Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes

Klausen, Klaus; Borch‐Johnsen, Knut; Feldt‐Rasmussen, Bo; Jensen, Gorm; Clausen, Peter; Scharling, Henrik; Appleyard, Merete; Jensen, Jan Skov

doi:10.1161/01.cir.0000133312.96477.48

Cited by 601 publications

(330 citation statements)

References 39 publications

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“…209,211 These findings have been shown to apply to a broad range of populations, regardless of age, sex, ethnicity, and underlying risk factor profile, 212 and extend to very low levels of albuminuria that were previously considered innocuous (15-29 mg/d). 205,213 Collectively, these studies confirm that albuminuria is a powerful predictor of future cardiovascular events independently of eGFR, hypertension, diabetes mellitus, and traditional cardiovascular risk factors. 205,[214][215][216][217][218][219] Although albuminuria is an unequivocal risk factor for CVD in CKD, it may not be an appropriate surrogate for CKDrelated outcomes, 220 and it is even possible certain therapies that improve CKD-related outcomes may in fact increase albuminuria.…”

Section: Albuminuriamentioning

confidence: 58%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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Abstract-Patients with chronic kidney disease and end-stage renal disease are at 5-to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD.In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. P. Jousset, MD, 1 describing common causes of death among patients with Bright disease C hronic kidney disease (CKD) is an increasingly urgent public health concern that is projected to grow worldwide at a rate of 8% annually, with the fastest growth expected in developing nations.2,3 It has long been known that patients with kidney failure are predisposed to cardiovascular disease (CVD) that manifests clinically in various forms, including coronary artery disease, atrial or ventricular arrhythmias, myocardial infarction, stroke, or congestive heart failure. Over the last 30 years, it has become clear that the risk of CVD increases early in the course of progressive kidney disease and that the epidemiology, pathophysiology, prevention, and treatment of CVD and CKD are closely related and interdependent. 4 In this review, we initially describe the epidemiology of CVD among people with CKD, noting the limitations of available research. We then discuss common risk factors for CVD (traditional and nontraditional) and key shared aspects of its pathophysiology with CKD. Next we describe emerging diagnostic tools and novel therapies that may help to delay or prevent end-stage renal disease (ESRD) and to curtail the escalating burden of cardiorenal disease. In the final section, we discuss the health services and health policy challenges that CKD and its inextricably linked CVD morbidities pose worldwide, particularly for low-and middle-income countries (LMICs). Phenotypes and Epidemiology of CVD in Patients With CKDPatients with CKD and some forms of CVD share a number of risk factors and underlying pathophysiological mechanisms that, by virtue of their similarities, offer opportunities to improve their management. The epidemiology of 4 of the commonest clinical phenotypes of CVD associated with CKD is discussed below. Coronary Artery DiseaseCoronary artery disease (CAD) is a leading cause of death among people with advanced CKD. Clinical syndromes compatible with CAD (including angina and myocardial infarction) are exceedingly common in patients with nondialysis-dependent CKD, and the incidence of myocardial

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Section: Albuminuriamentioning

confidence: 58%

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

2016

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“…It is very important in the context of results of studies in general population, showing that only slightly raised levels of albumin relates to increased cardiovascular risk [40]. It was also confirmed in recent meta-analysis [41].…”

Section: Microalbuminuria In Healthy Childrenmentioning

confidence: 74%

Microalbuminuria in pediatric patients with hypertension

Varda¹

2013

Health

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Microalbuminuria in adults has been found to be an early indicator of both renal and systemic vascular disease, as well as significant cardiovascular risk predictor and therapeutic marker. Its role in essential hypertension in adults has also been well established. As diseases like hypertension and obesity have their roots in childhood and are already present in children, influencing the morbidity in adulthood, the role of microalbuminuria has been extensively investigated in children as well. Most investigations have been performed in diabetic children, confirming its clinical significance. There is also enough evidence to suggest that microalbuminuria in obese children should be taken as seriously as in children with diabetes. In children with hypertension rare studies also indicate that its presence identifies hypertensive children with higher risk, although the exact role has to be confirmed in prospective and larger studies. The mechanisms of microalbuminuria onset could be the result of renal damage secondary to hypertension or underlying renal and systemic endothelial dysfunction. Evidence from small intervention studies in children with microalbuminuria also suggests that early intervention with antihypertensive drugs is likely to be beneficial, pointing out the role of microalbuminuria as a therapeutic marker in children too. In addition, we have to stress the importance of follow-up of children with microalbuminuria, confirmation of its persistence and identification of progression. However, longitudinal prospective studies in children, investigating its future cardiovascular risk, are still lacking.

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“…18,19 Increased cardiovascular risk continues throughout the range of albumin, with no threshold, independent of diabetic status and BP. 20,21 Epidemiological studies have found a direct association between salt intake and urinary albumin. 22 Modest salt restriction lowers urinary albumin excretion even when the levels are normal.…”

Section: Discussionmentioning

confidence: 99%

Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus

Suckling

Markandu³

et al. 2016

Hypertension

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Abstract-The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. Study DesignAfter 4 weeks of participant acclimatization, participants entered into a randomized double-blind crossover study (Figure 1). Baseline measurements were taken while on participants' usual diet. Subsequently, participants were given detailed dietary advice by trained nurses to reduce salt intake to ≈5 g/d (90 mmol/d). Participants were advised not to add salt at the table or during cooking. Nurses identified food with high-salt content and advised them on low-salt alternatives. Where appropriate, the individual who prepared the food in the household was also seen. Salt-free bread was provided when required. Advice was reinforced at each visit for the duration of the study. After 2 weeks on the reduced salt diet, participants entered the randomized, double-blind crossover trial of salt versus placebo and remained on the reduced salt diet throughout the whole study. Randomization, using computer-generated random number sequences, was provided by an independent company, Healthspan Group Ltd who provided salt tablets and matching placebo tablets and had no other role in the running of the study. Participants received either 9 tablets of salt, each tablet containing 10 mmol, daily for 6 weeks or 9 matched placebo tablets, crossing over at the end of the 6-week period to take the opposite tablet for a further 6 weeks ( Figure 1). All participants and research staff were blinded to treatment allocation. MeasurementsMeasurements were performed at baseline and at the end of each 6-week study period. BP was measured by trained research nurs...

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Very Low Levels of Microalbuminuria Are Associated With Increased Risk of Coronary Heart Disease and Death Independently of Renal Function, Hypertension, and Diabetes

Cited by 601 publications

References 39 publications

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease

Microalbuminuria in pediatric patients with hypertension

Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus

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