Cardiovascular Damage In Patients Research Articles

Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy.

Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib. To assess the cardiovascular damage in patients treated with PI for RRMM. 28 consecutive subjects treated with PI for RRMM were evaluated and compared with a population of 22 control (Con) subjects, matched for age, sex and mean 24h blood pressure (24hMBP). All individuals underwent trans-thoracic echocardiography, ambulatory blood pressure monitoring and pulse wave velocity (PVW) study. PI patients did not have significant differences in blood pressure load and PWV compared to controls. Among echocardiographic parameters, the global longitudinal strain (GLS) was significantly decreased in PI subjects (p = 0.02). The GLS was significantly lower also considering only patients treated with carfilzomib. Moreover, among carfilzomib patients, we found increase values of left ventricle mass indexed by BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and morphological and functional parameters of LV, treatment with PI and carfilzomib were significantly associated with GLS (p = 0.01; p = 0.036, respectively). PI treatment is associated with subclinical LV dysfunction in patients with RRMM compared to controls, as demonstrated by lower GLS values. These results are confirmed also considering patients treated with carfilzomib. Moreover, in this subgroup of patients, the LVMi is also increased, suggesting higher cardiotoxicity with this treatment.

Vascular Endothelial Growth Factor Inhibitor Therapy and Cardiovascular and Renal Damage in Renal Cell Carcinoma.

Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment. Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), hemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001), IVS (p=0.03) and proteinuria (p<0.001), while we showed no significant differences in glycosuria, phosphaturia, serum uric acid, intact parathormone, and LVMI. We observed the development of renal damage and worsening of CV indices in patients treated with sunitinib. We suggest to consider a careful assessment of renal function and CV risk factors, before initiation and during administration of this drug.

Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity

Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m2. We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatitis [NASH] and fibrosis), insulin resistance, and diabetes. Overweight was defined as a BMI of 25 to 29.9 kg/m2, and obese was defined as a BMI of 30 kg/m2 or greater. Patients were assigned to groups based on waist circumference, a marker of visceral obesity (low: men, <94 cm, women <80 cm; medium: men, 94-102 cm, women 80-88 cm; or high: men >102 cm, women >88 cm). DNA samples were analyzed for the rs738409 C>G (I148M in PNPLA3), the rs58542926 C>T (E167K in TM6SF2), and single-nucleotide polymorphisms. Variables in men and women were analyzed using chi-squared analysis and the Mann-Whitney or Kruskal-Wallis tests. Multiple linear or logistic regression analyses were adjusted for all the variables of clinical relevance or statistically significant at univariate analyses. The primary outcome was the difference in liver and cardiovascular disease between lean NAFLD and NAFLD in overweight and obese persons. Secondary outcomes were effects of visceral obesity, based on waist circumference, on hepatic, vascular, and metabolic features. Significantly lower proportions of patients with lean NAFLD (143 patients; 43 women; mean age, 46 ± 13 y) had hypertension (P= .001), diabetes (P= .0001), and metabolic syndrome (P=.0001) than overweight or obese patients with NAFLD (526 patients; 149 women; mean age, 49 ± 12 y). Significantly lower proportions of patients with lean NAFLD had NASH (17% vs 40% of obese or overweight patients with NAFLD; P= .0001), fibrosis of F2 or higher (17% vs 42%; P=.0001), or carotid plaques (27% vs 39%; P= .03). Patients with lean NAFLD had significantly thinner carotid intima-media (0.74 ± 0.1 mm) than obese or overweight patients with NAFLD (0.84 ± 0.3 mm; P= .0001). There was no significant difference in the proportions of patients with rs738409 C>G in PNPLA3, but a significantly greater proportion of patients with lean NAFLD carried rs58542926 C>T in TM6SF2 (4%) than obese or overweight individuals with NAFLD (0.3%; P= .001). Of the 143 patients with lean NAFLD, 27 had grade 3 steatosis, 24 had a lobular inflammation score greater than 2, 10 had a ballooning score of 2, and 25 had a fibrosis score of 2 or higher. In patients with lean NAFLD, the only variable associated independently with NASH and a fibrosis score of 2 or higher was rs738409 C>G in PNPLA3. Patients with lean NAFLD and a medium waist circumference had a significantly higher risk of diabetes (odds ratio, 11; 95% confidence interval [CI], 1.2-106; P=.03) than overweight or obese patients with a similar waist circumference (odds ratio, 1.3; 95% CI, 0.4-4.2; P= .6). Lean and overweight or obese patients with high waist circumferences had significant increases in risk compared with patients with low and medium circumference and diabetes, hypertension, and fibrosis scores of 2 or higher. In a retrospective study of patients with lean NAFLD vs obese or overweight persons with NAFLD, we found 20% of patients with lean NAFLD to have NASH, fibrosis scores of 2 or higher, and carotid atherosclerosis. Lean patients with rs738409 C>G in PNPLA3 should be monitored for liver disease progression; studies including large series of patients with lean NAFLD will clarify the possible role of TM6SF2 polymorphisms.

