By Matthew E. Fink, MD
Synopsis: The major modifiable risk factors for cardiovascular diseases are delineated in Life’s Essential 8 (LE8), developed by the American Heart Association. These risk factors are blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration. The investigators in this analysis of two large databases in the United Kingdom and the United States demonstrated that cardiovascular health, as defined by the LE8, will also predict brain health later in life.
Source: Clicchiatti-Tuozzo S, Rivier CA, Renedo D, et al. Life’s essential 8 and poor brain health outcomes in middle-aged adults. Neurology. 2024;103(10):e209990.
A new effort is underway to focus on brain health. Traditionally, physicians have focused on treating diseases of the brain. There now is a new emphasis on identifying risk factors that cause disease, to prevent the major problems of later life that affect brain health — stroke, dementia, and depression. Stroke accounts for the largest number of disability-adjusted life years for Americans and is the second leading cause of death worldwide. Dementia, which includes Alzheimer’s disease, vascular dementia, and other dementias, is the second most serious condition in the United States causing disability-adjusted life years. Late-life depression in older adults is strongly associated with cardiovascular risk factors and is linked to cognitive impairment. It imposes a huge emotional and economic burden on patients and their families.
The American Heart Association developed a list of key risk factors for cardiovascular disease that we all can identify to improve health later in life. These have been named Life’s Essential 8 (LE8) and consist of eight modifiable cardiovascular risk factors: blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration. Substantial evidence exists that modification of these cardiovascular risk factors results in better health later in life. But there have been few clinical trials that have proven this hypothesis because the duration of such a study, and the number of patients that would be required to enroll and follow, simply is too large to contemplate.
These investigators chose to mine two large prospectively collected databases to answer these questions in an observational study. The investigators extracted data from the UK Biobank (> 500,000 Britons) and the All of Us study in the United States (400,000 participants enrolled so far), two large population studies that collected, prospectively, clinical and lifestyle information that can be analyzed and evaluated to determine the benefit of modifying the cardiovascular risk factors that are included in LE8.
A two-stage prospective study was designed using data from the UK Biobank (discovery) and the All of Us (replication). The primary exposure was the LE8 score that captured and quantified the individual elements of the LE8 and organized the data into three categories (optimal, intermediate, and poor cardiovascular health) based on LE8 scores. The primary outcome was a composite score of stroke, dementia, or late-life depression. Associations were evaluated using Cox proportional hazard models.
The discovery phase, using the UK Biobank, included 316,127 United Kingdom participants (mean age 56 years, 52% female). Over a mean follow-up time of 4.9 years, the unadjusted risk of the composite outcome was 0.7% for the optimal group, 1.2% for the intermediate group, and 1.8% for the group with poor cardiovascular health (P < 0.001). These associations remained significant after multivariate Cox models comparing the groups.
The replication stage included 68,407 participants in the All of Us study (mean age 56 years, 60% female). Over a mean follow-up of 2.9 years (standard deviation, 1.41), the unadjusted risk of the composite outcome was 2.8%, 6%, and 9.7% for the participants with optimal, intermediate, and poor cardiovascular health, respectively (P < 0.001). The replication stage analyzed the data of only five items from the LE8: blood pressure, glucose, cholesterol, body mass index, and smoking. The All of Us data did not include information regarding physical activity, diet, and sleep duration. Nevertheless, the five items included were valid indicators of overall cardiovascular health.
In a secondary analysis of the data, the strongest associations with the composite score were for smoking, sleep duration, and body mass index. In evaluating each component separately, blood pressure was the major determinant for stroke. For dementia, the most important associations were with sleep duration and physical activity. Smoking and sleep duration were most important in predicting late-life depression.
Commentary
The findings in this study are not surprising. They add to a large body of observational data that have accumulated over the years, starting with the Framingham Study in the 1960s, and showed us a pathway to good health. We have learned that good cardiovascular health leads to good brain health later in life. Therefore, we also should focus on all the lifestyle interventions that are reasonable and will result in good brain health.
Until recently, there was little emphasis on preventive medicine. In neurology, there was little understanding about the pathogenesis of many disorders, and neurologists deferred disease prevention to primary care physicians.
The shifting demographics in the United States and many other countries have resulted in a rapid growth of the population older than 65 years of age. Healthcare systems will be overwhelmed by late-life diseases unless we address this challenge now.
The LE8 includes the most important measures and risk factors for cardiovascular health that are modifiable. Active intervention and strategies to modify the LE8 can result in a significant decline in the major brain disorders of late life, and we all should try our very best to accomplish this.
Matthew E. Fink, MD, is Louis and Gertrude Feil Professor and Chair, Department of Neurology; Associate Dean for Clinical Affairs, NYP/Weill Cornell Medical College.
The major modifiable risk factors for cardiovascular diseases are delineated in Life’s Essential 8 (LE8), developed by the American Heart Association. These risk factors are blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration. The investigators in this analysis of two large databases in the United Kingdom and the United States demonstrated that cardiovascular health, as defined by the LE8, will also predict brain health later in life.
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