Z. Dika

[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.

4D.11: ARTERIAL STIFFNESS IN PATIENTS WITH ENDEMIC NEPHROPATHY UNDERGOING HEMODIALYSIS.

Objective: Arterial stiffness (AS) is an independent risk factor of cardiovascular mortality in general and haemodialysis (HD) population. Endemic (Balkan) nephropathy (EN) is a chronic tubulointerstitial salt wasting nephropathy characterized with later onset of arterial hypertension (AH) which could also affect AS. Thus our aim was to analyse AS in EN patients compared with other end-stage renal disease patients undergoing HD. Design and method: A total of 186 HD patients (90 m, 96 w; 67.35 + 13.07 years) from 3 dialytic units and 2 endemic areas were enrolled. The exclusion criteria were: duration of dialysis < 3 months, atrium fibrillation, myocardial infarction or stroke in last 3 months, heart failure, arteriovenous anastomosis besides functional arteriovenous fistula. EN was diagnosed by modified WHO criteria. All patients were dialysed by European and KDIGO guidelines. Brachial blood pressure (BP) was measured with Omron M6 device and AS markers; pulse wave velocity (PWV) and aortic augmentation index (AIx) were measured by Arteriograph before mid-week dialysis. Results: There were no differences in sex, smoking status, type of vascular access, phosphate binder doses, vitamin D, hypertension and brachial BP between two groups. Non-EN patients had more antihypertensives drugs (p < 0.001), higher body mass index, waist circumference and diabetes. There were no differences in dialysis modalities except lower ultrafiltration in EN patients (p < 0.001). EN were significantly older (p < 0.001) with later start of dialysis. EN had lower values of phosphates (p < 0.001), CaxP (p < 0.001) and iPTH (p < 0.001), and significantly lower PWV (9.2 ± 1.6 vs.10.5 ± 1.9; p < 0.001). Using multiple linear regression models EN was the most significant independent negative predictor for PWV (p < 0.001) and AIx (p = 0.002). Using logistic regression non-EN patients had odds ratio for increased AS (PWV > 10 m/s OR 3.12; 1.72–5.82; p < 0.00001). Conclusions: EN patients despite being older had lower PWV and AIx values. Even more, EN is an independent predictor of lower arterial stiffness. This could be explained with later onset of AH in pre-dialytic clinical course and probably with lower phosphate values due to tubulopathy. Better control of Ca and P during dialysis also contributes to observed lower AS in EN patients undergoing HD.

Arterial stiffness in atherosclerotic renovascular hypertension.

Objective: Arterial stiffness is an independent cardiovascular risk factor. Aging, high blood pressure and increased renin-angiotensin system activity contribute to increased arterial stiffness in patients with atherosclerotic renovascular hypertension (aRVH). A literature search failed to identify any study related to this topic. Therefore, our aim was to determine the arterial stiffness in patients with aRVH and analyze whether stenting in addition to multifactorial drug therapy has beneficial effects on markers of stiffness and the clinical course. Methods: In this 6-month longitudinal study, 37 patients with refractory hypertension and unilateral aRVH were enrolled. After stenting, all patients received multifactorial dug therapy including 80 mg of telmisartan. Arterial stiffness indices were determined using Arteriograph. The control group consisted of 44 patients with essential hypertension. Results: There were no differences in brachial blood pressure values between the two groups (P > 0.05). At baseline, adjusted pulse wave velocity (PWV) was higher in aRVH patients than that of essential hypertensive patients (12.8 ± 0.4 vs. 11.6 ± 0.3 m/s; P = 0.029). In the aRVH group, at the end of the follow-up, a significant decrease in the aortic augmentation index (37.7 ± 9.9 vs. 33.7 ± 11.4; P = 0.02) without changes in PWV was observed (P > 0.05). Conclusion: This study is the first to show that arterial stiffness is higher in patients with refractory aRVH than in those with essential hypertension. Multifactorial therapy based on stenting and intensive medical treatment reduced central blood pressure and augmentation index. Failure to obtain PWV reduction is likely a consequence of the present irreversible structural vessel changes. Longer follow-up might enable us to resolve whether arterial stiffness indices have better predictive ability in patients with aRVH than brachial blood pressure.

NEGATIVE TREND IN ASSOCIATION OF UROMODULIN WITH BLOOD PRESSURE IN PREHYPERTENSIVES AND UNTREATED HYPERTENSIVES WITH NORMAL KIDNEY FUNCTION

