Participants who met the inclusion and exclusion criteria were divided into four groups (hypertensive, diabetic, hypertensive diabetic and normotensive non-diabetic).

The inclusion criteria for patients with hypertension and/or type 2 DM were: age ≥18 years, with hypertension (blood pressure [BP] ≥140/90 mmHg or under antihypertensive therapy) and/or diagnosed DM (fasting blood glucose ≥126 mg/dl or 2-hour glucose level ≥200 mg/dl or under oral antidiabetics [OADs] and/or insulin) and laboratory test results in the previous 12 months. Pregnant, menstruating or breastfeeding women were excluded, as were patients monitored regularly in nephrology consultations, those with febrile disease or concomitant urinary tract infection, type 1 DM, autoimmune disease or receiving treatment with oxytetracycline, and those participating in vigorous physical activity in the previous 24 hours, all of which increase the likelihood of a false positive result for MAU.

Inclusion criteria for the control group were: age ≥18 years, BP<140/90 mmHg, fasting blood glucose <110 mg/dl and not taking antihypertensive medication or OADs or insulin.

RACE was a multicenter, descriptive, observational, cross-sectional epidemiological study. Recruitment took place between October 2010 and January 2011 and 469 general practitioners (GPs) participated (145 from the North region, 150 from the Central region, 101 from the Lisbon region, 36 from the Alentejo, 17 from the Algarve, 7 from Madeira and 13 from the Azores).

In order to minimize selection bias, each GP recorded the inclusion and exclusion criteria of the first four patients seen each day until 20 participants fulfilled the inclusion criteria of the respective groups – 15 with hypertension and/or DM and five normotensive non-diabetic controls – and did not present any exclusion criteria. Those not fulfilling all the criteria were considered ineligible.

In order to ensure the consistency of the results, all PHCs screened for MAU using Micral® test strips, which have a sensitivity of over 80%,19,20 following a standard procedure for sample collection and testing. The levels of MAU considered in the analysis were <20 mg/l (negative result), ≥20 mg/l to <50 mg/l, ≥50 mg/l to <100 mg/l and ≥100 mg/dl. The results were entered in the patients’ records and data were collected on the following variables: demographic (age, gender, weight, height, body mass index [BMI], smoking and physical activity); comorbidities (dyslipidemia, stroke or transient ischemic attack [TIA], peripheral vascular disease [PVD], coronary artery disease [CAD], left ventricular hypertrophy [LVH], heart failure [HF] or other); and cardiovascular medication (lipid-lowering drugs, antihypertensives, digoxin, antiarrhythmics and antianginals); anticoagulants, antiplatelets, and OADs or insulin. Two BP measurements were taken at least 1 min apart, following standard procedures. The following laboratory test results were also recorded if assessed at least once in the previous 12 months: fasting blood glucose, glycated hemoglobin (HbA1c), serum creatinine, total cholesterol, high-density and low-density lipoprotein (LDL) cholesterol and triglycerides.

The sample size was calculated based on estimates for the four patient groups under study (hypertensives, diabetics, hypertensive diabetics and controls). Estimates of the prevalence of MAU range between 4% and 46%; the higher value was used to determine the sample size. With a sample error of 5% (for a 95% confidence interval), 382 individuals per patient subgroup from each of the seven regions (five NUTS II regions plus two autonomous regions) would be required. Each region would thus include 1528 participants, a total of 9168; on the assumption that 10% would be ineligible, the overall size of the sample would be 10085 participants.

Descriptive statistics were used to analyze all the data collected. Means, medians and standard deviations were determined for quantitative variables, and absolute and relative frequencies for qualitative variables. All estimates were accompanied by 95% confidence intervals. The normality of distribution of the quantitative variables was assessed using the Kolmogorov-Smirnov test, bivariate tests (t tests, ANOVA, chi-square test) and multivariate analyses in accordance with the study objectives. Independent factors associated with MAU were obtained using a stepwise logistic regression model (Wald test) (p<0.05 for entry and p>0.10 for exit). The level of significance for all analyses was 0.05 (two-tailed).

During the three and a half months of the study a total of 11288 participants were recruited, of whom 1641 (14.5%) were ineligible. The final study population included 9198 individuals, of whom 41% were hypertensive (n=3769), 33.7% hypertensive diabetic (n=3100) and 4.6% normotensive diabetic (n=423), the remaining 20.7% constituting the control group (normotensive non-diabetic; n=1906) (Table 1 and Figure 1).

Figure 1.

Percentage distribution and age and gender distribution of the four subgroups. DM: diabetic; F: female; HT: hypertensive; NT: normotensive.

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Overall, there was a slight predominance of women (54.7%), which was significantly higher in the control and hypertensive groups. The normotensive diabetic group was the only one in which the gender distribution did not differ significantly from the general Portuguese population (Table 2). Mean and median ages of the four subgroups are shown in Table 3 and Figure 2. Median age differed significantly in all subgroups (p<0.001); the hypertensive diabetic group was significantly older (mean age 65±11.1 years), followed by the hypertensive group (mean age 63.4±12.9 years), the normotensive diabetic group (mean age 59±12.2 years) and the control group (mean age 46.6±15.4 years).

Figure 2.

Age ranges of the four subgroups.

