This was the first population-based study that employed a large dataset from the Taiwan NHI to investigate two key parameters, the prevalence and incidence of hyperlipidemia, in patients with anxiety disorders. In order to confirm the role of anxiety disorders in the disease, we also compared these two parameters between patients with anxiety disorders and the general population.
The current study revealed that anxiety patients exhibited a 2.14-fold higher prevalence of hyperlipidemia than the general population, at 21.3% and 7.6%, respectively, in 2005. We also found that anxiety patients had a 1.64-fold higher average annual incidence of hyperlipidemia than the general population, at 5.49% and 2.50%, respectively, from 2006 to 2010. Therefore, our findings supported the hypothesis that a positive association exists between anxiety disorders and hyperlipidemia. To understand the underlying mechanism, the influence of several physiological actions needs to be taken into account. First, raising autonomic arousal in anxiety patients is mediated by the hypothalamic–pituitary–adrenal axis, which augments the release of catecholamines in the blood circulation [16]. Psychosocial threat has a negative effect on hormonal homeostasis, and also causes autonomic nervous system problems, which are all hit by the abnormal concentration of catecholamine in the circulatory system. This further causes various health problems, such as hypertension, inflammatory response, insulin resistance and other metabolic disorders [17]. One population-based cohort study revealed that women who exhibited high responses to psychological distress, such as tension, anger, and depression, at baseline had an increased risk of developing metabolic syndrome later [18]. The available evidence suggests that anxiety is connected to altered cortisol activity, and elevated levels of anxiety symptoms are linked to a less prominent cortisol awakening response [19]. Second, individuals with anxiety disorders are likely to have an unhealthy lifestyle, including unhealthy dietary habits, smoking, heavy alcohol use, sleep disturbances, physical inactivity and lack of leisure activity, which may lead to obesity, hyperlipidemia, diabetes, and hypertension [20]. One study of psychiatric outpatients in Canada revealed that lifestyle factors related to health status (hypertension, obesity, diabetes mellitus, and hyperlipidemia) and health risks are not only limited to patients with schizophrenia, but also extend to those with bipolar, depressive, and anxiety disorders [21]. Additionally, anxiety patients are associated with onset of alcohol dependence with abuse (OR, 3.2) [22], which may lead to fatty liver with hyperlipidemia. Alcohol use may lead to the development of nonalcoholic fatty liver disease due to the interaction between alcohol and metabolic disturbances. Long-term alcohol use inhibits the production of insulin or insulin-like growth factor in the liver, which causes steatohepatitis, insulin resistance, and oxidative stress or injury [23]. Third, anxiety patients have higher likelihoods of hypertension (OR, 2.61) and diabetes (OR, 1.23) [10, 11], which may produce complex interactions and are risk factors of hyperlipidemia. Fourth, anxiety patients are more likely to seek medical evaluation, therefore increasing the chance of being diagnosed with hyperlipidemia. On the other hand, the prevalence of hyperlipidemia in anxiety patients and in the general population in this NHI data study was lower than has been reported in community studies [4, 5]. Not all persons with hyperlipidemia seek medical treatment in NHI programs, and assessment for dyslipidemia is not conducted as often as assessments for diabetes and hypertension in outpatient services in Taiwan. Therefore, both physicians and psychiatrists should evaluate dyslipidemia in patients with anxiety disorders and provide comprehensive medical and psychiatric treatment. Study of subjects who had been aware of their elevated cholesterol level for a long period demonstrated that realization of their own risk of disease does lead to persisting beneficial effects on health behavior in comparison with the general population; thus, dietary counseling is recommended for the larger public to positively influence long-term awareness of hyperlipidemia [24]. Our study revealed that anxiety patients had a much higher prevalence of hyperlipidemia in the young adult age groups (age 18–39) than in the general population of the same age group (OR, 3.94). In this age group, the incidence of hyperlipidemia among patients with anxiety disorders was also noted to be much higher than that in the general population (RR, 2.24). According to the available literature, the mean age of onset of anxiety disorders is during the ages of 20–30 years.[1] Younger anxiety patients may have unhealthier lifestyles, greater alcohol use, higher smoking rates, and a higher likelihood of obesity. Younger people may also have a greater likelihood of ignoring their physical status, resulting in the underdiagnosis and undertreatment of hyperlipidemia in this age group. We should pay more attention to ensuring that young adults with anxiety disorders receive necessary lipid profile monitoring, as well as fostering a healthy diet and encouraging more regular exercise.
