I. Vukovic

[OP.2B.03] GLOMERULAR HYPERFILTRATION AS A RISK FACTOR FOR RENAL IMPAIRMENT AND HYPERTENSION IN APPARENTLY HEALTHY SUBJECTS.

Objective: Chronic kidney disease(CKD) is established CV risk factor, and already early renal impairment(RI) increases risk for hypertension(HT) and loss of renal function. It was reported that blood pressure (BP) and metabolic derangements are associated with glomerular hyperfiltration(GHF), and GHF increases risk of developing microalbuminuria (MA) in HT stage 1. Our aim was to analyze whether GHF predicts progression to HT and RI in apparently healthy subjects. Design and method: Out of 954 subjects enrolled in ENAH follow-up study, 371 (137 m, 234 w; mean age = 46 years) were eligible for further analysis:100 with optimal, 72 with normal BP, 70 with PHT (high normal BP), and 129 with newly diagnosed untreated HT. Follow-up period was 77 ± 12 months. Exclusion criteria were treatment with antihypertensive drugs, diabetes, pregnancy, eGFR<60 ml/min, CV or cerebrovascular incident, chronic terminal diseases, dementia, immobility and missing data. BP and heart rate were measured using Omron 6 device following the ESH guidelines. Uric acid, glucose, lipids, serum creatinine, hsCRP, leptin and adiponektin were determined; HOMA index was used to calculate insulin resistance and MDRD formula to estimate GFR. Albumin to creatinine ratio (ACR) was determined from the first morning spot urine. GHF was defined as eGFR above the cut off value of the 5th quintile of the whole group. Results: In the GHF group eGFR(ml/min/year) decreased significantly more than in others (−3.4 (IQ−5.8 to −1.76 vs. −1.5 (IQ−2.6 to −0.3); total decrease −17.7% vs. −9.8%; per year −2.8% vs. −1.5%; all p < 0.001). ACR was non-significantly higher in GHF group at enter and at the end of follow-up (5.73 (IQ3.35–8.6) vs. 4.5 (IQ3.31–7.25); p = 0.06, 5.93 (IQ4.26–8.64) vs. 5.7 (IQ4.08–9.82; NS, respectively). In the GHF group, at the end of follow-up ACR did not increase significantly. At enter and at the end of follow-up BP was significantly lower in GHF group (p < 0.001). At the end of study we failed to observe difference in increase of BP and new-onset HT between GHF and others. Conclusions: In our group of healthy subjects GHF was associated only with more rapid decrease of GFR. No impact of GHF on ACR increase and development of new-onset HT in healthy subjects was observed. GHF has less prominent effect on HT and kidney function in apparently healthy subjects than in those with HT and metabolic disorder.

[PP.30.14] SALT CONSUMPTION IN CROATIAN CONTINENTAL RURAL POPULATION: ENAH STUDY

Objective: Results from our previous survey confirmed that salt consumption (24 h mapping) in Croatia is above 11 g/day. Salt intake was higher in rural than in urban area. Croatian national campaign started in 2008 and our aim was to analyze trends in salt consumption in rural area in the past period. Design and method: Out of 3056 subjects enrolled in ENAH study, 2259 (868m, 1391w) were eligible for further analysis. All inhabitants older than 18 years of age from this rural area were invited to participate and were examined on a door-to-door basis. Pregnant women, patients with terminal illness who were bed-ridden, patients with severe disability or those who have had at least one limb amputated or immobilized and mentally ill or suffering from dementia were considered ineligible. Participation rate was >70%. Salt intake (g/day) was estimated from the first morning spot urine using Intersalt equation. Blood pressure (BP) was measured using Omron 6 device following the ESH guidelines. Villagers were examined in 2008, 2010 and 2015 and trends in salt intake and association with BP were analyzed. There were no differences in age and gender between survey years. Results: In 2008, 2010, 2015 salt intake in the whole group was 10.5(8.7–12.2); 10.2(8.4–12.1); 10.9 (9.5–12.2), respectively; in men 10.4(8.8–12.2); 10.1(8.5–12.1);10.9 (9.3–12.3), respectively; in women 10.6 (8.6–12.3); 10.4(8.4–12.1); 10.9 (9.6–12.1), respectively. We failed to observe trend in decreasing salt intake, without gender difference. Significant correlation between salt intake and systolic and diastolic BP was found in the whole group (r = 0.32; r = 0.18, respectively, both p < 0.001), in men(r = 0.29; r = 0.134, respectively, both p = 0.01) and in women (r = 0.35; r = 0.21, respectively, both p < 0.001). Conclusions: We are fully aware of many drawbacks related to the spot urine sampling. However, using the same method and the same equation in the same population we believe that we can consider our results reliable to estimate the trend of salt consumption in rural area. Significant correlation with BP was observed which confirms prior results. Despite of the Croatian National Program launched 10 years ago, salt consumption in rural area is very high and remains unchanged and further efforts in this field are needed.

