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Cardiovascular Cerebrovascular Disease

Endocrinology and Metabolism

Cerebrovascular disease, with stroke being the primary disease type, is the leading cause of long-term disability and the second leading cause of death in the world. Despite declines in cerebrovascular disease mortality rates nationally, it remains in the top 5 leading causes of death. Approximately 795,000 new or recurrent strokes occur annually in the United States, with about 600,000 being first-time events and three-quarters of all strokes occurring in people older than 65 years. On average, someone in the United States has a stroke every 40 seconds. In addition, fatal strokes occur more often in black compared with white patients. While underlying genetics can contribute to risk of stroke, most strokes are considered preventable. Clinical risk factors for stroke include older age, sex, race/ethnicity, atrial fibrillation/atrial flutter, high blood pressure, diabetes mellitus, smoking, physical inactivity, coronary heart disease, history of brain vascular malformations, and personal and family history of stroke.

Kaiser Permanente researchers have led large-scale studies in acute stroke management as well as evaluation and treatment of a variety of risk factors, including atrial fibrillation and high blood pressure. Research emphasis on prevention, risk factor management, pharmacotherapy, and acute treatment have led to improved patient outcomes. In additional, the racial, ethnic, and socioeconomic disparities in risk factors seen nationally are much less or not present among Kaiser Permanente members.

Our DOR researchers have led or collaborated on many notable studies related to epidemiology, prevention, risk factors, and acute stroke treatment, including the Kaiser Permanente Stroke EXPRESS program, Shake Rattle & Roll trial, Kaiser Permanente Stroke Trials Network, ATRIA Study and other stroke prevention studies.

Kaiser Permanente Stroke EXPRESS Program

In 2015, the American Heart Association/American Stroke Association published new clinical practice guidelines to reflect trial data showing the efficacy of endovascular stroke therapy (EST) in addition to IV thrombolysis with alteplase versus alteplase alone for patients presenting with potential acute ischemic stroke from 0 to 6 hours from last time known well. In 2019, these guidelines were updated to include new recommendations for screening patients presenting within 24 hours of the last time they were known to be well for consideration of EST.

In response to these new standards of care for acute stroke, Kaiser Permanente Northern California implemented a novel telestroke program to improve treatment and outcomes for patients with stroke. The regional program is called Kaiser Permanente Stroke EXPRESS (EXpediting the Process of Evaluating and Stopping Stroke), and it has led to higher use of IV thrombolytic therapy, shorter door-to-needle times, no increase in symptomatic intracranial hemorrhage rate, shorter length of hospital stay, and lower inpatient mortality.

Shake Rattle & Roll Trial

Blacks are more likely to experience strokes than persons from any other racial/ethnic group. Hypertension is the leading modifiable risk factor for stroke. Previous studies within Kaiser Permanente Northern California have shown a substantial improvement over the past 2 decades in blood pressure control through providing equal access to health care within our integrated health care delivery system and multipronged, system-level interventions that have made Kaiser Permanente Northern California a national leader. However, despite these efforts, blacks still have a slightly higher rate of uncontrolled blood pressure compared to whites.

Shake Rattle & Roll was funded by the National Institute of Neurological Disorders and Stroke (NINDS) as a cluster-randomized controlled pragmatic trial. It was conducted at one of Kaiser Permanente Northern California’s urban medical centers that aimed to improve hypertension control in blacks and to reduce disparities in hypertension control. The name stood for “shake” the salt habit, “rattle” the intensity of the hypertension pharmacotherapy protocol, and “roll” out the best strategies for controlling blood pressure.

Atrial Fibrillation and Stroke Prevention

Atrial fibrillation is the most common, clinically significant arrhythmia in adults, affecting up to 1 in 4 adults aged 65 years and 1 in 10 adults aged 80 years, with a projected substantial increase in the public health burden over the next several decades with the aging of populations nationally and internationally. There are more than 100,000 members in Kaiser Permanente Northern California clinically recognized to have atrial fibrillation. Atrial fibrillation is also one of the most potent risk factors for ischemic stroke, and research efforts have focused on more effective ways to accurately predict the risk of stroke and to lower the risk of ischemic stroke and systemic embolism in patients with atrial fibrillation.

The NIH-sponsored AnTicoagulation and Risk factors In Atrial Fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (ATRIA-CVRN) studies have provided key insights into risk factors for atrial fibrillation-related stroke from very large, ethnically diverse populations. These studies have generated a more accurate ATRIA stroke risk score that can be used for patient decision-making around oral anticoagulation for stroke prevention. The NHLBI-sponsored ATRIA-Chronic Kidney Disease (ATRIA CKD) cohort study involves a collaboration between Kaiser Permanente Northern and Southern California in about 180,000 members with atrial fibrillation, to determine whether stroke prevention and other treatment-related outcomes vary across the spectrum of kidney function.

Investigators at the Division of Research are also spearheading research into the links between burden of atrial fibrillation detected on continuous electrocardiographic monitoring (i.e., amount of time spent in atrial fibrillation) as an independent risk factor for stroke through the KP RHYTHM Study. They are also designing and conducting randomized controlled trials examining whether different screening strategies to detect asymptomatic atrial fibrillation followed by systematic treatment can reduce the population burden of stroke.