Cardiovascular Organ Damage Research Articles

Target-organ damage and incident hypertension: the Korean genome and epidemiology study.

Hypertension is associated with cardiovascular organ damage. However, data are scanty on whether individual forms or combinations of subclinical target organ damage (TOD) increase the risk of incident hypertension in nonhypertensive study participants. A total of 1785 nonhypertensive participants from the fourth biennial examination (2007-2008) of the Korean Genome and Epidemiology Study were followed-up for four years. Echocardiographic left ventricular (LV) hypertrophy, LV diastolic dysfunction, increased carotid intima-media thickness (cIMT), and brachial-ankle pulse wave velocity (baPWV) were defined according to the current guidelines. During 4-year follow-up, 19.9% of participants developed hypertension. In multivariate Cox proportional hazards models, the adjusted hazard ratios for developing hypertension were 1.39, 1.66, 1.48, and 0.78 for higher values of the LV mass index, cIMT, baPWV, and tissue Doppler e' velocity, respectively (all P < 0.01). The hazard ratios for LV hypertrophy, LV diastolic dysfunction, cIMT >75th percentile, and baPWV ≥ 1400 cm/s were 1.61, 1.30, 1.86, and 2.07, respectively (all P < 0.05). Compared with participants without any TOD, those with combinations of TOD types had significantly greater risk for developing hypertension (hazard ratio = 2.12 and 3.98 for 1-2 and 3-4 TOD sites, respectively, all P < 0.001). In the nonhypertensive population, each subclinical form of TOD independently predicts incident hypertension. In addition, the combinations of various forms of TOD are associated with stepwise increases in the risk for developing hypertension. The results suggest that asymptomatic TOD does not always exist in an intermediate stage in the cardiovascular continuum.

0145: Evaluation of the relationship between renal resistive index and cardiovascular organ demage in hypertensive patients

Detection of target damage plays a key role in the evalation of overall risk, and therefore in the management of patient with primary hypertension.Evaluation of vascular at different sites of the renal parenchyma may suggest funtionnal or structural changes within the kidneys and could provide useful diagnostic and pronostic information. We evaluated the relatonship betwwen the renal resistive index (RRI) of intrarenal vasculature and the cardiovascular organ damage such as left ventricular hypertrophy (LVH), the diastolic dysfunction, microalbunuria, carotid atherosclerosis and the hypertensive retinopathy in hypertensive patients. 300 hypertensive patients underwent echocardiography with conventional Doppler and Doppler tissue imaging (DTI), carotid and renal ultrasonograpy and a bottom of eye.In addition, lipids profile, creatinine in serum, and urinary albumin concentrations were determinate.The patients were divided according to their RRI values in two groups: <0.70 and ≥0.70. Subjects with high RRI were older, had higher systolic and pulse pressure and more years of hypertension, compared to those with low RRI (p<0.0001). Patients with the higher RRI showed and increased left ventricular mass index(LVMI)and carotid intima media thickness with a higher prevalence of LVH with a beginning of deterioration of diastolic function, carotid plaques and microalbuminuria (p<0.0001). Age, systolic and pulsated pressure, carotid repercussion, LVMI and microalbuminuria were independently relatedto RRI. RRI, especially the higher values, are positively correlated with target organ damage in hypertensive patients.The evlaution of RRI could predict the presence of early cardiovascular damage.The RRI would be a criter of substitution for the estimate of the total cardiovascular risk.

A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy.

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%–12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.

