Young adults who feel depressed are more likely to develop cardiovascular disease (CVD)


Depression is a nontraditional risk factor for cardiovascular disease (CVD).

In this cross‐sectional analysis of a nationally representative sample of young adults, depression and PMHDs were independently associated with CVD, with no significant interaction by sex or urban/rural status. In addition, among people with no CVD, depression and PMHDs were independently associated with suboptimal CVH, with a dose‐response relationship.

Self‐report of depression was highly prevalent in our study, with ≈1 in 5 young adults reporting depression, 2‐fold higher than the national prevalence of at least 1 major depressive disorder of 8.4% in all US adults in 202024 but similar to recent prevalence estimates in young US adults.24, 25

Furthermore, during the COVID‐19 pandemic, the percentage of US adults who experienced depression or anxiety jumped from 36.4% to 41.5%, with the highest spike among people aged 18 to 29 years, according to Centers for Disease Control and Prevention data,26 highlighting the need to develop targeted interventions to address the burden of poor mental health in young adults to reduce the depression‐associated health risks.27

Our finding of higher odds of CVD in participants with depression is consistent with prior studies in other geographic locations. In a pooled cohort from >30 countries, Harshfield et al found baseline depression symptoms to be associated with incidence of CVD among an older population (mean age, 63±9 years).13 In a multicenter study focusing on low‐ and middle‐income countries, having ≥4 depressive symptoms in patients without a history of CVD was associated with 14% increased risk of incident CVD and all‐cause mortality.14

A recent study among individuals of European ancestry showed depression frequency was associated with incident coronary artery disease, type 2 diabetes, and atrial fibrillation.28

In the United States, a smaller single‐center study of 882 participants found moderate to severe depression to be associated with low (worse) CVH score,29 whereas similar findings were reported in moderate sized population‐based studies.30, 31 Our study explores the association of depression and PMHDs, which represent recent and active mental health conditions, with CVD in a larger population of US young adults, with subanalyses by sex and urban/rural status; it also assesses the association of depression and PMHDs, with suboptimal CVH, in people without CVD.

The relationship between CVD and depression has been regarded as bidirectional. There is evidence that depression is an independent risk factor for CVD.12, 13, 32 The increased odds of CVD in people with depression may stem from the unhealthy lifestyle that may be associated with depression, such as sedentary behavior,33, 34 unhealthy eating,35, 36 and smoking.37, 38, 39

There are multiple physiological pathways, such as abnormalities in glucose and lipid homeostasis and coagulation cascade abnormalities related to chronic stress, by which psychological health and well‐being may influence CVH and CVD risk.40, 41, 42 Other possible mechanisms that may explain the association of depression with CVD include the neurohormonal imbalances and overactivation of the sympathoadrenal and hypothalamic‐pituitary‐adrenal axis that have been demonstrated among people with depression.12, 43

It is important to recognize that CVD can also lead to depression. Indeed, several studies have reported higher rates of depression among people with CVD.44, 45, 46, 47 A rate of 15% of major depressive disorder has been reported in patients after myocardial infarction or coronary artery bypass grafting,44 and this rate is >20% in patients with heart failure and is much higher in advanced heart failure.45

In another study, poststroke depression was seen in 5% of patients within 3 years after ischemic stroke diagnosis, and a higher 3‐year mortality was observed in patients with poststroke depression.48

Our findings showed no sex differences in the association of depression with CVD, contrary to the findings of some prior studies in which stronger associations between depression and incident CVD, CVD mortality, and all‐cause mortality were found in men.49, 50

Men tend to underreport poor mental health and are also less likely to seek treatment,51, 52, 53 which may contribute to the apparent increase in risk.

Other studies have also shown stronger association of depression and incident coronary artery disease among women,28 demonstrating that sex differences in this association are highly heterogeneous across the literature.