[OP.7A.05] TRENDS IN PREVALENCE, TREATMENT AND CONTROL OF HYPERTENSION IN CROATIAN CONTINENTAL RURAL POPULATION - ENAH STUDY

Objective: Overall prevalence of hypertension (HT) in Croatia is high and control of HT is poor. In this study our aim was to analyze trends in prevalence, treatment and control of HT in the same rural population during the 10 years long survey. Design and method: Out of 3056 subjects enrolled in ENAH study, 2361 were eligible for further analysis. All inhabitants older than 18 years of age from this rural area were invited to participate and were examined on a door-to-door basis. Pregnant women, patients with terminal illness who were bed-ridden, patients with severe disability or those who have had at least one limb amputated or immobilized and mentally ill or suffering from dementia were considered ineligible. Participation rate was >70%. Blood pressure (BP) and heart rate (HR) were measured using Omron 6 device following the ESH guidelines. HT was defined as a BP > = 140/90 mmHg, and/or current use of antihypertensive drugs. Treatment of HT was defined as usage of antihypertensive medication at the time of the interview. Control of treated HT was defined as BP < 140/90 mmHg. Villagers were examined in 2005, 2008, 2010 and 2015, and trends of prevalence, treatment and control were analysed. There were no differences in age and gender among various years groups. Results: Prevalence of HT decreased from 2005 to 2010 but still remains very high (64.1% vs. 55.2%; p = 0.04). Prevalence of treated HT significantly increased from 2005 to 2015 (26.8% vs. 68.5%; p = 0.001). Prevalence of controlled HT gradually increased and in 2005, 2008, 2010 and 2015 was 11.%, 14.5%, 15.1% and 17.3%, respectively; p = 0.09). Significant decrease in average systolic BP was observed (p for trend <0.001 for systolic BP). Conclusions: Prevalence of HT in Croatian rural area remains very high. Nowadays, much more HT were treated and there is trend to better control. However, results are still unacceptable. High salt consumption, obesity, poor socioeconomic status and low educational level are the most import causes of such thrashing result.

[OP.5C.04] HEART RATE IS ASSOCIATED WITH GLOMERULAR HYPERFILTRATION IN APPARENTLY HEALTHY SUBJECTS.

Objective: Glomerular hyperfiltration (GHF) was associated with progression of kidney disease and hypertension (HT). It was reported that high metabolic risk is related to increase of GHF. Our aim was to analyze in apparently healthy subjects which factor(s) influence (s) GHF and determine(s) clinical course in long-term prospective study. Design and method: Out of 954 subjects enrolled in ENAH follow-up study, 371 (137 m, 234w; mean age = 46years) were eligible for further analysis:100 with optimal, 72 with normal BP, 70 with PHT (high normal BP), and 129 with newly diagnosed untreated HT. Follow-up period was 77 ± 12 months. Exclusion criteria were treatment with antihypertensive drugs, diabetes, pregnancy, eGFR < 60 ml/min, CV or cerebrovascular incident, chronic terminal diseases, dementia, immobility and missing data. BP and heart rate were measured using Omron 6 device following the ESH guidelines. Uric acid, glucose, lipids, serum creatinine, hsCRP, leptin and adiponectin were determined; HOMA index was used to calculate insulin resistance and MDRD formula to estimate GFR. Albumin to creatinine ratio (ACR) was determined from the first morning spot urine. GHF was defined as eGFR above the cut off value of the 5th quintile of the whole group. Results: Subjects with GHF were younger (38.1 vs. 48 13), had smaller waist circumfernce (87 ± 17 vs. 92 ± 16), lower BP (121/76 vs. 131/81), total cholesterol (5.3 ± 1.1 vs. 5.8 ± 1.1) LDL-cholesterol (3.1 ± 0.9 vs. 3.5 ± 1.0) and leptin (C 5,1 (IQ2.8–10.7) vs. 10.4 (5.4–16.6) compared to others; all p < 0.05. Neither metabolic factors nor BP values were assosiated with GHF. However, GHF was positively associated with HR in a way that every 1 beat/min increases odds for hyperfiltration for 7% (1.07 [1.02, 1.13]) at baseline for 6% at the end of follow up (1.06 [1.01, 1.10]). Conclusions: Contrary to some reports from literature, our group of apparently healthy subjects with GHF did not have increased metabolic risk. Interestingly, according to our results heart rate is positively associated with GFH indicating that increased sympathetic activity might have important role.

