Gernot Pichler

Influence of obesity in central blood pressure.

Background: Obesity is an important risk factor for cardiovascular disease and has become a major concern in healthcare due to its high prevalence worldwide. The aim of the present study was to investigate the impact of BMI on central blood pressure (BP) and pulse wave velocity (PWV) in normotensive and hypertensive patients. Patients and methods: Normotensive and hypertensive adult patients who attended the outpatient clinic of cardiovascular risk were included. Peripheral BP was obtained in the brachial artery by using an oscillometric device (OMRON M-6). Central aortic BP waveform was reconstructed from the radial artery pressure waveforms (SphygmoCor, AtCor Medical, Sydney, Australia) and central BP was calculated. Carotid–femoral PWV was measured by an automatic device (Complior, Artech, France). Results: We examined a total of 351 patients [50.7% women; 77 patients normal-weight (BMI < 25 kg/m2)], 274 patients overweight or obese (BMI ≥25 kg/m2). Central SBP showed a positive association with male sex and mean BP, but a negative association with overweight/obesity. PWV was positively associated with age, male sex, central BP, peripheral BP and BP treatment, whereas BMI of at least 25 kg/m2 led to a decrease in PWV in patients with the same central SBP levels. Likewise, PWV was lower in the overweight/obese group compared to the normal-weight group at the same central SBP. Conclusion: Overweight and obesity tend to have lower central SBP as compared to lean patients, mainly in women. Further research is required to assess the interaction between body weight and vascular dynamics and their clinical implications.

Carotid-femoral pulse wave velocity assessment by two different methods: implications for risk assessment.

Introduction: Several devices are available for carotid–femoral pulse wave velocity (cfPWV) measurement, and a cut-off value for reference cfPWV has been established. However, discrepancies between devices have been reported. Objectives: The aim of the study was to establish the concordance of two common techniques (Complior and SphygmoCor), taking into account the anatomical distance between the measurement sites, and to investigate the impact on cardiovascular risk stratification. Methods: cfPWV, central and peripheral blood pressure were assessed in patients attending the hypertension outpatient clinic. The subtracted carotid–femoral distance was estimated both according to the manufacturers recommendations and correcting the obtained values by 10.3%. Bland–Altman plots, Pearsons correlation coefficient, Lins concordance correlation coefficient and multivariate models were used to investigate the difference in cfPWV. Results: cfPWV assessed in 118 patients (age 55 ± 12 years, 61% hypertensive patients, BMI 28.9 ± 4.4 kg/m2) with the Complior device was lower than that assessed with the SphygmoCor device, regardless of correcting the subtracted carotid–femoral distance (8.7 vs. 10.3 m/s and 9.3 m/s, respectively; P value < 0.001). The average difference was −1.59 ± 1.5 and −0.617 ± 1.39 m/s for corrected and uncorrected SphygmoCor values, respectively, SBP, BMI and female being the main determinants of the difference. Cardiovascular risk stratification changed in up to 40% of the study population, depending on the device and the arterial distance estimation. Conclusion: The concordance between the Complior and the SphygmoCor device is poor when the anatomical artery length is controlled for and in the presence of cardiovascular risk factors, resulting in a difference in classification of cardiovascular risk.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

Background. Patients undergoing hemodialysis and kidney graft recipients are high‐risk populations for cardiovascular and all‐cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein‐7 (BMP‐7) are bone‐ and vascular‐derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta‐analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. Methods. Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time‐to‐event data [hazard Ratio (HR)] or as effect size with a fixed time of follow‐up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. Results. From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all‐cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all‐cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP‐7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. Conclusions. In hemodialysis patients, FGF23 is a predictor of all‐cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.

Comparative study of the efficacy of olmesartan/amlodipine vs. perindopril/amlodipine in peripheral blood pressure after missed dose in type 2 diabetes

Introduction: Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped. Objectives: The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed. Methods: In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20–40 mg/amlodipine 5–10 mg or perindopril 4–8 mg/amlodipine 5–10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration. Results: The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination (−11.7 and −10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group. Conclusions: The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine.

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study

BACKGROUND We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. METHODS We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. RESULTS After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04-1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15-1.55) for IRAE; HR 1.38 (1.06-1.79) for IURAE; HR 1.62 (1.22-2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. CONCLUSIONS IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment.