Studies on urbanization and risk of depression have been inconsistent in different geographic locations. Although some studies suggest an increased risk of depression in individuals residing in urban areas, some have found a protective or a null association.18, 54, 55 Evidence from a meta‐analysis showed higher odds of depression in urban areas compared with rural areas in developed countries, with a pooled OR of 1.44.18

Factors, such as unhealthy diets, reduced physical activity, stress, unsafe neighborhoods and isolation, lack of social support, and lack of green spaces, in urban areas may be contributory.19, 56 In this study, however, the association of mental health and CVD did not vary by urban/rural status.

Last, studies have found that depression, stress, and anxiety, attributable to disparities in social determinants of health, adverse childhood experiences, general trauma, and structural racism, could place certain populations and racial and ethnic underrepresented groups at a higher risk of CVD and poor mental health.57, 58

Future research should focus on addressing the role of social determinants of health and health disparities in improving the intersection between mental health and health outcomes.

Our findings have several important clinical and public health implications. Our study highlights the need for clinicians to recognize the risk of CVD in patients with depression and poor mental health. Given the increased odds of CVD among patients with depression, it may be necessary to enhance screening for depression and evaluation of mental health in general, as an additional screening tool in evaluating CVH and monitoring for CVD.

Among people without a clinical diagnosis of depression, a unique group that is likely captured by our assessment of PMHDs, improvement in their mental health may likely be beneficial for CVD prevention. At least, Screening of individuals who have had a major cardiovascular event for mental health conditions and emotional and psychological well‐being, and communicating with close family members and friends, can prove to be beneficial. Mental health screening among those with established CVD may be important to optimize secondary prevention.

Targeted interventions that improve mental health and reduce mood disorders may be necessary in reducing CVD and improving overall CVH. Cardiac rehabilitation programs often incorporate stress reduction and mindfulness, but mental health could be more strongly integrated, particularly for those with mental health conditions. Interventions to address mood disorders in young adults should consider targeting CVH, such as physical activity,59 weight management, and smoking cessation.

Although lifestyle changes may be particularly challenging in patients with depression, a multidisciplinary approach and collaborative and integrated care between health care professionals, such as mental health physicians, psychologists, psychiatrists, nutritionists and addiction specialists, primary care physicians, and cardiologists, may be needed to better improve mental health and reduce CVD risk.

Future research should focus on incorporating a validated screening tool in the Life’s Essential 8 metrics for appropriate screening and interventions in a patient‐centered approach. Last, these data are reflective of the pre–COVID‐19 world, and future studies are encouraged to explore these associations in the post–COVID‐19 period.

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COVID-19 and depression in general population and in women

Depression is a psychiatric condition characterized by alterations in regulators of mood, behavior and affection and represents one of the most common causes of disability in high-income countries, being associated with high societal and healthcare costs, both in terms of direct medical expenses and reduced work productivity associated with functional impairment.

It is more prevalent in women than men, with a doubled worldwide chance of suffering from depression, especially during the mid-puberty and later life.

About 20-25% of women go through depression during their life and depression symptoms have been considered a relevant emergent non-traditional risk factors for CVD in the female population. Moreover, patients with CVD suffer from depression more than the general population and people with depression are more prone to develop CVD, as they commonly adopt habits that overlap with CV risk factors. [4]

A growing body of evidence is emerging about the effects of COVID-19 pandemic on mental health in the general population, resulting in identification of a number of clinical and demographical factors that predict the risk of depression. A meta-analysis of community-based studies about the prevalence of depression during COVID-19 pandemic, including a total of 12 studies, highlighted a pooled prevalence of depression of 25% (95% CI: 18%-33%), with significant heterogeneity between studies. [5]

Moreover, symptoms of depressive disorder increased considerably in the United States during April–June of 2020, compared with the same period in 2019. [6]

Female gender firstly emerged as a significant risk for worsening health status and higher self-reported depression symptoms, as women seem to have both a higher prevalence of risk factors known to intensify during a pandemic, including preexisting depressive and anxiety disorder, chronic environmental strain and domestic violence.