[PP.03.05] SERUM URIC ACID IS NOT ASSOCIATED WITH ALBUMINURIA IN PREHYPERTENSION AND NEWLY DIAGNOSED HYPERTENSION

Objective: Elevated serum uric acid(SUA) even asymptomatic was found to be associated with blood pressure(BP), hypertension(HT), cardiovascular and chronic kidney disease. It was reported that xantin oxidase inhibitors(XOi) could in animals reverse glomerular hypertension and hypertrophy caused with hyperuricemia and in hyperuremic humans decrease microalbuminuria(MA). However, the question still remain whether elevated SUA is cause. marker, or just epiphenomen of renal impairment. Our aim was to analyze association of SUA with MA in prehypertensives(PHT) and newly diagnosed, untreated hypertensives(HT). Design and method: Out of 954 subjects enrolled in ENAH follow-up study, 371 (137 m, 234 w) were eligible for further analysis 100 with optimal, 72 with normal BP, 70 with PHT (high normal BP), and 129 with newly diagnosed HT. Exclusion criteria were treatment with antihypertensive drugs and XOi, diabetes, pregnancy, eGFR<60 ml/min, CV or cerebrovascular incident, chronic terminal diseases, dementia, immobility and missing data. BP was measured using Omron 6 device following the ESH guidelines. Fasting blood was analysed for SUA, glucose, lipids, serum creatinine, hsCRP. HOMA index was used to calculate insulin resistance and MDRD formula to estimate GFR. Albumin to creatinine ratio (ACR) was determined from the first morning spot urine. Results: In the whole group there is trend of lower ACR regarding SUA (1st vs. 2nd vs. 3rd tercile 5.78 vs. 5.11 vs. 4.65; p = 0.002). 78.3% subjects in the highest tertile of SUA were in the lowest tertile of ACR. Correlation of SUA and ACR was significantly negative (r = −0.21; p < 0.01), but after adjustment for age, gender, waist circumference, systolic BP, FBG, alpha1/CR significance was lost (beta = −0.09; p = 0.89). In the subgroup of PHT and HT SUA was also negatively correlated (r = −0.14; p = 0.02) but again the association was not significant after adjustment (beta = −0.10; p = 0.28). Trend of ACR across of SUA tertiles was the same as in the whole group (p = 0.02). Conclusions: In PHT and newly diagnosed, untreated HT, SUA is not associated with MA. Even more, our observation on negative association of SUA with MA might rise a provocative question whether in early phase of cardiorenal continuum elevated SUA, having antioxidative properties, might be even protective.

[OP.5B.09] ARISTOLOCHIC ACID NEPHROPATHY. A CASE OF SLOWER VASCULAR AGING?

