Albuminuria: Prevalence,associated risk factors and relationship with cardiovascular disease

Aims/Introduction

To investigate the prevalence and associated risk factors of microalbuminuria, and to explore the relationship between albuminuria and cardiovascular disease (CVD).

Materials and Methods

A nationally representative sample of 38,203 Chinese participants was categorized by different levels of urinary albumin‐to‐creatinine ratio (ACR; 0 –10 mg/g, 10 –20 mg/g, 20 –30 mg/g, 30 –300 mg/g). The prevalence of albuminuria was compared by using a single urinary ACR cut‐off point and by sex‐specific ACR cut‐off points. Factors associated with the presence of albuminuria, and the relationship between albuminuria and CVD were analyzed by logistic regression.

Results

Prevalence of albuminuria as measured by a single ACR cut‐point was significantly lower for men compared with women (13.9% vs 19.1% in the normal glucose tolerance group; 20.8% vs 26.8% in the impaired glucose tolerance group, P < 0.01). The prevalence of albuminuria, as measured by sex‐specific ACR cut‐points, was higher for men than women (31.4% vs 29.6% in the normal glucose tolerance group; 42.2% vs 39.3% in the impaired glucose tolerance group, P < 0.01). The independent risk factors for the presence of albuminuria were aging, female sex, hypertension, hyperglycemia, obesity, dyslipidemia, insulin resistance and metabolic syndrome. The subdivided normal ACR group did not show a linear or statistically significant relationship with CVD after adjusting for conventional CVD risk factors (P > 0.05).

Conclusions

The prevalence of albuminuria was high in the general Chinese population. Aging, female sex, hypertension, hyperglycemia, dyslipidemia, insulin resistance, obesity and metabolic syndrome were all independent risk factors for albuminuria. The causal relationship between ACR and CVD might require further follow‐up investigation.     

Albuminuria and risk of nonvertebral fractures

BACKGROUND: Individuals with end-stage renal disease are at higher risk of fractures compared with subjects in the general population. We examined whether elevated albumin-creatinine ratios (ACRs) were associated with nonvertebral fractures in subjects without diabetes or macroalbuminuria. METHODS: A total of 4497 subjects (2267 men and 2230 women) 55 to 74 years old at baseline were followed for a mean of 8.4 years. Measurements of ACR, height, weight, blood pressure, lipids, serum creatinine, and bone mineral density were performed, and information about smoking and drinking habits, physical activity, prevalent diseases, and use of medication was collected before the start of follow-up. Nonvertebral fractures were registered during follow-up. RESULTS: A total of 135 men and 382 women sustained a new nonvertebral fracture. For a 1-SD higher value for the log-transformed ACR, the relative risk for a fracture was 1.01 in men (P = .94, after multiple adjustments) and 1.15 in women (P = .005). Women with ACRs in the highest quartile had a 71% higher risk of nonvertebral fractures compared with women with ACRs in the lowest quartile (P value for linear trend over the quartiles, .001). Bone mineral density tended to be lower with higher ACRs in both sexes, but this did not explain the increased fracture risk in women. CONCLUSION: Albumin-creatinine ratio was associated with nonvertebral fractures in women without diabetes or macroalbuminuria but not in men.     

Albuminuria improves R2CHA2DS2-VASc score in predicting mortality in high cardiovascular risk population