POPULATION ATTRIBUTABLE RISK FOR CARDIOVASCULAR DISEASE ASSOCIATED WITH HYPERTENSION. RESULTS FROM THE HORTEGA FOLLOW-UP STUDY

Objective: Hypertension (HTN) is the worldwide leading risk factor for cardiovascular morbidity and mortality. As a modifiable risk factor, epidemiological measures derived from cohort studies are important to influence policymakers. OBJECTIVE: To determine the population attributable risk (PAR) for cardiovascular disease associated with hypertension. Design and method: We included 1244 subjects (mean age 52.3 y, 51% females), who participated in Hortega 13 years Follow-Up Study. HTN was defined as a blood pressure greater than or equal to 140/90 mmHg for systolic and diastolic blood pressure or the use of antihypertensive medication. We used Cox proportional hazard analysis adjusted for traditional CVD risk factors to determine the association of HTN with incident CVD cases. The primary endpoint was incidence of fatal and non-fatal CV events. Due to the presence of confounding factors, the PAR was calculated as pd*(HR-1)/HR and 95% confidence interval was calculated using Bonferroni inequality method. Hazard Ratio (HR) estimates and HTN prevalence among cases (pd) were used to calculate sex-specific PARs for heart failure (HF), coronary heart disease (CHD) and stroke. Results: In our population, overall prevalence of hypertension was 34.7% (n = 211) and 34.1% (n = 217) for men and women, respectively. The HR for all CVD and the PAR associated with HTN was 1.89 (95% CI 1.63, 2.18) and 33.1 (95% CI 22.1, 43.8) respectively in men and 1.71 (95% CI 1.4, 2.09) and 33.8 (95% CI 19.4, 47) in women. The HR for CHD plus stroke and PAR associated with HTN was 1.7 (95% CI 1.42, 2.02) and 27.3 (95% CI 14.7, 40.6) in men and 1.91 (95% CI 1.48, 2.46) and 38.3 (95% CI 19.4, 54.6) in women. The HR for HF and PAR associated with HTN was 3.2 (95% CI 2.11, 4.83) and 57.4 (95% CI 31.3, 75) in men and 3.97 (95% CI 2.4, 6.56) and 69.4 (95% CI 41.6, 83.5) in women. Conclusions: In our population, approximately 33% of incident CVD is attributable to hypertension. This study emphasizes the role of hypertension as agent in different cardiovascular diseases, with a burden of up to 70% in women with heart failure.

[OP.3C.05] LDL-PARTICLES COMPOSITION AND INCIDENT CARDIOVASCULAR DISEASE IN A SOUTH-EUROPEAN POPULATION: THE HORTEGA-LIPOSCALE STUDY

Objective: The use of LDL-cholesterin particles (LDL-p) for cardiovascular risk prediction has been tested in high risk populations. The objective of this study was to evaluate the association of LDL-p and LDL-p composition with incident cardiovascular disease in adults participating in the Hortega Follow-up Study, a cohort study representative of a general population from Spain. Figure. No caption available. Design and method: “Standard” lipid levels (plasma total cholesterol, HDL-cholesterol, and triglyceride concentrations) were determined using a Hitachi 917 analyzer. The number and size of lipid particles were measured by nuclear magnetic resonance using LIPOSCALE algorithm (Biosfer Teslab, Reus, Spain). The association of lipid levels and LDL-particles composition with incident cardiovascular disease was assessed. Results: A total of 1162 subjects (49% male, mean age 49.7 years) was included into the study. LDL-p distribution was as followed: Small LDL-p was predominant (40–70%), followed by Medium LDL-p (20–40%) and Large LDL-p (10–20%). During a mean-follow up of 12.4 ± 3.3 years, a total of 159 CV events occurred. LDL particle size was related to all events when traditional cardiovascular risk factors were controlled for. Medium LDL-p, but not Small LDL-p, increased the risk of CHD and stroke in all statistical models. The relevance of Medium LDL-p was further evaluated in a compositional analysis using a leave-one-out approach. The highest risks were observed for LDL-p and CHD when the proportions of Medium and Small LDL-p were entered simultaneously into the model, which reflects an increase in the proportion of Medium LDL-p and Small LDL-p by a corresponding decrease in the proportion of Large LDL-p, respectively. That shift from Large to Medium and Small LDL-p proportions was associated with an increase in risk for CHD of 70% and 46%, respectively (figure 1). Conclusions: In a representative sample of the general population from Spain, NMR-measured LDL-particle size and composition were associated with cardiovascular outcomes. An increase in the proportion of Medium LDL-particles and Small LDL-particles by a corresponding decrease in the proportion of Large LDL-p was strongly associated with CHD. Further research is needed to elucidate the causal pathways underlying these associations.