Expression of thrombus regulatory protein and myeloperoxidasein peripheral blood of adult with obstructive sleep apnea hypopnea syndrome

Objective:To investigate the expression of serum TM and MPO in adult patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Method: Ninety OSAHS patients who confirmed by PSG as OSAHS group. According to AHI, the patients were divided into 3 groups include heavy, medium and light, and 30 healthy outpatients were control group. The serum TM and MPO were determined by ELISA; TM and MPO were measured after comprehensive treatment in patients with severe OSAHS, and the correlation between TM, MPO and PSG were analyzed. Result: ①With the severity of OSAHS patients increased, the serum levels of TM and MPO increased gradually（F=20.761,21.433；P<0.01). There was no significant difference about the concentration of TM and MPO between light and control group（P>0.05）；The concentration of TM and MPO was significantly higher in heavy and medium group compared with light and control group（P<0.01）.②There was no correlation between serum levels of TM, MPO, BMI, age and sex in OSAHS patients(P>0.05). The serum concentration of TM was positively related to MPO. The serum concentrations of TM and MPO were positively correlated with AHI, but negatively with LSaO₂ (P<0.05). ③LSaO₂ was significantly increased, AHI and peripheral blood TM, MPO levels were significantly reduced in thirty severe OSAHS cases received the combined treatment(P<0.01).Conclusion:The increase of TM and MPO concentration in peripheral blood is one of characteristics of cardiovascular damage in patients with OSAHS. Combined detection of serum TM and MPO concentrations in patients with the disease is helpful for evaluation and risk assessment of cardiovascular disease.

Biology of High-Density Lipoproteins: An Update49High density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kB/STAT1-IRF1 signaling50Homocysteine accelerated the formation of THP-1 macrophages-derived foam cells and cholesterol disorder via regulating the expressions of LXRa, ABCA1 and ABCG151Protein components of HDL as markers of cardiovascular damage in patients with arterial hypertension

Biology of High-Density Lipoproteins: An Update49High density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kB/STAT1-IRF1 signaling50Homocysteine accelerated the formation of THP-1 macrophages-derived foam cells and cholesterol disorder via regulating the expressions of LXRa, ABCA1 and ABCG151Protein components of HDL as markers of cardiovascular damage in patients with arterial hypertension

Vascular Damage in Patients with Nonalcoholic Fatty Liver Disease: Possible Role of Iron and Ferritin.

Non Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease in Western countries. Recent data indicated that NAFLD is a risk factor by itself contributing to the development of cardiovascular disease independently of classical known risk factors. Hyperferritinemia and mild increased iron stores are frequently observed in patients with NAFLD and several mechanisms have been proposed to explain the role of iron, through oxidative stress and interaction with insulin metabolism, in the development of vascular damage. Moreover, iron depletion has been shown to decrease atherogenesis in experimental models and in humans. This review presents the recent evidence on epidemiology, pathogenesis, and the possible explanation of the role of iron and ferritin in the development of cardiovascular damage in patients with NAFLD, and discusses the possible interplay between metabolic disorders associated with NAFLD and iron in the development of cardiovascular disease.

How does serum brain natriuretic peptide level change under nasal continuous positive airway pressure in obstructive sleep apnea-hypopnea syndrome?

BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with cardiovascular morbidity and mortality, which can be improved by using continuous positive airway pressure (CPAP) therapy. However, the pathophysiological links between the two kinds of disease and the mechanism of the CPAP effect remain incompletely understood. We aimed to inquire into the myocardial involvement in this relationship. We suggested that serum brain natriuretic peptide (BNP) is sensitive enough to detect myocardial stress caused by OSAHS.Design and methodsSixty-four subjects without cardiovascular disease (21 controls, 24 normotensive OSAHS patients, and 19 hypertensive OSAHS patients) were analyzed for serum BNP at baseline and serially over 6 months. CPAP was applied to 23 patients with severe OSAHS.ResultsAt baseline, the serum BNP levels were significantly higher (p=0.0001) in the OSAHS group (22.3±14.79 pg/ml) than in the control group (9.2±6.75 pg/ml). Increased serum BNP levels were significantly associated with mean transcutaneous oxygen saturation (SpO2) (p<0.0001), minimal SpO2 (p=0.002), oxygen desaturation index (p=0.001), and total sleep time spent with SpO2 lower than 90% (p=0.002). All patients with elevated BNP levels (≥37 pg/ml) had moderate or severe OSAHS (11/43 OSAHS patients). The more severe the OSAHS, the higher the BNP levels were. However, only the difference between severe and mild OSAHS was statistically significant (p=0.029). Hypertensive OSAHS patients had the highest baseline BNP levels (27.7±16.74 pg/ml). They were significantly higher (p=0.001) than in normotensive OSAHS patients (18±11.72 pg/ml) (p=0.039) and the controls (9.2±6.75 pg/ml). As compared with baseline, treatment with CPAP significantly decreased BNP levels in both hypertensive and normotensive OSAHS patients (respectively, from 36±16.10 to 29.7±14.29 pg/ml, p<0.001, and from 20±10.09 to 16±8.98 pg/ml, p<0.001). In contrast, the BNP levels slightly increased in the controls (from 9.2±6.75 to 9.5±7.02 pg/ml, p=0.029), but there was no statistically significant difference in comparison with the baseline value. The effect of CPAP on BNP levels was more marked in patients with higher baseline BNP levels and those with the most prolonged nocturnal desaturation (p=0.001, r=0.65). It was also more marked in hypertensive OSHAS patients (p=0.015, r=0.72) in comparison with normotensive OSAHS patients (p=0.03, r=0.62).ConclusionBNP seems to be sensitive enough to detect myocardial stress caused by OSAHS. As such, it is a potential marker for screening of preclinical cardiovascular damage in patients with untreated OSAHS. Application of CPAP decreases levels significantly in normotensive and particularly in hypertensive OSAHS. These findings are consistent with previous results suggesting the potential benefits of CPAP on cardiovascular outcome in OSAHS patients.

PP.18.21

Objective: Radiotherapy (RT) of thoracic cancers exposes to late radiation induced complications, strengthened from pre-existing cardiovascular risk factors. The heart post-RT damage is a well known phenomenon and conformational RT has allowed its drastic reduction. However, prolonged life expectancy of cancer patients underlines the need to evaluate cardio-vascular risk for many years after therapy, also in attempt to prevent the increase cardiovascular mortality that it has been recently proposed in radio-treated subjects. An arterial structural or functional damage induced by RT might be one of mechanisms for increased atherosclerotic process in these subjects. Aim of our study was to evaluate arterial function by means of PWV and Aix in subjects treated by chest radiotherapy. Design and method: We enrolled 42 patients treated with radiotherapy 15 years ago for Mammary Cancer. We assessed traditional risk factors, atherosclerotic organ damage (Carotid Ultrasound) and functional arteries evaluation with carotid-radial PWV (Complior) and AIx (Sphygmocor). We divided patients in R (N = 26) (therapy on right mammary gland), and L (N = 18) (left mammary gland). Results: None of patients had story of cardiac artery disease. R and L had similar ages (70 ± 8vs68 ± 8 yrs,means+SD), BSA (1.68 ± 0.16vs1.7 ± 0.12 m2), distribution of hypercholesterolemia (40vs39%) and active smoking (8vs7%). R had higher prevalence of hypertension (60vs57%), instead L of diabetes (17vs12%). IMT was more frequently increased (>0.9 mm) in R than in L (38vs33%). R had a significantly increased cr-PWV on right arm compared with left arm (9.9 ± 1.4vs8.9 ± 1.2,p < 0.05); L had a significantly increased cr-PWV (9.5 ± 1.5vs9 ± 1.3,p < 0.05) and AIx on left arm (32.1 ± 7.6vs28.3 ± 6.8,p < 0.05). In both groups no significant differences were found on central blood pressure estimation between right and left arm. No correlations were found with hormone-therapy or chemotherapy. Conclusions: Our preliminary data suggest that arteries function reflects a possible local damage due to RT. This specific and local increased in arterial stiffness might be one of mechanisms under the increase atherosclerotic phenomenon and subsequent pathologies in RT patients. It could be useful to estimate the global cardio-vascular damage in patients subjected to chest radiotherapy and to access a complete cardio-vascular risk stratification in order to plan an optimized cardio-preventive strategy.