Percentiles for central blood pressure and pulse wave velocity in children and adolescents recorded with an oscillometric device

Objective: In adults with arterial hypertension, measuring arterial stiffness by pulse wave velocity (PWV) can determine the extent of cardiovascular subclinical organ damage. PWV has independent predictive value for cardiovascular events, but there are currently no recommendations for measuring PWV in children. In addition, central systolic blood pressure (cSBP) strongly reflects vascular changes. The aim of this study was to establish percentiles for cSBP and PWV in children and adolescents to evaluate and classify altered vascular function in youths. Methods and results: We measured PWV and cSBP with an oscillometric device with inbuilt ARCSolver-algorithm (estimated by using the brachial waveform) and calculated smoothed reference percentiles for 1445 children and young adults (49.5% female; 13.41 ± 2.80 years, range 8–22 years; PWV 4.67 ± 0.34 m/s; cSBP 100.7 ± 8.9 mmHg) using the LMS-method based on age and height. PWV and cSBP increased with age and height, but slightly differently for girls and boys, possibly reflecting different growth patterns. Between 8 and 21 years, PWV increased from 4.29 ± 0.32 to 4.98 ± 0.33 m/s in girls and from 4.27 ± 0.18 to 5.22 ± 0.46 m/s in boys. While girls showed a minor increase in cSBP (91.2 ± 7.5 to 109.1 ± 8.6 mmHg), the cSBP in boys ranged from 90.0 ± 5.8 to 110.5 ± 9.6 mmHg with a more pronounced increase between 14 and 17 years. Conclusion: These percentiles for PWV and cSBP can help define arterial stiffness in youths and contribute to risk stratification for cardiovascular disease. For example, in children with prehypertension or isolated systolic hypertension, PWV and cSBP can provide additional information about the function of the vascular system, thereby strengthening intervention strategies.

Association between noninvasive fibrosis markers and cardio-vascular organ damage among adults with hepatic steatosis.

Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12–13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22–10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors.

Predicting cardiovascular mortality in chronic kidney disease (CKD) patients.

Cardiovascular mortality in chronic kidney disease (CKD) patients is a critical clinical challenge due to poor clinical outcome and increasing prevalence. Nephrologists and transplant specialists need suitable biomarkers to predict the occurrence of cardiovascular events and/or mortality in practice. At the technical level, development of a non-invasive repetitive sampling procedure is required to develop applicable biomarkers, offering a platform for clinicians to dynamically monitor the alteration of patient condition. Apart from specificity and sensitivity, the ideal biomarkers should be independent of various confounders such as sex, sex, age, kidney function, diabetes, and blood pressure. This article reviews recent studies on the identified potential biomarkers to analyze their predictive value and significance. The present study revealed that the identified potential biomarkers are involved in magnesium and phosphate metabolism, hormone dysregulation, pro-inflammatory process, and cardiovascular pathogenesis. Combined use of those biomarkers might allow early identification of subclinical cardiovascular system organ damage, effectively predict cardiovascular mortality, and significantly deepen our mechanistic understanding of the occurrence of cardiovascular events and mortality, which will help to develop preventive measures.

Abstract 19119: Augmentation Index is Associated With Renal Function in Black but Not in White Young Adults: The Bogalusa Heart Study

Background: Increased Augmentation Index (AI) has been associated with kidney damage in patients with hypertension and underlying cardio-metabolic diseases. However, information is scant on the association between AI and renal function/performance in non-institutionalized asymptomatic young adults. Hypothesis: Race-specific differences exist on the association between AI and renal function (as defined by estimated glomerular filtration rate (eGFR)), in asymptomatic young adults. Methods: As a part of the Bogalusa Heart Study, a long term community based study, 884 non-institutionalized participants with a mean age of 43.5 years (29.4-51.3), 68.3% whites and 41.9% male were considered. AI was estimated non-invasively by applanation tonometry of the radial artery. eGFR was calculated using the MDRD study equation. Race-specific independent association of AI with eGFR was tested through multivariable adjusted linear regression analyses. Results: Black participants had higher AI and eGFR levels compared to whites. Of note, black females had significantly higher levels of AI and eGFR compared to black males (p&lt;0.01). No significant sex differences were noted in white participants. In multivariable adjusted linear regression analyses, controlling for age, sex and traditional cardiovascular risk factors, AI was significantly and directly associated with eGFR in blacks (B=1.12, p&lt;0.001), but not in whites (B=0.039, p=0.34) Conclusion: The observed differences in the impact of AI on renal function help support the hypothesis that underlying mechanisms for cardiovascular disease related-end organ damage differ among race groups. Further, this may aid to enhance race-specific approaches on prevention and screening of cardiovascular disease and complications.