Background and aimsThe CHA₂DS₂-VASc score estimates the risk of cardioembolism in patients with atrial fibrillation (AF). It also predicts vascular events and death in different clinical settings, even in the absence of AF. The R₂CHA₂DS₂-VASc score, obtained by adding the glomerular filtration rate to CHA₂DS₂-VASc, shows a higher prediction ability for new events and all-cause mortality.The present study aims to assess whether the addition of albuminuria to R₂CHA₂DS₂-VASc score further improves its discrimination ability in predicting all-cause mortality in a sample of high cardiovascular risk population.Methods and ResultsProspective, monocentric, observational study, evaluating a subset of 737 subjects consecutively undergoing to coronary angiography at Coronary Unit of Scientific Institute “Casa Sollievo della Sofferenza” from June 2016 to December 2018.The presence of albuminuria was significantly associated with all-cause mortality (p < 0.0001). Any one-point increase of Alb-R₂CHA₂DS₂-VASc score increased mortality of about 1.5-fold (adjusted HR 1.49; 95%CI: 1.37–1.63; p < 0.0001). Considering tertiles of Alb-R₂CHA₂DS₂-VASc, the third tertile showed a 9.5-fold increased risk of mortality (HR 9.52; 95% CI: 5.15–17.60, p < 0.001).Comparing the two scores, the Alb-R₂CHA₂DS₂-VASc score (C-statistic = 0.751; 95%CI: 0.69–0.81) outperformed the R₂-CHA₂DS₂-VASc score (C-statistic = 0.736; 95%CI: 0.68–0.961) in predicting mortality (delta C-statistic = 0.015; 95%CI: 0.001–0.029). The better prediction ability of the Alb-R₂CHA₂DS₂-VASc score was also proven by an IDI of 0.024 (p < 0.0001) and a relative IDI of 24.11% (p < 0.0001), with an NRI = 0.608 (p < 0.00001).ConclusionsThe addition of albuminuria to R₂CHA₂DS₂-VASc significantly and independently predicts the risk of all-cause mortality in a sample of high CV risk patients. Moreover, Alb-R₂CHA₂DS₂-VASc outperforms R₂CHA₂DS₂-VASc.     

Aldosterone and cardiovascular risk

Through its classic effects on sodium and potassium homeostasis, aldosterone, when produced in excess, is associated with the development of hypertension and hence with higher cardiovascular and renal risk. In recent years, experimental and epidemiologic data have suggested that aldosterone also may be linked to high cardiovascular risk independently of its effects on blood pressure. Thus, aldosterone has been associated with obesity and metabolic syndrome in selected populations, and these associations may further contribute to the higher cardiovascular risk of subjects with elevated aldosterone levels. Moreover, aldosterone has been reported to promote inflammation, oxidative stress, and fibrosis in a number of tissues. Clinical evidence indicates that patients with primary hyperaldosteronism have a higher risk of developing cardiovascular and renal complications than patients with essential hypertension who have the same level of blood pressure. Aldosterone receptor blockade has been shown to lower cardiovascular mortality after myocardial infarction and in patients with congestive heart failure. Some studies have also demonstrated that aldosterone blockade could have a favorable impact on the progression of renal disease. However, prospective interventional trials are needed to further evaluate the impact of blockade of aldosterone on cardiovascular risk.     

Obesity and cardiovascular risk

Obesity has assumed epidemic proportions and is expected to decrease the life expectancy of current and future generations by its cardiovascular complications and other associated chronic diseases. Recognizing the gravity of this trend, the American Heart Association recently identified obesity as an independent and important modifiable risk factor for cardiovascular disease. Obesity is known to cluster with other cardiovascular and metabolic risk factors constituting the cardiometabolic syndrome. The pathophysiogic link between obesity and cardiovascular disease is complex and involves multiple metabolic and inflammatory risk factors. In an attempt to better elucidate this major public health problem, this article reviews obesity as an epidemic, the structural and functional changes in the cardiovascular system as a result of obesity, and the pathophysiology of obesity-related cardiomyopathy. The sheer magnitude of the problem of obesity with its immense cardiovascular consequences warrants immediate intervention.     

Chemokines and cardiovascular risk

Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin- 8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease.     

Hyperglycaemia and cardiovascular risk

Cardiovascular diseases represent, today, the principal cause of mortality in the general population, especially in subjects with type 2 diabetes mellitus. In these patients the risk of death from cardiovascular diseases is equal to that of non-diabetic subjects with a previous episode of myocardial infarction. Many factors concur to determine such high risk. Hyperglycaemia contributes to the increase in morbidity and cardiovascular mortality associated with diabetes mellitus. Hyperglycaemia acts as a multiplier of cardiovascular risk due to frequent association of multiple risk factors in diabetic patients. Therefore, effective treatment requires a more complete assessment of quantitative and qualitative aspects of glycemic control as well as all components of the diabetic syndrome or, more commonly, metabolic syndrome.     