Moreover, they experience pandemic-related stressors specific to reproductive functioning and stages, i.e. fertility issues, pregnancy, miscarriage, postpartum depression, intimate partner violence. [3]

A recent survey study by Perlis et al., including a total of 3904 individuals, investigated whether acute COVID-19 symptoms are associated with the probability of subsequent depressive symptoms. 52.4% of patients met criteria for moderate or greater symptoms of major depression; at the regression analysis, these symptoms were more likely among younger individuals, men and among those with greater self-reported overall COVID-19 severity. [7]

In particular, female gender, younger age, student and unemployment status, specific physical symptoms (i.e., myalgia, dizziness), and poor self-rated health status were firstly significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression. [8] Analogous data were described for the female health care workers. [9]

Besides the short-term interaction between COVID-19 and depression, a considerable risk for psychiatric and neurological morbidity in the 6 months after COVID-19 infection exists, especially in patients who had severe COVID-19. [10,11]

Moreover, psychiatric morbidity at follow-up appears to be associated with persistent physical symptoms such as breathlessness and myalgia, the latter being associated with impaired quality of life, both in adults and young people. [12]

Middle aged women, under the age of 50, seem to have a greater chance of suffering a variety of devastating ongoing symptoms, due to the presence of a persistent inflammatory burden, such as fatigue, breathlessness, muscle pain, anxiety, depression, and “brain fog” after hospital treatment for COVID-19 (Table 1 ). [13]

Table 1

Relevant clinical trials that explored the epidemiology of depression and mental health issues in COVID-19 and long COVID syndrome.

ReferencesTotal pts (n), % women (%)PopulationAimResults
Perlis R. et al. [7]3904 (44.3%)US adult participants in 8 waves of an internet-based nonprobability survey conducted by Qualtrics with multiple panels of respondentsAssociation between acute COVID-19 symptoms and the probability of subsequent depressive symptoms.52.4% of participants met the criteria for symptoms of major depressive disorder. Presence of headache was associated with greater probability of moderate or greater depression symptoms (adjusted odds ratio [OR], 1.33; 95%CI, 1.10-1.62). Women were less likely to have symptoms than men (adjusted OR, 0.72; 95%CI, 0.61-0.84).
Taquet M. et al. [10]236 379 (55.6%)Retrospective cohort study from the TriNetX electronic health records networkIncidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis.The estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33.62% (95% CI 33.17–34.07); the incidence of mood disorder was 13.66% (13.35-13.99%) in the whole population and increased in patients with hospitalization and with intensive therapy unit admission.
Huang C. et al. [11]1733 (48%)Patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020Describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors.Anxiety or depression was reported among 23% (367 of 1617) of patients.
Naidu SB. et al [12]946 (39.8%)Adults discharged from hospital with a clinical diagnosis of COVID-19Evaluation of the mental health burden in adults discharged from hospital with COVID-19 and exploration of the factors that contribute to this.13.8% of adults screened was positive for depression. Adults with positive PHQ-2 and TSQ were significantly more likely to experience persistent symptoms (PHQ2 80.0% vs. 41.8%, TSQ 88.8% vs. 42.9%; both p<0.001) and they were also less likely to have returned to work (PHQ2 36.0% vs. 57.6%, p=0.004; TSQ 37.5% vs. 56.5%, p=0.01).
Torjesen I. [13]1077 (36%)Adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months laterImpact of COVID-19 on health and employment, to identify factors associated with recovery and to describe recovery phenotypes.At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health- related change in occupation. Factors associated with failure to recover were female, middle- age, white ethnicity, two or more co-morbidities, and more severe acute illness.

List of abbreviations: CVD, cardiovascular disease; Pts, patients; OR, odds ratio; AE, adverse events; DM, diabetes mellitus; PhA, physical activity; AMI, acute myocardial infarction; PHQ-9, Patient Health Questionnaire-9; CAG, coronary angiography; AF, atrial fibrillation; MSIMI, mental stress-induced myocardial.

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