Microalbuminuria, but not reduced eGFR, is associated with cardiovascular subclinical organ damage in type 2 diabetes

AimThis study explored the association between reduced estimated glomerular filtration rate (eGFR) and microalbuminuria vs. subclinical organ damage in patients with type 2 diabetes. MethodsData from middle-aged patients with type 2 diabetes (n=706) treated in primary care were analyzed for microalbuminura, defined as a urinary albumin/creatinine ratio (uACR)≥3.0mmol/mol, and reduced eGFR, defined as<60mL/min/1.73m2, in relation to blood pressure, pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima–media thickness (IMT) and lumen diameter (LD). ResultsPatients with microalbuminuria had significantly higher 24-h ambulatory systolic blood pressure (ASBP) compared with subjects with uACR<3mg/mmol: 137 vs. 128mmHg (P<0.001). There were no differences in ASBP in patients with eGFR<60mL/min/1.73m2. However, patients with vs. without microalbuminuria had increased PWV (11.4 vs. 10.1m/s; P<0.001), LVMI (134.4 vs. 118.6g/m2; P<0.001), LD (7.01±0.93 vs. 6.46±0.74mm; P<0.001) and IMT (0.78 vs. 0.74mm; P=0.047), respectively. The associations between uACR vs. PWV and LVMI were more robust after adjusting for age, diabetes duration, ASBP, HbA1c, LDL-cholesterol, and antihypertensive and lipid-lowering therapy compared with uACR vs. IMT. There were no statistically significant differences in PWV, LVMI or IMT between patients with reduced (<60mL/min/1.73m2) vs. normal eGFR. ConclusionLevels of urinary albumin excretion, but not reduced eGFR, were associated with increased arterial stiffness, left ventricular mass and atherosclerosis in patients with type 2 diabetes.

Nocturnal Hypertension or Nondipping: Which Is Better Associated With the Cardiovascular Risk Profile?

Both increased night blood pressure (BP) and nondipping are associated with worse cardiovascular risk and prognosis. However, as they are often related features, their relative importance has been difficult to assess separately. In this study we address separate associations of nocturnal hypertension and nondipping with cardiovascular risk profile in treated and untreated hypertensive patients. A total of 37,096 untreated patients and 62,788 patients receiving antihypertensive treatment from the Spanish Ambulatory Blood Pressure Monitoring Registry were included. Each cohort was separated into 4 groups: group 1, night systolic blood pressure (SBP) <120 mm Hg and normal dipping (>10%); group 2, night SBP <120 mm Hg and nondipping (≤10%); group 3, nocturnal hypertension (SBP ≥120 mm Hg) and normal dipping; and group 4, nocturnal hypertension and nondipping. The smallest proportion of patients with additional cardiovascular risk factors, organ damage, and history of previous events was observed in the group with both normal night SBP and dipping, whereas those with both nocturnal hypertension and nondipping showed the largest proportion of cardiovascular risk factors and diseases. When groups showing only 1 abnormality were compared, nondipping was associated with female sex, reduced renal function, and previous cardiovascular events, whereas nocturnal hypertension was associated with male sex, smoking, and increased urinary albumin excretion. In treated patients, it was also associated with the presence of diabetes. Nondipping is related to more advanced disease (reduced renal function and clinical evidence of cardiovascular disease), whereas nocturnal hypertension is associated with albuminuria. The worst cardiovascular risk profile is present in patients exhibiting both nocturnal hypertension and nondipping.

AB0216 Activation of the renin angiotensin sistem in a population of patients with rheumatoid arthritis and low severity comorbidity in therapy with dmards and/or anti-tnf alfha

BackgroundRheumatoid arthritis(RA) is a chronic autoimmune inflammatory disease. The inflammatory process causes joint destruction and disability. Patients have a shorter life expectancy and a relative risk of cardiovascular (CV) disease...

