Microalbuminuria and Peripheral Arterial Disease Are Independent Predictors of Cardiovascular and All-Cause Mortality, Especially Among Hypertensive Subjects

Abstract

Abstract-Microalbuminuria (MA) is associated with increased cardiovascular and all-cause mortality. It has been proposed that MA reflects generalized atherosclerosis and may thus predict mortality. To investigate this hypothesis, we studied the associations between, on the one hand, MA and peripheral arterial disease (PAD), a generally accepted marker of generalized atherosclerosis, and, on the other hand, cardiovascular and all-cause mortality in an age-, sex-, and glucose tolerance-stratified sample (nϭ631) of a population-based cohort aged 50 to 75 years followed prospectively for 5 years. At baseline, the albumin-to-creatinine ratio (ACR) was measured in an overnight spot urine sample; MA was defined as ACR Ͼ2.0 mg/mmol. PAD was defined as an ankle-brachial pressure index below 0.90 and/or a history of a peripheral arterial bypass or amputation. After 5 years of follow-up, 58 subjects had died (24 of cardiovascular causes). Both MA and PAD were associated with a 4-fold increase in cardiovascular mortality. After adjusting for age, sex, diabetes mellitus, hypertension, levels of total and HDL-cholesterol and triglyceride, body mass index, smoking habits, and preexistent ischemic heart disease, the relative risks (RR) (95% confidence intervals) were 3.2 (1.3 to 8.1) for MA and 2.4 (0.9 to 6.1) for PAD. When both MA and PAD were included in the multivariate analysis, the RRs were 2.9 (1.1 to 7.3) for MA and 2.0 (0.7 to 5.7) for PAD. MA and PAD were both associated with an about 2-fold increase in all-cause mortality. The RRs of all-cause mortality associated with MA and PAD were about 4 times higher among hypertensive than among normotensive subjects. We conclude that both MA and PAD are associated with an increased risk of cardiovascular mortality. MA and PAD are mutually independent risk indicators. The associations of MA and PAD with all-cause mortality are somewhat weaker. They are more pronounced in the presence of hypertension than in its absence. These data suggest that MA affects mortality risk through a mechanism different from generalized atherosclerosis. (Arterioscler Thromb Vasc Biol. 1999;19:617-624.)Key Words: microalbuminuria Ⅲ peripheral arterial disease Ⅲ mortality Ⅲ noninsulin dependent diabetes mellitus Ⅲ hypertension T he estimation of individual cardiovascular risk over and above the assessment of classic risk factors, such as age, hypercholesterolemia, and hypertension, is an important prerequisite for focusing preventive measures. It has been suggested that the presence of microalbuminuria (MA) and peripheral arterial disease (PAD) can identify subjects at especially high risk. [1][2][3][4][5][6][7][8] It is thought that the excess risk associated with MA and PAD cannot be attributed solely to an increased prevalence of conventional risk factors, such as hypertension, smoking, and noninsulin-dependent diabetes mellitus. 4,8 -13 Current hypotheses aiming to explain the association of MA and PAD with incident cardiovascular disease have focused on the possibility that both MA and PAD may b...

Microalbuminuria: do we need a new threshold?

“…14 In hypertensive subjects, albumin-to-creatinine ratios of 10-16 mg mg À1 , 2.5-to 3-fold lower than the cutoff for defining microalbuminuria, predicted increased risk of cardiovascular mortality. 7 Such a low level of albuminuria was also found to predict progression to hypertension in non-diabetic, non-hypertensive subjects, 22 and was associated with a 2.3 times greater adjusted risk of developing ischaemic heart disease. 21 In middle-aged non-hypertensive, nondiabetic Framingham Offspring Study participants, 26 those with an albumin-to-creatinine ratio of X3.9 mg mg À1 for men and X7.5 mg mg À1 for women, well below the threshold for microalbuminuria, experienced a nearly three-fold risk of cardiovascular disease ( Table 1).…”

“…[1][2][3][4][5] There is substantial evidence to indicate that UAE in the microalbuminuria range is an independent risk factor for kidney and cardiovascular disease, and of mortality in type 1 and type 2 diabetes mellitus, [1][2][3][4][5][6] hypertensive subjects, non-diabetic subjects, as well as in the general population. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] However, recent studies conducted in type 2 diabetic patients revealed that even very low UAE rates, below those conventionally accepted as the lower limit to define microalbuminuria (o30 mg per 24 h), were also associated with increased mortality. 15 Similarly, in non-diabetic subjects, albuminuria of o30 mg day À1 was found associated with older age, male gender, smoking, obesity, elevated blood pressure, left ventricular hypertrophy, dyslipidaemia, hyperinsulinaemia, salt sensitivity, lack of nocturnal BP dipping [15][16][17][18][19] and increased risk of coronary heart disease and death 10,15,[20][21][22][23][24][25] (Table 1).…”

Prevalence and risk factors for renal artery stenosis and chronic kidney disease in Japanese patients with peripheral arterial disease

“…5,6 Moreover, microalbuminuria is independently associated with increased cardiovascular risk factors and cardiovascular morbidity. 8,9 Therefore, in this study, we investigated the prevalence of RAS and clinical factors related to RAS in Japanese patients with PAD independent of hemodialysis. We also examined various risk factors for CKD based on evaluation of eGFR or urinary microalbumin (MA) in patients with PAD.…”

The Association of Poverty With the Prevalence of Albuminuria: Data From the Third National Health and Nutrition Examination Survey (NHANES III)

“…[1][2][3][4][5] In addition to the underlying primary pathological state, several factors, such as lifestyle, socioeconomic status (SES), and occupational exposures, were suggested to modify the progression and outcome of kidney diseases and may be responsible, in part, for the disproportionately high rates of end-stage renal disease in such subgroups as racial/ethnic minorities. [6][7][8][9][10] African Americans were reported to have greater rates of proteinuria.…”