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Most hypertensives were uncontrolled (only 34% had BP<140/90 mmHg), although BP control was better in the hypertensive diabetic group (63.7% had BP<140/90 mmHg). More than a third of participants were obese; the percentage of obese individuals was higher among hypertensive diabetics (only 59% had BMI<30 kg/m2). Blood glucose control was also poor (HbA1c<7% in 32–33% of diabetics). Overall, dyslipidemia was present in 73% of the hypertensive diabetic group, 62.5% of non-diabetic hypertensives, and 51% of normotensive diabetics. More than 60% of the study population had LDL-cholesterol <130 mg/dl. However, with regard to the risk profile of the study population, LDL-cholesterol <100 mg/dl was observed in only 25% of hypertensives, 31% of normotensive diabetics and 34% of hypertensive diabetics. There was a tendency for favorable triglyceride values (<150 mg/dl) in these populations, although this was less common among hypertensive diabetics (Figure 3). Smoking was more common in the control group (16%), and less common in the remaining subgroups (11% in normotensive diabetics, 10% in hypertensives and 9.3% in hypertensive diabetics).

BMI: body mass index; HbA1c: glycated hemoglobin; LDL-C: low-density lipoprotein cholesterol; TG: triglycerides.'> BMI: body mass index; HbA1c: glycated hemoglobin; LDL-C: low-density lipoprotein cholesterol; TG: triglycerides.' title='Risk factors and laboratory parameters by subgroup. BP: blood pressure; BMI: body mass index; HbA1c: glycated hemoglobin; LDL-C: low-density lipoprotein cholesterol; TG: triglycerides.'/>

Figure 3.

Risk factors and laboratory parameters by subgroup. BP: blood pressure; BMI: body mass index; HbA1c: glycated hemoglobin; LDL-C: low-density lipoprotein cholesterol; TG: triglycerides.

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Figure 4 shows comorbidities by subgroup. Previous stroke/TIA was rare in the control group and highest (8.3%) in the hypertensive diabetic group. PVD and CAD were also infrequent in the control group; PVD prevalence was 14.7% in hypertensive diabetics, 9% in hypertensives and 5.4% in normotensive diabetics, while CAD prevalence was highest in hypertensive diabetics (12.3%).

TIA: transient ischemic attack.'> TIA: transient ischemic attack.' title='Comorbidities in the four subgroups. TIA: transient ischemic attack.'/>

Figure 4.

Comorbidities in the four subgroups. TIA: transient ischemic attack.

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Only 1% of controls and 1.4% of normotensive diabetics had LVH; this figure rose to 9.9% in hypertensives and 14.4% in hypertensive diabetics, giving an overall prevalence in hypertensives of 11.9%. A history of HF was observed in 9.4% of hypertensive diabetics, with much lower percentages in non-diabetic hypertensives (4.9%) and normotensive diabetics (0.2%).

Lastly, with regard to chronic renal failure (CRF), 17.8% of diabetic and non-diabetic hypertensives had stage 3 CRF, with estimated glomerular filtration rate (GFR) of <60 ml/min/1.73 m2.

Based on risk factors, with poor BP and blood glucose control, and cardiovascular comorbidities, the population presented a high global cardiovascular risk profile. According to the 2012 and 2013 European guidelines on cardiovascular risk,11,21 of the 8823 patients analyzed (risk assessment was not possible in 375) 22.3% were at very high risk and 39.6% at high risk (a total of 61.9%), while 18% were at intermediate risk and 20.2% at low risk.

Most patients were taking cardiovascular medication, mainly lipid-lowering drugs (50.5% of hypertensives and 64.9% of diabetic hypertensives, as well as 40.4% of normotensive diabetics and 19.7% of controls) and antihypertensives (particularly renin-angiotensin system [RAS] inhibitors, prescribed in 84.8% of hypertensives: 37.5% with angiotensin-converting enzyme inhibitors, 54.3% with angiotensin receptor blockers and 8.2% with direct renin inhibitors) (Figure 5A and5B). Of the total of hypertensives, diabetic and non-diabetic (n=6869), 11.3% were taking no antihypertensive medication. Of the remaining 88.7%, 30% were taking one antihypertensive (of whom 54.6% had uncontrolled BP), 46% were taking two and 24% more than two. Use of OADs or insulin in hypertensive and normotensive diabetics is shown in Figure 6; there were no significant differences in prescription patterns between these two groups.

Figure 5.

(A) Percentage of patients medicated with lipid-lowering drugs, diuretics and inhibitors of the renin-angiotensin system by subgroup. ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin II receptor blockers; DRIs: direct renin inhibitors. (B) Percentage of non-diabetic and diabetic hypertensives medicated with other antihypertensives by subgroup. CCBs: calcium channel blockers.

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Figure 6.

Percentage of normotensive and hypertensive diabetic patients prescribed oral antidiabetics or insulin. DPP-4: dipeptidyl peptidase-4.

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Figure 7A shows the prevalence of MAU in the different subgroups. The highest prevalence (58%) was observed among hypertensive diabetics, closely followed by normotensive diabetics (51%). The prevalence among non-diabetic hypertensives was 43% and 49.3% of all hypertensives, markedly higher than the 12% observed among controls. The differences between groups were significant (chi-square: p<0.001). Figure 7B presents the percentage distribution of MAU values as assessed by urine strip testing, showing that 42.5% of non-diabetic hypertensives had a positive test, lower than in normotensive diabetics (51.4%) and hypertensive diabetics (57.6%), while 20.6% of controls had a positive MAU test.

Figure 7.

(A) Prevalence of microalbuminuria in the four subgroups. (B) Percentage distribution of microalbuminuria values on urine strip testing in the four subgroups.

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Logistic regression analysis showed that the following factors were associated with a positive MAU test: DM (odds ratio [OR] 3.675; p<0.001), hypertension (OR 2.350; p<0.001) and, interestingly, hypertension treated by calcium channel blockers (CCBs) (OR 1.261; p=0.039) or antiplatelets (OR 1.391; p=0.001), as well as age, male gender, HbA1c, total cholesterol and systolic BP (Table 4).

The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).

The authors declare that they have followed the protocols of their work center on the publication of patient data.

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.