Organ Damage in HIV-Positive Patients with High Blood Pressure

Our objective has been the investigation of possible cardiovascular or renal organ damage in HIV patients with confirmed high blood pressure by means of instrumental cardiovascular investigation and renal function evaluation. A total of 265 consecutive patients accessing our outpatient facility were enrolled in the study. Patients with confirmed pathological pressure values or high normal values were submitted to clinical and instrumental monitoring by 24-hour ambulatory blood pressure monitoring (ABPM), to derivation of 12-lead ECG registration, to echocardiography and to epi-aortic vessel echo-color-Doppler. The ECG and echocardiographic data were compared to a control group of 40 hypertensive HIV-negative subjects. Renal damage was evaluated by means of the microalbuminuria/creatininuria ratio on a spot urine sample, plus 24-hour albuminuria and proteinuria measurements. 61 (23.0%) of the subjects examined were hypertensive: 24 (39.3%) had a previous hypertensive diagnosis but had never been treated for this condition, and 37 (60.7%) had a new diagnosis; In 100% of cases, 24-hour ABPM confirmed the hypertension and 27.8% of the patients resulted non-dippers. The ECG showed left ventricle overload, V4-V6 strain, or left ventricular hypertrophy in 64.3% of cases compared to 35.7% in the control group. Echocardiography demonstrated increasing in left ventricle parietal thickness with concentric remodeling and hypertrophy in 85.2% of patients. HIV-positive patients showed a statistically significant tendency to concentric remodeling and concentric hypertrophy, even in presence of mild hypertension. Echocolor-Doppler examination detected intima-media thickness > and/or carotid plaques in 72.1% of patients. Renal function seems spared in these subjects. Our data highlights the importance of investigating arterial hypertension among our patients as it is a frequently undiagnosed condition, and illustrates the utility of 24- hr ABPM to confirm hypertension and to identify the non-dipper subject. Moreover, the ECG, echocardiography and echocolor-Doppler examinations evidenced a premature tendency to organ damage in these patients that showed altered cardiac remodeling compared to those without HIV. This stresses the need for an early diagnosis, including a complete instrumental evaluation to properly identify organ damage even at a subclinical level.

Impact of Cardiovascular Organ Damage on Cortical Renal Perfusion in Patients with Chronic Renal Failure

Introduction. Properly preserved renal perfusion is the basic determinant of oxygenation, vitality, nutrition, and organ function and its structure. Perfusion disorders are functional changes and are ahead of the appearance of biochemical markers of organ damage. The aim of this study was to evaluate a relationship between the renal cortex perfusion and markers of cardiovascular organ damage in patients with stable chronic renal failure (CKD). Methods. Seventeen patients (2 F; 15 M; age 47 ± 16) with stable CKD at 2–4 stages and hypertension or signs of heart failure were enrolled in this study. Blood tests with an estimation of renal and cardiac functions, echocardiographic parameters, intima-media thickness (IMT), renal resistance index (RRI), and total (TPI), proximal (PPI), and distal (DPI) renal cortical perfusion intensity measurements were collected. Results. DPI was significantly lower than PPI. TPI significantly correlated with age, Cys, CKD-EPI (cystatin), and IMT, whereas DPI significantly depended on Cystain, CKD-EPI (cystatin; cystatin-creatinine), IMT, NT-proBNP, and troponin I. In multiple stepwise regression analysis model only CKD-EPI (cystatin) independently influenced DPI. Conclusions. Cardiovascular and kidney damage significantly influences renal cortical perfusion. Ultrasound measurement of renal perfusion could be a sensitive method for early investigation of cardiovascular and renal injuries.

