calcium leakage. Traditional Chinese medicine (TCM) has been used to treat CVDs for thousands of years in China. Because of its multicomponent and multitarget characteristics, TCM's unique advantages in CVD treatment are closely related to the modulation of multiple calcium handling proteins and calcium signaling pathways in different types of cells involved in distinct CVDs. Thus, we systematically review the diverse mechanisms of TCM in regulating calcium pathways to treat various types of CVDs, ranging from hypertrophic cardiomyopathy to diabetic heart disease.

Risk of Cardiovascular Disease Mortality in Relation to Depression and 14 Common Risk Factors.

BACKGROUND: Depression has been linked to a worse prognosis of Cardiovascular disease (CVD), and these two diseases share a variety of common risk factors such as unhealthy lifestyles and chronic medical conditions. However, the potential role of these common risk factors in modulating the association between depression and CVD mortality and whether the co-occurrence of depression and a specific common risk factor has a cumulative impact on CVD mortality are still largely unknown. METHODS: We pooled data from 2005-2014 of Nation health and nutritional examination survey, leading to a study population of 22,177 adults. The Patient Health Questionnaire was employed to assess the depression symptoms, and information on CVD mortality was obtained from the linked mortality file of NHANES. Fourteen common risk factors of depression and CVD were included in this study. RESULTS: Based on the interaction analyses, we found overweight was protective for the risk of CVD death in depressive participants, but not in people without depression. Moreover, relative risk-based analyses indicated a mutually promotive effect of depression and baseline CVD or living alone on CVD mortality. CONCLUSION: The novel findings in our study may facilitate risk stratification in the clinical programs targeting CVD mortality and help to shed light on the differential pathophysiological mechanisms in the depression-mediated elevation of CVD mortality.

Depression is associated with diabetes status of family members: NHANES (1999-2016).

BACKGROUND: The majority of the studies in this area focus on the psychological impact of having diabetic children or adolescents on parents, while a limited number of studies have investigated the effect of diabetes on the mental health status of family members in the general population. Thus, the aim of the current study is to explore the possible association between mental health disorders (depression, anxiety and panic) and diabetes status of family members among a national sample of adults in the United States. METHODS: Our analysis included 1,787 and 25,574 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 and 2005-2016, respectively. Diabetes status of family members was self-reported by the participants, and depression was assessed using the Composite International Diagnostic Interview (CIDI) and the Patient Health Questionnaire-9 (PHQ-9) in NHANES (1999-2004) and NHANES (2005-2016), respectively. RESULTS: With NHANES (1999-2004) participants, logistic regression indicated a marginally significant association between depression and diabetes status of family members after multivariable adjustment (P = 0.07), and trend analysis suggested that participants who had more diabetic family members were at a higher risk of depression (Ptrend < 0.01). We further validated these results using data from NHANES (2005-2016), which indicated diabetes status of family members was associated with both clinically relevant depression (PHQ-9 ≥ 10) and clinically significant depression (PHQ-9 ≥ 15) (P < 0.01). LIMITATIONS: The information about the mental health status of family members and the exact role of participants in caring for diabetic patients was inadequate. CONCLUSIONS: A positive association between depression and diabetes status of family members was observed in the general population, suggesting that psychological interventions targeting the family members of diabetic patients are worthy of attention.