54) after adjustment for age, gender, race, pre-existing coronary heart disease, mean arterial blood pressure, diabetes, glucose level, cholesterol level, smoking, body mass index, and geographic location within the study sites. In those with

no evidence of pre-existing heart disease, diabetes, or hypertension at enrollment to the study, the presence of retinopathy was associated with an almost threefold increased risk of future congestive heart failure (adjusted HR: 2.98; 1.50–5.94). Furthermore, the presence of retinopathy, in a nondiabetic cohort carries a similar mortality risk as diabetes itself after a cardiac event (HR: 2.28; 1.10–4.76), and over a sixfold increase in those with diabetes (HR: 6.69; 2.24–20.0) [38]. This may, in part, represent shared risk factors; however, the association remains only marginally reduced

after adjustment for known risk factors, suggesting that residual confounding is an unlikely explanation. However, click here despite these data, individuals at high risk do not get routine retinal screening [6]. There is an established ATR inhibitor co-linearity in the development and progression of microvascular and macrovascular disease [10,37,73]. This is the subject of considerable studies to establish whether there is a causal effect in either direction or simply represents shared risk factors, although it is most likely to be a complex combination of bidirectional interactions. A typical example of this would be the interplay between diabetic nephropathy, metabolic syndrome, and atherosclerosis. An elevated urinary albumin excretion rate was first described as a feature of glomerulosclerosis with a poor prognosis in 1936 by Clifford Wilson and

Paul Kimmelstiel [35]. Indeed, many textbooks still refer to diabetic nephropathy as “Kimmelstiel–Wilson” syndrome. At that time, it was thought to represent local pathology within the renal microcirculation; however, it has subsequently Erythromycin been recognized as a predictor of future cardiovascular events and mortality in diabetes, renal failure hypertension, and the general population at large [16,18,26,73,76]. Furthermore, it predicts survival after myocardial infarction [36] and stroke [59]. As such, urinary albumin excretion rate or its proxy, albumin:creatinine ratio, has become an accepted surrogate for microcirculatory target organ damage in hypertension, renal disease, and type 2 diabetes. Currently, there remains little debate as to the importance of albuminuria as a prognostic indicator, although consensus has not been reached regarding the threshold of “abnormality”, given that the association persists down into levels that are currently considered normal and below the sensitivity of commercially available assays [7]. The lack of a clear mechanistic pathway to explain the association between microalbuminuria and adverse cardiovascular outcomes has led many clinicians to believe that it is solely a marker of blood pressure exposure.