Testosterone and cardiovascular risk

Cardiovascular (CV) disease is one of the most common causes of death in the western populations and, nowadays, its incidence is increasing even in the developing countries; although CV disease affects both sexes, it is more frequent in males in whom it shortens the average life expectancy. In this regard, this difference has been wrongly attributed for many years to the negative effects of testosterone (T); however, nowadays, a large amount of evidence suggests that this hormone may have protective effects on the CV system and that, indeed, the low levels of T could be associated with an increased CV risk and with an augmentation of morbidity and mortality in males. Such an aspect gains great relevance in light of the consideration that T decrease, besides occurring as a consequence of rare pathological conditions, can often take place with natural aging, causing a state of “male menopause”, also called late-onset hypogonadism. In this review, we aimed to summarize the present state of the art concerning the association between T deficit and CV disease by analyzing the protective role of T on CV system and the relationship of this hormonal lack with metabolic syndrome, CV morbidity and mortality, and with the CV complications, such as ischemic heart disease, heart failure and stroke, that frequently occur in T deficiency.     

Glucose and cardiovascular risk

The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages between normal glucose homeostasis and diabetes, based on fasting and challenged glucose levels, respectively. Criteria were established for 'the metabolic syndrome', as a cluster of cardiovascular risk factors that frequently coincides with the abnormal glucose tolerance state. The extent to which the glucose level itself should be regarded as a cardiovascular risk factor is the subject of ongoing debate. Recent research suggests that cardiovascular risk is related to the plasma glucose level even in the normal range of glucose concentrations. The impact of glucose in relation to cardiovascular events is discussed in this review.     

Microalbuminuria and cardiovascular risk

Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal.     

Rosiglitazone and cardiovascular risk

A meta-analysis of 42 clinical trials suggested that rosiglitazone, a widely used thiazolidinedione, was associated with a 43% greater risk of myocardial infarction (P = 0.03) and a 64% greater risk of cardiovascular death (P = 0.06). However, a number of criticisms have been raised that potentially undermine the conclusions of this analysis. In this article, we point out some of these limitations, summarize the currently available evidence concerning rosiglitazone and cardiovascular risk, share implications for drug safety evaluation, and offer practical recommendations to health care providers. We conclude that the data showing the increased risk for myocardial infarction and death from cardiovascular disease for diabetic patients taking rosiglitazone are inconclusive.     

Albuminuria and VEGF as early markers of cardiovascular disturbances in young type 1 diabetic patients

AimsThe aim of the study was to assess myocardial perfusion by means of non-invasive diagnostic methods and measurement of the plasma concentration of vascular endothelial growth factor (VEGF) in patients with long-lasting type 1 diabetes.Methods and resultsThe study was performed on 41 Type 1 diabetic patients (23 females, 18 males), aged 30 ± 7.6 with a duration of disease 15.2 ± 5.5 years. 17 patients exhibited microalbuminuria (10 females, 7 males) and 24 subjects were without microalbuminuria (13 females, 11 males). The methods used included a 24-h ECG tape, an exercise treadmill test, echocardiological evaluation with dobutamine and atropine challenge and single photon emission computer tomography (SPECT) at rest, and after dipyridamol induction of ischemia. All the exercise and stress echocardiography tests were negative. There were significant differences between microalbuminuric and normoalbuminuric subjects in the duration of their exercise tests (586.9 ± 110.5 vs. 664.9 ± 133.2 s, p = 0.027), performed work (11.4 ± 1.6.vs. 12.6 ± 1.8 METs, p = 0.045), achieved pulse limit (89.1 ± 3.6 vs. 92.6 ± 5.2%, p = 0.037), rest ejection fraction (55.8 ± 8.7 vs. 62.0 ± 4.4%, p = 0.040), abnormal changes in SPECT (53 vs. 21%, p = 0.047) and VEGF concentration (101.5 ± 7.8 vs. 75.15 ± 16.5 pg/ml, p < 0.05). The presence of retinopathy increased 12-fold the probability of significant changes in the SPECT (OR 12.1, 95% CI 1.38–105.64, p = 0.02) and nephropathy (OR 4.27; 95%CI 1.09–16.83, p = 0.03).ConclusionAsymptomatic patients with long lasting type 1 diabetes may have disturbances in myocardial perfusion, especially these with microalbuminuria.