Considering gender, our study revealed that the prevalence of hyperlipidemia was higher in men (OR, 2.19) and in women (OR, 2.07) with anxiety disorders than in the general population. The incidence of hyperlipidemia was also higher in men (RR, 1.57) and in women (RR, 1.64) with anxiety disorders than in the general population. In addition, based on our results, the incidence of hyperlipidemia among patients with anxiety disorders was also higher in females than in males (HR, 1.1), and both genders with anxiety disorders were found to have an increased risk of hyperlipidemia. It has been reported that anxiety disorders are twice as common in women as in men [16]. Moreover, a study reported that decreasing levels of psychological distress may help women to avert development of metabolic syndrome [18]. Therefore, more attention should be paid to gender differences in anxiety patients with hyperlipidemia.
Generally, patients with anxiety disorders received antipsychotic treatment for refractory anxiety symptoms or severe insomnia. This study found that anxiety patients receiving antipsychotic medications had a higher hyperlipidemia risk than the control subjects (OR, 1.09). Antipsychotic use has been linked to weight gain, increased free fatty acids secretion in the liver, and enhanced triglyceride synthesis and very-low-density lipoprotein release in the liver [25]. Previous studies have described that some antipsychotic drugs cause individuals to become susceptible to hyperlipidemia owing to increasing weight gain, dietary changes and development of glucose intolerance [26]. A previous study also suggested that this type of drug, which is commonly prescribed, causes patients with schizophrenia or mood disorders to experience an increased risk of hyperlipidemia [27]. Therefore, in order to help patients using antipsychotic medication to detect early on the development of the disease, regular checks of blood lipid levels and proper treatment are necessary. The current study found that anxiety patients taking mood stabilizer medications had a higher risk of hyperlipidemia than the general population (OR, 1.17). Among common mood stabilizers, valproate increased the risk of metabolic disturbances owing to an increased body mass index, elevated insulin and triglycerides, and lower levels of high-density lipoprotein by affecting brain glucose transport.[28] We suggest including lipid profile testing as a routine examination in anxiety patients treated with mood stabilizers.
Diabetes and hypertension were both found to be risk factors for hyperlipidemia in the current study. Diabetes and hypertension increased the prevalence of hyperlipidemia by 3.42 and 2.15 times, respectively. Diabetes and hypertension also increased the incidence of hyperlipidemia by 1.48 and 1.73 times, respectively. Other metabolic conditions were found to be common among patients with anxiety disorder in previous studies. Anxiety patients also have increased risks of diabetes and hypertension compared to the general population [10, 11]. Patients with anxiety disorders who have multiple metabolic disturbances, including hyperlipidemia, diabetes, and hypertension, should receive a comprehensive medical evaluation and intervention.
This study used a large population-based dataset containing random samples to investigate the epidemiology of hyperlipidemia in anxiety patients and the general population. Additionally, we followed this cohort to investigate risk factors of hyperlipidemia in anxiety patients. However, there are still several limitations related to the design of this study: (1) The accuracy of diagnosis from the dataset using claims data––both the prevalence of anxiety disorders and hyperlipidemia are underestimated, and we could not link to medical charts for further justification in the present investigation. (2) No sub-classification of the disorder––subtype differentiation of anxiety disorders was not performed, such as for generalized anxiety disorder, panic disorder, phobic disorder, or obsessive-compulsive disorder, in this study. (3) Lack of detail of disorders and treatment––the comorbidities, duration, severity and psychotropic drug dosage in patients with anxiety disorders relevant to hyperlipidemia were not discussed in the current study. (4) No measures were available for certain factors–– no detailed data were available in relation to factors such as alcohol use, smoking, occupation, obesity, or other lifestyle factors that may have strong links to hyperlipidemia.