Objective: Uromodulin and minor G allele UMOD gene rs13333226 have been associated with blood pressure (BP), hypertension (HT) and better renal function. Our aim was to analyze the association of uromodulin and the frequency of G allele with BP and kidney function in untreated subjects with a normal glomerular filtration rate (GFR). Design and method: From 894 participants of the ENAH follow up, a cohort group of 559 untreated subjects (men 55.8 %, cohort group mean age 38.6) with an eGFR > 60 ml/min/1.73m2 (CKD Epi equation) were enrolled into the study. Subjects were divided in three subgroups: optimal BP (OBP; N = 107), prehypertension (PHT; N = 145) and HT (N = 307). UMOD genotyping rs12917707polymorphism was performed by RT-PCR with the fluorescence-based TaqMan system, while urinary uromodulin levels were measured by Enzyme Linked Immunosorbent Assay (ELISA). Results: We failed to find difference in uromodulin levels among BP categories. However, a negative association of uromodulin with systolic BP (NS) and diastolic BP (r = 0.20; p = 0,069) was observed in the entire group. No association between uromodulin and eGFR was noted. Uromodulin was found to be lower in women than men. The frequency of A and G alleles was 83.2% and 16.8%, respectively. No difference in the frequency of G allele was found among the BP categories. A trend of higher uromodulin was observed in homozygous for the G allele. No significant trend was observed between uromodulin and eGFR in the entire group. Conclusions: There is trend of negative association of uromodulin with BP in middle-aged untreated subjects with normal kidney function. We did not find an association of uromodulin with eGFR. A trend of a higher uromodulin urine concentration was observed in subjects with the G allele of UMOD rs13333226.

FIXED DOSE COMBINATION THERAPY IS ASSOCIATED WITH BETTER BLOOD PRESSURE CONTROL AND LOWER ALBUMINURIA IN REAL-LIFE COHORT DURING 7 YEARS OF FOLLOW UP. ENAH – CROATIAN RURAL STUDY

Objective: The aim of this study was to analyze differences in blood pressure (BP) control and albuminuria between subjects treated with fixed dose combination (FCD) and those treated with free components in real-life during the 7 years follow up period. Design and method: Out of 1134 subjects (door-to-door enrollment, participation rate 80%) data on 236 (54 men; 182 women; mena age 63.2 years) treated hypertensives (HT) were analyzed at the end of 7 years of follow-up. At enter 136 of them were already treated HT (group A) and 100 were new-diagnosed HT (group B) who had started with antihypertensive therapy from that moment. Local GP were allowed to tailor antihypertensive therapy during the follow up period. At basal and at the end of follow up BP was measured by physicians who were project collaborators (ESH/ESC guidelines; OmronM6); salt intake (spot urine - Kawasaki equation), eGFR (CKD-Epi) and albumin-to-creatinin ration (ACR mg/g;first morning urine sample) were analyzed in central lab. Pregnant women, terminal ill, bed-ridden patients, those with severe disability, mentally ill or suffering from dementia or at least one limb amputated/immobilized were exclided. Results: At the end of follow up BP controll was achieved in 31.6% and 38% of HT (group A and B, respectively). In both groups, there there were no significnat differences in salt intake, BMI, smoking and the number of used drugs between controlled and uncontrolled subjects (p < 0.05). However, in group A significant increase in FDC prescription was observed ih the controlled vs.uncontrolled subjects (22% vs. 5.5%). BP control was associated with lower ACR in group A (14.9 vs.76.3; p < 0.01) and group B (9.1 vs.24.9; p < 0.05). Conclusions: In this real-life cohort after 7 years of follow-up BP controll was ahived with more drugs but only if used as FDC what was associated with better organoprotection i.e.lower ACR. Overall poor BP control and organoprotection could be improved using more FDC.

[PP.30.29] PREHYPERTENSION AND SINGLE NUCLEOTIDE POLYMORPHISM RS13333226 OF THE UROMODULIN (UMOD) GENE

Objective: Single nucleotide polymorphism of UMOD gene rs13333226 and its G minor allele were found to be associated with lower blood pressure (BP) values. The aim in this study was to analyze the relationship of this polymorphism with prehypertension (PHT) in general population and here we are reporting preliminary cross-sectional results. Design and method: Out of 3056 subjects enrolled in ENAH study, 496 were eligible for further analysis. Exclusion criteria were treatment with antihypertensive drugs, diabetes, pregnancy, eGFR<60 ml/min, cardiovascular 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. PHT was defined following the JNC 7 guidelines as a BP >=120/80 and <140/90 mmHg, and normotension (NT) as a BP <120/80 mmHg. Clinical and laboratory data were obtained by routine methods and polymorphism was obtained with TaqMan® real time PCR method. Results: Prevalence of genotypes and G minor allele in overall population were A/A 68.5% (N = 340), A/G 29.6% (N = 147), G/G 1,8% (N = 9) and G minor allele 16% (N = 165). Distribution of all genotypes and G minor allele did not differ significantly between groups of participants with PHT and NT. Logistic regression showed that none of the observed genotypes were predictors for PHT. Common risk factors such as gender, age and body mass index affect systolic BP and the estimated glomerular filtration in all genotypes equally. Conclusions: We failed to find neither an association of uromodulin gene (SNP rs13333226) with BP in normotensive subjects nor this SNP was predictor of prehypertension. In this ongoing study we will enlarge the sample what might enable us to detect small changes in BP phenotype, and in follow up period will analyze predictive value of this polymorphisms for development of sustained hypertension.

[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.