Shooting beyond score

ypertension is a complex disease, in whichelevated blood pressure reflects the impairmentof several regulatory and contraregulatory mech-anisms and systems. This, in turn, may lead to developmentandprogressionofasymptomaticsubclinicalorgandamage,hence promoting cardiovascular and renal diseases.During the long natural history of hypertensive disease,the presence of hypertension-related organ damage atcardiac, vascular and renal level has been demonstratedto largely and substantially impact prognosis in terms ofincreased incidence of cardiovascular and renal outcomesin large clinical trials. In turn, evidence derived from rela-tively smaller clinical studies or predefined analyses fromrandomized clinical trials have demonstrated that preven-tion, delayed progression or even regression of organdamageduringchronicantihypertensivetherapymaytrans-late into significant cardiovascular benefits.A paradigmatic example, is provided by the LosartanInterventionForEndpointreductioninhypertensiontrialinwhichthepresenceofleftventricularhypertrophy(LVH)ormicroalbuminuria(MAU)orbothatbaselinewasassociatedwith a significant increased risk of developing the primarycomposite endpoint (myocardial infarction, stroke andcardiovascular mortality) and mostly stroke during thefollow-up [1,2]. This increased risk was also largely inde-pendentofhoworgandamagewasassessed(electrocardio-graphic-LVH criteria with or without ST-segment strain orechocardiographic criteria for LVH) and it was not strictlyrelated to the concomitant treatments or blood pressurechanges during the study. In the same study, regression ofLVH [3,4] or MAU [5] was paralleled by a progressive,persistent and significant reduction of the risk ofcardiovascular outcomes. Other studies have linkedregression of LVH to cardiovascular benefits in hyperten-sion [6–9].Giventheimportanceofthepresenceand,mostly,ofthedevelopment of hypertension-related organ damage in theclinicalmanagementofhypertension, itisquitedisappoint-ing that no major attempt has yet been made to considermarkers of hypertension-related organ damage in moderntools and charts for cardiovascular risk assessment andevaluation developed and adopted in the US (FraminghamScore) or European [10] countries. The only risk algorithmthat has systematically taken into consideration the pres-ence/absence of organ damage in the definition of esti-mated added cardiovascular risk is represented by theEuropean Society of Hypertension/European Society ofCardiology (ESH/ESC) guidelines [11,12].Inclusion of markers of organ damage to risk charts orcalculators is feasible and can be done at low cost, especi-ally when the least expensive parameters (electrocardio-graphic-LVH, MAU, estimatedglomerular filtrationrate)areused. This may translate in improved cardiovascular riskstratification and more precise prognosis especially inintermediate-to-high risk patients. So, it is probably timeto take advantage from this and focus more on theseintermediate disease markers in risk charts applied tohypertensives.In this latter regard, Sehestedt et al. [13] in a previousstudy were able to demonstrate that in an apparentlyhealthy population, subclinical organ damages, as well asthe number of abnormal parameters indicating subclinicalorgan damage, were associated with increased cardiovas-cular risk, independently of Systematic COronary RiskEvaluation (SCORE). Combining the risk models of SCOREand subclinical organ damage yielded greater performanceon risk stratification and derived recommendations forprimary prevention. This approach allows reclassificationof the cardiovascular risk as defined by SCORE by simplyadding LVH and MAU. For example, in patients with aSCORE of 5% or more, the cardiovascular risk would bedoubled when taking into account the presence of any ofthese two markers of organ damage. At the same time, inpatients with a SCORE less than 5%, the presence of LVHalmost doubles the cardiovascular risk, whereas thepresence of MAU increases cardiovascular risk by morethan three-fold compared with those without MAU. Thiswas consistent with former Italian studies showing thatidentification of subclinical organ damage reclassify therisk profile of hypertensive patients [14].Anewanalysisperformedbythesamegroup[15],whichis published in this issue of the Journal, assessed the

A Systematic Review of Randomized Controlled Trials Examining the Nephroprotective Properties of Antihypertensive Medications

