Low grade albuminuria as a risk factor for subtypes of stroke - the HUNT Study in Norway

Abstract

Background and purpose Albuminuria is a marker for endothelial dysfunction and knowledge on its association with stroke and stroke subtypes are limited. Methods Corresponding data from 7261 participants of the population-based HUNT2 study (1995–1997) was linked with hospital records, identified all patients registered and diagnosed with a first-time stroke. Each diagnosis was validated by reviewal of the medical record appertaining to the individual. We then applied Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between albuminuria (measured as albumin-to-creatinine-ratio, ACR) and diagnosis of stroke and stroke subtypes. Results 703 (9.7%) participants developed a first ischemic stroke during a median follow-up of 15 years. Higher albuminuria was associated with a higher rate for ischemic stroke and the risk rose steadily with increasing ACR (15% increment per unit increase in ACR concentration in mg/mmol). In the fully adjusted model, the HR for all ischemic strokes was 1.56 (95% CI 1.24–1.95) for those with an ACR ≥3 mg/mmol compared to participants with an ACR < 1 mg/mmol. Overall, increasing ACR was associated with a higher risk of all ischemic stroke subtypes. This was seen to be strongest for lacunar stroke (HR 1.75, CI 1.12–2.72, p = 0.019), and also for stroke of undetermined etiology (HR 1.53, CI 1.11–2.11, p = 0.009) and those caused by atherosclerosis in the large arteries (HR 1.51, CI 0.78–2.94, p = 0.186) than for cardio-embolic stroke (HR 1.22, CI 0.64–2.3, p = 0.518). Conclusions Albuminuria is an important risk factor, potentially already at low grade, for ischemic stroke especially for lacunar subtype. Measuring albuminuria is both cheap and readily available. This offers the opportunity to evaluate the risk for endothelial dysfunction and thus the subsequent risk for stroke and cerebral small vessel disease.

Association Between Levels of Depression Symptoms and Moderately Increased Levels of the Inflammation Marker Albuminuria Is Explained by Age and Comorbidity.

“…The cerebral small vessel disease, de ned as a disease of the small blood vessels in the brain, and a frequent cause of stroke and dementia, is also hypothesized to lead to depression (the vascular depression hypothesis) through disruption of neuronal circuits involved in mood regulation 28,29 . Although we recently published the results of a positive association between vascular dementia and lowgrade albuminuria 30 and have found signi cant association between lacunar stroke and albuminuria 31 in the same HUNT-material, we could not support the vascular depression hypothesis by our results. However, the results may re ect the limitation of HADS in measurement of depression more than the true association between depression and vascular endothelial dysfunction.…”

Urine Protein Levels Predict Future Development of Cerebral Infarction in Koreans

“… 11 12 13 Although many advances have been made in identifying risk factors for multiple subtypes of stroke, including stroke due to macrovascular disease and cardiac embolic stroke, and understanding the pathophysiology of stroke, knowledge about the causes of lacunar stroke is limited. 14 Several studies have shown that blood-brain barrier dysfunction is an important part of cerebral small vessel diseases. Endothelial dysfunction may be the fundamental step in the deteriorating of lacunar infarction.…”

Low-Grade Albuminuria and Its Relationship with Cardiovascular Disease Risk in Hypertensive and Diabetic Patients in Primary Health Care

“…There is evidence suggesting that LGA, below the microalbuminuria threshold, is associated with increased prevalence of metabolic syndrome and its components 15 , systemic vascular dysfunction and cardiovascular mortality 22 . LGA is prevalent in patients presenting hypertension and is associated with an unfavorable outcome 22 , IT may identify individuals who are more likely to develop AH 6 , it may also be used to detect early cardiovascular disease in patients presenting DM type 2 20 , it may contribute to the risk of carotid atherosclerosis 23 , and it may also be used to independently predict the incidence of cardiovascular disease and mortality in apparently healthy individuals with optimal blood pressure and without diabetes and in the general population 24 . LGA has also been associated with left ventricular hypertrophy and left ventricular diastolic dysfunction in hypertensive patients 7 and is potentially an important risk factor for ischemic stroke, especially for the lacunar subtype 14 .…”