Health: Understanding the links between cardiovascular and psychiatric conditions
Cardiovascular diseases are the leading cause of mortality worldwide, accounting for approximately 32% of all deaths globally. Mental illnesses are similarly common, with approximately one in every eight individuals living with a mental health disorder in 2019 (World Health Organization, 2022). Given their high prevalence, these conditions are likely to exist alongside each other and this co-occurrence warrants rigorous scientific investigation.
The relationship between heart disease and mental illness is complex and bidirectional. For example, being diagnosed with heart failure can understandably cause stress and despair, and consequently elevate an individual’s risk of developing a major depressive disorder (Hare et al., 2014). Conversely, depressive disorders are known to manifest as sleep disturbances, reduced levels of physical activity and difficulty following health recommendations — all factors linked to an increased likelihood of developing cardiovascular conditions.
Evidence exists that the risks for mental and cardiovascular diseases increase in tandem (Schöttke and Giabbiconi, 2015; Ziegelstein, 2001). However, this body of work has important limitations that hinder drawing meaningful conclusions. For example, some studies only capture patient information at a single point in time, making it difficult to establish whether it was the cardiovascular or the psychiatric condition which appeared first in individuals with both illnesses (Almhdawi et al., 2021). In addition, research in this area has mainly focused on the relationship between cardiovascular health and depression or generalized anxiety disorder, with little attention paid to other psychiatric conditions such as psychosis and bipolar disorder. Lastly, no studies have so far adequately accounted for family-related mechanisms that may be driving any observed associations, such as certain genetic backgrounds or early childhood environments. Now, in eLife, Unnur Valdimarsdóttir, Qing Shen and colleagues report the results of a study designed to address some of these limitations (Shen et al., 2022).
The team (who are based in China, the United States, Iceland and Sweden) used the Swedish Patient Register to identify nearly 0.9 million individuals recently diagnosed with cardiovascular disease, and with no prior history of psychiatric disorders. Throughout the study period, these patients were then followed until they first received a mental health diagnosis within the study period. In addition, the study included a remarkable family-comparison design, whereby participants’ siblings who had no mental health or cardiovascular conditions at the time of the diagnosis were also tracked over time. The risk of developing any psychiatric condition in both patients and siblings could therefore be compared. This approach allowed Shen et al. to control for familial factors that are often difficult to measure and, if left unaccounted for in study design, could contribute to a spurious association between cardiovascular disorders and subsequent mental illness.
The results indicate that, compared to their unaffected siblings, study participants were 2.7 times more at risk of developing a psychiatric disorder within a year of having received their diagnoses of cardiovascular illness (even after accounting for familial factors, prior history of psychiatric illness and sociodemographic variables such as age, sex or socioeconomic status). Similar associations were observed when study participants were compared to non-sibling controls. In addition, individuals who developed a psychiatric disorder during that first year had a 55% increased risk of dying from a heart-related condition compared to patients who retained good mental health. In this cohort, the co-occurrence of any mental illness therefore negatively impacted the course of cardiovascular diseases.
Despite its strengths, this work also has some limitations. Notably, smoking behaviour and alcohol consumption were not adequately controlled for, despite being directly and independently associated with cardiovascular disease and mental illnesses (Dani and Harris, 2005; Mukamal, 2006). Not accounting for either of these lifestyle factors could overestimate the true relationship between these two conditions. In addition, various psychiatric subtypes with distinct phenotypes were combined — for example, all types of anxiety conditions, from generalized anxiety to post-traumatic stress disorder, were merged into a single mental health outcome. Each of these disorders is likely to have specific associations with cardiovascular health, which could not be captured by this experimental design.
The work by Shen et al. highlights how important it is to monitor psychiatric symptoms while treating cardiovascular diseases. Their findings should encourage the scientific community to fill existing knowledge gaps. In particular, it is becoming increasingly clear that evidence derived from high-income countries, where most research is conducted, cannot be directly translated to other settings. For instance, age-standardized mortality rates for cardiovascular disease are mostly decreasing in European and North American populations, while suicide mortality (as an indicator of mental health burdens) rises with age. By contrast, cardiac mortality rates are rising in certain low- and middle-income countries such as Mexico and India, with suicide mortality occurring at younger ages (Reynales-Shigematsu et al., 2018; Ke et al., 2018; World Health Organization, 2022; Phillips and Cheng, 2012). Context-specific data will therefore need to be collected for cardiovascular diseases to be appropriately managed across the world through integrated healthcare approaches.
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© 2022, Amarasekera and Jha
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Further reading
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- Epidemiology and Global Health
- Genetics and Genomics
Background:
Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.
Methods:
We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).
Results:
Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (–0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (–0.043±0.013 kg, p=0.0011) in the combined cohorts.
Conclusions:
This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
Funding:
This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background:
Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results:
Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions:
Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform.
Funding:
Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.