Introduction: Despite improved control rates of hypertension in the United States during the last thirty years, the rate of chronic kidney disease and end-stage renal disease has not demonstrated a similar resultant improvement. Purpose: The purpose for this review is to determine interventions in the treatment of hypertension that improve outcomes in the promotion of nephroprotection. Method: A systematic comprehensive search of the National Library of Medicine utilizing Medline was conducted with search limits confined to randomized controlled trials. Results: Angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are nephroprotective alone and in combination with other classes of antihypertensive agents, but can result in renal dysfunction when used in combination with each other or with a direct renin inhibitor (DRI). Older L-type calcium channel blockers (CCBs) can be nephrotoxic when used as monotherapy. CCBs are additionally nephroprotective when combined with ACEIs or ARBs. Thiazide-type diuretics (TTDs) with the exception of indapamide are not nephroprotective and TTDs may have nephrotoxic properties. Conclusion: ACEIs and ARBs are preferred first-line agents because they are effective in the prevention of renal as well as cardiovascular and cerebrovascular target organ damage associated with hypertension. CCBs are preferred when a second medication is needed for hypertension control. When diuretic therapy is indicated for hypertension control, indapamide is preferred over other TTDs for nephroprotection. Keywords: Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antihypertensive medications, calcium channel blockers, diuretics, hypertension, nephroprotection, renoprotection, combination therapy, nephropathy, Glomerular hypertension.

Ambulatory Blood Pressure Monitoring in Pediatric Renal Transplantation

Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and adverse cardiovascular outcomes. Blood pressure (BP) in transplanted children should be measured not only by clinic BP (cBP) measurement, but also by ambulatory blood pressure monitoring (ABPM), because ABPM has distinct advantages over cBP, specifically the ability to reveal nocturnal, masked or white-coat hypertension. These types of hypertension are common in transplanted children (nocturnal hypertension 36-71 %, masked hypertension 24-45 %). It may also reveal uncontrolled hypertension in treated children, thereby improving control of hypertension. Regular use of ABPM and ABPM-guided therapy of hypertension may help to decrease cardiovascular and renal target organ damage in transplanted children. Therefore, ABPM should be routinely performed in all transplanted children at least once a year, regardless of the values of cBP.

732 OXIDIZED-LDL-CHOLESTEROL EVALUATIONS IS USEFUL PARAMETER TO ESTIMATE ORGAN DAMAGE IN THE EARLY STAGE OF HYPERTENSION - SUB-ANALYSIS WITH ESTIMATED GFR - EIICHI GESHI. INTERNAL MEDICINE, SHOWA UNIVERSITY, YOKOHAMA, JAPAN

Objective: Oxidized-LDL-cholesterol has been considered as the upper stream of pathogenesis for atherosclerosis and following cardiovascular complications. Recently malondialdehyde-LDL (MDA-LDL) has been able to measure as oxidized-LDL and usefulness of MDA-LDL to estimate cardiovascular events. On the other hand, chronic kidney disease (CKD) is evaluated as a risk for cardiovascular damages. We evaluated MDA-LDL level in health-examination subjects with/without hypertension (HT) with sub-analyzed according to the eGFR. Design and method: In the subject of health-examination without any cardiovascular events (n = 283, (M: 135, F: 148), mean ages: 45.7 yrs), after informed-consents, they were divided into with/without HT. Furthermore, they were divided into 3 groups according to eGFR (high (H) eGFR >/ = 90 mL/min/1.73m+2, 90>medium (M) eGFR >/= 60, 60>low (L) eGFR). Then in each group, serum MDA-LDA and other cardiovascular events related factors were evaluated. Results: Mean systolic BP were 118.2 mmHg in HT(-) and 146.4 mmHg in HT(+), respectively. MDA-LDL was significantly higher in hypertension (HT(+);111.7IU/L (n = 53), HT(-); 96.6, (n = 230), p < 0.01), and it was correlated with Apo-B (p < 0.01) and RLP-C (p < 0.05), significantly. Furthermore, MDA-LDL was significantly inverse correlated (p < 0.01) with eGFR and it was 133.0IU/L in L-eGFR, 104.2 in M-eGFR, and 99.0 in H-eGFR, in HT group respectively, and hsCRP and NT-PRO-BNP were also inverse collated to eGFR. These significant differences in eGFR were similar in HT(-) group. Conclusions: MDA-LDL was significantly higher in hypertension without any cardiovascular complication and it was useful parameter to estimate potential cardiovascular organ damage in the early stage of hypertension especially with CKD.