Objective: Early vascular aging (EVA) is a feature of chronic kidney disease(CKD) and pulse wave velocity(PWV) is independent predictor of premature cardiovascular(CV) mortality. High blood pressure(BP) and vascular calcifications contribute mostly to EVA in this group. Endemic nephropathy(EN), an environmental form of aristolochic acid nephropathy, is a chronic tubulointerstitial salt wasting nephropathy characterized with later onset and milder forms of hypertension (HT), and in line with this we hypothesized that arterial stiffness progresses slowlier in EN pts resulting in lower CV mortality. Design and method: A total of 186 hemodialysed(HD) patients (90m, 96w; 67.35+13.07years) were enrolled. At the end of follow up, after 25 months, 97 pts were alive (52EN and 45non-EN). All patients were dialysed by the international guidelines. Brachial BP was measured with Omron M6 device and PWV was determined by Arteriograph before mid-week dialysis. Results: There were no differences in gender, smoking status, type of vascular access, phosphate binder doses, vitamin D and dialysis modalities between two groups. At baseline and at the start of HD EN pts were significantly older (72. ± 37.1 vs 62.8 ± 15.1; p < 0.001), had shorter duration of HT prior commencement of HD than non-EN pts (36 vs. 84 months; p < 0.001). There were no differences in BP, but EN pts were treated with less antihypertensive drugs (p < 0.01). EN pts had lower values of P and CaxP (all p < 0.001) and significantly lower PWV values at baseline and at the end of follow-up period (9.2 ± 1.6 vs. 10.5 ± 1.9; 9.3 ± 1.3 vs. 10.5 ± 1.9, respectively; both p < 0.001). In multivariate analyses EN was independent predictor of high PWV. During the study period EN patients died significantly less frequently from CV events (12%vs.32%; p = 0.001), and had longer mean survival time (22.3 vs.18.2 months, p < 0.001). CV mortality was significantly lower in EN group (15.0% vs. 37.8%, HR0.32 [0.18,0.59], log-rank p = 0.0004), which remained significant after adjustment for other risk factors (aHR0.17 [0.06,0.49]). Baseline PWV > 10m/s was associated with higher risk for CV mortality(aHR1.88[1.42,2.49]). Conclusions: Despite being older EN patients had lower PWV values. In EN, later onset of HT during predialytic clinical course, milder form of HT and better control of phosphate during HD therapy slowdown vascular aging and thus CKD progression, and importantly resulting in lower CV mortality and longer survival time. Opposite to EVA in other CKD, EN might be the case of slower vascular aging.

PS 14-88 BLOOD PRESSURE PREDICTS NEW-ONSET CHRONIC KIDNEY DISEASE INDEPENDENTLY OF METABOLIC SYNDROME – LONGITUDINAL DATA FROM THE CROATIAN RURAL STUDY (ENAH)

Objective: Chronic kidney disease (CKD) and metabolic syndrome (MetSy) are important predictors of mortality. Our objective was to assess the predictors of new onset CKD in rural population with and without MetSy. Design and Method: Out of 954 subjects enrolled in ENAH follow-up study, 521 (147 m, 374 w) were eligible for further analysis and followed up for total of 3333 person-years (median 7 (5–7) years). Exclusion criteria were pregnancy, CV or cerebrovascular incident and chronic terminal diseases. Blood pressure (BP) was measured using Omron M6. Fasting blood was analysed for glucose, lipids, serum creatinine and other parameters. MetSy was diagnosed according to NCEP-ATP III criteria. Results: Prevalence of MetSy at baseline was 24.0% being similar in men and women (24.6% vs. 22.4%, p = 0.35). The prevalence of individual MetSy components in subjects with MetSy were: high BP (88.9%), pathological WC (81.6%), high FBG (60.0%), high TG (48.8%) and low HDL-C (30.4%); women having pathological WC more frequently (98.9% vs. 87.9%, p = 0.017). The incidence rate of new onset MetSy was 3.7% per year. Prevalence of CKD at baseline in our group was 5.6%, being similar in subjects with MetSy and controls (8.1% vs 5.1%, p = 0.13). Contrary to this, 31 subjects developed new onset CKD for an incidence rate of 1.0% per year and an incidence almost 2.5-fold higher in subjects with MetSy (11.5% vs. 4.8%, p = 0.02). There was no difference in number of MetSy components or their individual prevalence between CKD and non-CKD subjects (p > 0.05). In whole group, BP (OR 3.0,95% CI 0.9,10.0) and older age (OR 1.2,95% CI 1.1,1.3) were predictors of new onset CKD. Conclusions: MetSy is highly prevalent in Croatian rural population and frequently associated with CKD. Beside age, BP is predictor of new-onset CKD. Dietary and BP lowering population-level strategies might show efficient in preventing not just MetSy, but to a certain extent CKD.