Insomnia Phenotypes, Cardiovascular Risk and Their Link to Brain Health

About 30% to 40% of the general population experiences insomnia symptoms of difficulty initiating or maintaining sleep, and another 10% to 15% of the general population experiences chronic insomnia disorder. The prevalence of insomnia is disproportionately higher in people with cardiometabolic risk factors, cardiovascular diseases, cerebrovascular diseases, and neurocognitive disorders, including vascular cognitive impairment. In fact, recent meta-analytic evidence from epidemiological studies has demonstrated that insomnia, especially when accompanied by objective short sleep duration, is a risk factor for incident hypertension, type 2 diabetes, heart failure, stroke, cognitive impairment, Alzheimer disease, and all-cause mortality. Insomnia should, thus, be part of the prevention and management of these adverse health outcomes. However, randomized clinical trials have not demonstrated whether treatment with cognitive-behavioral therapy for insomnia, the first-line guideline-recommended treatment, or hypnotics/sedatives improves heart- or brain-related outcomes. Studies have also failed to consider insomnia a heterogeneous disorder consisting of distinct phenotypes that result from the relative contribution of biological versus cognitive-behavioral perpetuating factors. Objective short sleep duration has emerged as a marker of physiological hyperarousal in insomnia (ie, dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activation, and increased inflammation), as a predictor of insomnia-related adverse heart and brain health outcomes and, potentially, poor response to cognitive-behavioral therapy for insomnia. This review summarizes the meta-analytic evidence on the association of insomnia with cardiometabolic risk factors, cardiovascular diseases, cerebrovascular diseases, and neurocognitive disorders, including current knowledge on the heterogeneity of the disorder. This review also summarizes the potential pathophysiologic mechanisms that lead to heart and brain morbidity, which vary across insomnia phenotypes based on objective sleep duration. This review suggests that basic and clinical sciences need to unveil the molecular, cellular, and behavioral mechanisms at play across insomnia phenotypes, as the public health and clinical implications of their association with adverse heart and brain health are demanding immediate attention.