AAV-Based RNAi Silencing of NADPH Oxidase gp91phox Attenuates Cold-Induced Cardiovascular Dysfunction

Clinical observations and epidemiological surveys indicated that the prevalence of hypertension and heart diseases is increased in cold regions or during winter. Cold exposure increased NADPH oxidase gp91(phox) protein expression in heart, kidneys, and aorta in rats. The aim of this study was to investigate if RNA interference (RNAi) silencing of gp91(phox) would attenuate cold-induced hypertension and cardiovascular and renal damage. The recombinant adeno-associated virus serotype 2 (AAV-2) vector carrying gp91(phox)-shRNA (gp91-shRNA) was constructed for inhibiting gp91(phox) protein expression in cold-exposed rats. Blood pressure (BP) was monitored using a telemetry system. BP was increased in the Control-shRNA and PBS groups within 1 week of exposure to moderate cold (5°C) and reached a plateau after 7 weeks. The cold-induced increase in BP was attenuated significantly by intravenous delivery of gp91-shRNA (1.25×10(10) particles/rat, 0.5 mL). One single dose of gp91-shRNA controlled hypertension for up to 10 weeks. In addition, gp91-shRNA reversed cold-induced vascular dysfunction. gp91-shRNA abolished the cold-induced up-regulation of gp91(phox) protein expression in heart, kidneys, and aorta, confirming effective silencing of gp91(phox). The cold-induced increases in NADPH oxidase activity and superoxide production were eliminated by silencing of gp91(phox), suggesting that the cold-induced up-regulation of NADPH oxidase activity may be attributed to the increased gp91(phox) protein expression. RNAi silencing of gp91(phox) abolished cold-induced cardiac and renal hypertrophy and attenuated aortic, coronary, and renal remodeling. The up-regulation of gp91(phox) may play a critical role in cold-induced cardiovascular dysfunction and organ damage. AAV delivery of gp91-shRNA may be a new and effective therapeutic approach for cold-related cardiovascular disorders.

Primary Aldosteronism in a Patient Who Exhibited Heart Failure

Primary aldosteronism (PA) is a common cause of secondary hypertension due to unilateral adrenocortical adenoma (APA) or idiopathic hyperplasia. There is increased awareness of the possible cardiac sequelae of aldosterone excess, including cardiac hypertrophy, fibrosis, and vascular endothelium injury. A 54-year-old woman was referred for rest and nighttime worsening dyspnea and palpitations. One year earlier she was admitted to another hospital with the same symptoms and discharged with a diagnosis of idiopathic dilated cardiomiopathy. At admission, physical examination revealed a body mass index of 21 kg ⁄m and blood pressure (BP) of 210 ⁄105 mm Hg. Chest auscultation revealed mild expiratory wheezes and rales in both lower lobes. Electrocardiography showed signs of left ventricular (LV) overloading and hypertrophy. Laboratory analysis showed severe hypokalemia (1.8 mEq ⁄L; normal range 3.5–5 mEq ⁄L) and metabolic alkalosis (pH 7.51; partial pressure of carbon dioxide 41 mm Hg; partial pressure of oxygen 86 mm Hg; HCO 3 32.6 mmol ⁄L; excess bases 10 mmol ⁄L) (Table I). Chest radiography revealed an enlarged cardiac silhouette, congested pulmonary hilum, and bilateral pleural effusion (Figure 1A). Echocardiography showed an increase in LV end-diastolic diameter (58 mm) and left atrial volume (46 mm) and a signficant decrease in global LV performance (ejection fraction [EF] 30%) (Table II). The 24hour ambulatory BP monitoring (ABPM) revealed severe systo-diastolic hypertension without physiological nocturnal fall (nondipper pattern). Subsequent investigation showed suppressed plasma renin activity (PRA) (0.08 ng ⁄mL ⁄h; normal range 0.2–2.7 ng ⁄mL ⁄h), high plasma aldosterone (PAC 16.17 ng ⁄dL; normal range 7.5–15 ng ⁄dL), and PAC ⁄ PRA ratio (202.17 ng ⁄dL: ng ⁄ml ⁄h; normal value<30 ng ⁄dL: ng ⁄mL ⁄h). Because of suspicion of PA, we performed a captopril test. After 60 minutes of captopril 50 mg, the PAC ⁄PRA ratio was still elevated (529.93 ng ⁄dL: ng ⁄mL ⁄h). Magnetic resonance imaging of the superior abdomen demonstrated a 20-mm nodule in the left adrenal gland (Figure 2). The patient underwent laparoscopy adrenalectomy, and histopathology revealed an APA. Subsequently, her BP was normalized at 140 ⁄90 mm Hg with amlodipine, ramipril, and serum potassium. After 6 months of follow-up, BP was 110 ⁄80 mm Hg, with normal serum potassium. Chest radiography showed resolution of congestive heart pulmonary imaging with a decreased cardiac silhouette (Figure 1B). Repeat echocardiography demonstrated a significant improvement in LV hypertrophy and EF (50%). Recently, the Primary Aldosteronism Prevalence in Italy Study (PAPY) reported a PA prevalence of 11.2% in patients with new-onset hypertension. The potential comorbidity and prevention of excessive cardiovascular events and organ damage led to development of accurate strategies for diagnosis of PA. PA patients display an unfavorable cardiovascular profile, suggesting a role of aldosterone beyond its well-known hypertensive effects. TABLE I. Laboratory Data and Blood Gas Analysis