[OP.2A.01] URINE CADMIUM LEVELS AND ALBUMINURIA IN A GENERAL POPULATION FROM SPAIN: A GENE-ENVIRONMENT INTERACTION POPULATION-BASED STUDY.

Objective: Chronic exposure to low levels of cadmium is an increasingly recognized concern, as cadmium biomarkers at relatively low concentrations have been associated with a number of health conditions including cancer and bone, kidney and cardiovascular disease. The aim of the present study was to evaluate the cross-sectional association between urine cadmium and albuminuria in a representative sample of the general population from Valladolid (Spain), and to test the hypothesis that specific genotypes in candidate genes related to oxidative stress may confer increased susceptibility to cadmium. Figure. No caption available. Design and method: Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS). Urine albumin was measured by automated nephelometric immunochemistry. 396 single nucleotide polymorphisms (SNPs) from 92 oxidative stress and albuminuria-related candidate genes were genotyped by SNPlex. Results: 1397 participants (mean age 49.7 ± 0.2, 49% males, 35.9% hypertensives, 5.6% diabetics, 44.6% never smokers) were included. The prevalence of albuminuria (albumin-creatinine ratio greater than or equal to 30 mg/g in women and greater than or equal to 20 mg/g in men) was 30%. The median levels of urine cadmium was 0.39 (IQR, 0.23–0.65) microgram per gram of creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to lowest tertiles of urine cadmium were 1.63 (95% CI, 1.43–1.85) and 2.92 (95% CI, 2.56–3.33), respectively (P for trend <0.001). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria (figure 1). At the Bonferroni-corrected level, significant differential associations of urine cadmium levels and albuminuria by genotipes of rs4720672 polymorphism in RAC1 gene were observed. Conclusions: Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Certain genotypes may confer differential susceptibility to potential cadmium effects.

Unusual Case of Severe Hypertension in a 20-Year-Old Woman

### G. Pichler A 20-year-old woman was seen in the emergency department because of abdominal pain and hypertension. The patient had no notable medical history, and there were no inherited disorders in her family. She had been well until 1 month before admission, when a sharp, constant, and diffuse abdominal pain developed. The pain was not modified by food intake, defecation or positional changes. The patient did not report anorexia, nausea, retching, or changes in her bowel habits. She had not experienced menstrual disorders or irritative urinary symptoms. Two days before admission a mild generalized headache developed. The patient had been seen in the emergency department 9× since the onset of symptoms, being discharged with different diagnosis including cystitis and nephritic colic among others. Abdominal ultrasonography was normal, and the gynecological evaluation did not show abnormalities. Over the past month, she had been prescribed analgesics and nonsteroidal anti-inflammatory drugs, prokinetics, spasmolytics, and antibiotics, without clinical improvement. At admission, on physical examination, the patient was alert, uncomfortable but cooperative. Temperature was 36.3°C, blood pressure (BP) was 166/111 mm Hg, pulse was 120 bpm, respiratory rate was 18 breaths/min, and oxygen saturation was 98%. The abdomen was soft and nondistended, with soft bowel sounds and absence of bruits, without hepatomegaly or splenomegaly, or signs of peritoneal inflammation. Peripheral pulses were regular and symmetrical without carotid-femoral delay. The neurological examination did not reveal any abnormality. The laboratory test showed mild hyponatremia (serum sodium, 126 mmol/L) with normal potassium levels (3.8 mmol/L), mild elevation of transaminases and mild leukocytosis (white-cell count, 15 100/mm3 with 80.1% segmented neutrophils), the rest of the analytic profile was normal (Table S1 in the online-only Data Supplement). Electrocardiography tracing on sinus rhythm was without signs of left ventricular hypertrophy or myocardial ischemia. Cerebral computed tomographic scan revealed bilateral hypodense lesions in …