Arterial hypertension and dyslipidemia in a HIV-positive patient treated with antiretroviral therapy

The introduction of antiretroviral therapy (ART) has substantially modified the clinical history and epidemiology of HIV infection with an important decline in infective causes of death and an increase in non-infective comorbidities particularly in cardiovascular complications. HIV infection has been related to an increased cardiovascular risk due to the presence of three factors: classic cardiovascular risk factors (shared with the general population), HIV infection itself (indirectly due to the inflammation and directly due to viral molecule) and ART-related chronic metabolic alterations. We describe a peculiar case of metabolic alteration in an HIV infected patient on ART with particular attention to the diagnosis and therapeutic aspects. Giving the higher cardiovascular risk of this specific population it is advisable that the clinician performs a frequent re-assessment of risk factors and cardiovascular organ damage. An early detection of metabolic alteration must lead to an aggressive specific therapy; this must be done by taking care of the HIV-infected subject fragility and the interactions with ART.

What are the real determinants of the ambulatory arterial stiffness index?

O ver the last few years, increasing attention has been devoted to the pathophysiological role of large arteries in functionally coupling the left ventricle with peripheral vessels [1]. Particularly, an increasing number of articles have focused on the investigation of the functional properties of the large arteries, through the availability of devices able to allow the noninvasive analysis of arterial pulse waveforms in normal conditions, as well as the assessment of their modifications in a number of diseases [2,3]. Making use of this approach, evidence has been provided that arterial stiffness, assessed through the quantification of aortic pulse–wave velocity (PWV), may be a predictor of cardiovascular organ damage as well as of cardiovascular events [4,5]. On the basis of such evidence, aortic PWV has been included among those factors influencing prognosis in hypertensive patients, the evaluation of which may allow a more precise assessment of cardiovascular risk [6]. In spite of its universally acknowledged pathophysiologic and clinical value, however, aortic PWV has not become yet a routine procedure to assess the level of cardiovascular risk of hypertensive patients in daily clinical practice. This is mainly due to the need of dedicated and often expensive equipment for its assessment, as well as to the requirement of careful training of the personnel in charge of its measurement. These difficulties have stimulated research and development of new technologies to estimate arterial stiffness in humans in an easier manner, based on the obvious consideration that a technique able to assess arterial wall properties, without the need of using specially designed and costly equipment and without the mandatory requirement of carefully trained and highly qualified observers,