Association between sleep quality and cardiovascular damage in pre-dialysis patients with chronic kidney disease.

BackgroundPoor sleep quality, a novel risk factor of cardiovascular diseases (CVD), is highly prevalent in patients with chronic kidney disease (CKD). The association between poor sleep quality and cardiovascular damage in patients with CKD is unclear. This study is aimed to assess the prevalence and related risk factors of sleep disturbance and determine the relationship between sleep quality and cardiovascular damage in Chinese patients with pre-dialysis CKD.MethodsA total of 427 pre-dialysis CKD patients (mean age = 39 ± 15 years, 260 male/167 female) were recruited in this study. The demographics and clinical correlates were collected. The sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI), whereas the cardiovascular damage indicators (the Early/late diastolic peak flow velocity (E/A) ratio and left ventricular mass index (LVMI)) were determined by an echocardiographic examination.ResultsOf the CKD patients, 77.8% were poor sleepers as defined by a PSQI score > 5. Median estimated glomerular filtration rate (eGFR) was 69.4(15.8-110.9) ml/min/1.73 m2. Logistic regression analysis revealed that left ventricular hypertrophy (LVH) was independently associated with the PSQI score (OR = 1.092, 95% CI = 1.011-1.179, p = 0.025), after adjustment for age, sex and clinical systolic blood pressure, diastolic blood pressure, Phosphate, Intact parathyroid hormone (iPTH), Hemoglobin and eGFR. The linear regression analysis showed that the E/A ratios were independently associated with the PSQI score (β = -0.115, P = 0.028) after adjustment for a series of potential confounding factors.ConclusionsPoor sleep quality, which is commonly found in pre-dialysis CKD patients, is an independent factor associated with cardiovascular damage in CKD patients. Our finding implies that the association between poor sleep and CVD might be mediated by cardiac remodeling.

Reversed Dipper Blood-Pressure Pattern Is Closely Related to Severe Renal and Cardiovascular Damage in Patients with Chronic Kidney Disease

BackgroundA non-dipper blood pressure (BP) pattern is very common in chronic kidney disease (CKD) patients and affects the progression and development of cardiovascular disease. However, data on the reversed dipper BP pattern on target-organ damage in Chinese CKD patients are lacking.MethodsA total of 540 CKD patients were enrolled. Ambulatory blood pressure monitoring (ABPM), clinical BP, ultrasonographic assessment and other clinical data were collected. Univariate and multivariate analyses were used to ascertain the relationship between ABPM results and clinical parameters.ResultsA total of 21.9% CKD patients had a reversed dipper BP pattern, 42% of patients had a non-dipper BP pattern and 36.1% of patients had a dipper BP pattern. Patients with reversed dipper BP pattern had the worst renal function and most severe cardiovascular damages among these CKD patients (p<0.05). The estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) correlated significantly with the rate of decline of nocturnal BP. A reversed dipper BP pattern was an independent factor affecting kidney damage and left ventricular hypertrophy. Age, lower hemoglobin level, higher 24-h systolic BP from ABPM, and higher serum phosphate levels were independent associated with a reversed dipper BP pattern after multivariate logistic regression analyses.ConclusionThe reversed dipper BP pattern is closely related to severe renal damage and cardiovascular injuries in CKD patients, and special attention should be given to these CKD patients.

Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease

Animal and human studies support a clinically relevant interaction between aldosterone and parathyroid hormone (PTH) levels and suggest an impact of the interaction on cardiovascular (CV) health. This review focuses on mechanisms behind the bidirectional interactions between aldosterone and PTH and their potential impact on the CV system. There is evidence that PTH increases the secretion of aldosterone from the adrenals directly as well as indirectly by activating the renin-angiotensin system. Upregulation of aldosterone synthesis might contribute to the higher risk of arterial hypertension and of CV damage in patients with primary hyperparathyroidism. Furthermore, parathyroidectomy is followed by decreased blood pressure levels and reduced CV morbidity as well as lower renin and aldosterone levels. In chronic heart failure, the aldosterone activity is inappropriately elevated, causing salt retention; it has been argued that the resulting calcium wasting causes secondary hyperparathyroidism. The ensuing intracellular calcium overload and oxidative stress, caused by PTH and amplified by the relative aldosterone excess, may increase the risk of CV events. In the setting of primary aldosteronism, renal and faecal calcium loss triggers increased PTH secretion which in turn aggravates aldosterone secretion and CV damage. This sequence explains why adrenalectomy and blockade of the mineralocorticoid receptor tend to decrease PTH levels in patients with primary aldosteronism. In view of the reciprocal interaction between aldosterone and PTH and the potentially ensuing CV damage, studies are urgently needed to evaluate diagnostic and therapeutic strategies addressing the interaction between the two hormones.

Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus

The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44°C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (≥5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients.

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort

To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration <or=5 years at baseline (T0), of African-American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean +/- S.D. total disease duration of 6.6 +/- 3.6 years. Nearly 90% of the patients were women with a mean +/- s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94). Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.

Low triiodothyronine and cardiomyopathy in patients with end-stage renal disease

Low free plasma triiodothyronine (fT3) is associated with inflammation and cardiovascular damage in patients with end-stage renal disease (ESRD). We investigated the relationship between fT3, left ventricular systolic function and left ventricular mass in a group of 234 dialysis patients, and modelled the association between fT3 and cardiomyopathy in statistical analyses including both direct (interleukin-6 and C-reactive protein) and inverse (serum albumin) acute phase inflammation markers. Plasma fT3 concentration in dialysis patients was significantly (P < 0.001) reduced in comparison with healthy participants and clinically euthyroid patients with normal renal function. Left ventricular systolic function was depressed (P <or= 0.003) and left ventricular mass increased (P < 0.001) in patients in the first fT3 quartile as compared with patients in other quartiles. In multiple regression analyses these associations remained significant also after adjustment for Framingham risk factors and antihypertensive therapy (P </= 0.01), and for risk factors peculiar to ESRD (P = 0.03). Adjustments for interleukin-6 or for albumin, however, abrogated these relationships. Low triiodothyronine is associated with left ventricular dysfunction and left ventricular hypertrophy in ESRD patients. These associations appear largely mediated by inflammation. Low fT3 may be an intermediate mechanism implicated in the adverse cardiac effects of inflammation in patients with ESRD.

Patients with Cushing’s Syndrome Have Increased Intimal Media Thickness at Different Vascular Levels: Comparison with a Population Matched for Similar Cardiovascular Risk Factors

Cushing's syndrome (CS) is associated with high cardiovascular risk. The aim of this study was to analyze intimal media thickness (IMT) in patients with CS and compare them with subjects matched for similar conventional and independent cardiovascular risk factors. Twenty eight patients with CS (mean age: 40.7 +/- 2.5 y) and 28 subjects (mean age: 41.1 +/- 14 y) matched for sex, age, smoking habit, body mass index, blood pressure levels, glucose and lipid metabolism were evaluated. IMT was measured at right and left common carotid (CC), carotid bulb (BC), aorta (Ao) and femoral (F) levels by B-echo-Doppler ultrasonography. Although parameters of cardiovascular risk factors did not differ statistically between patients and controls, IMT was significantly increased (right and left CC-IMT, p < 0.05; right and left BC-IMT, p < 0.01, Ao-IMT p < 0.05) and wall plaques were more common (14.2 % VS. 7.1 %) in patients. In CS patients, CC-IMT and F-IMT correlated positively and significantly with fasting glucose (right CC-IMT: r (2) = 0.37, p = 0.05; left CC-IMT: r (2) = 0.43, p = 0.02; right F-IMT: r (2) = 0.57; p < 0.01; left F-IMT: r (2) = 0.47, p = 0.01) and HOMA index (left CC-IMT: r (2) = 0.64, p < 0.01 and left F-IMT: r (2) = 0.48, p < 0.05). The CS patients' waist-to-hip ratio (WHR) was evaluated and correlated positively and significantly with CC-IMT (right: r (2) = 0.53, p = 0.01 and left: r (2) = 0.44, p = 0.05). No correlation was found between IMT and cortisol levels, however. In conclusion, patients with CS have more severe atherosclerotic damage than a population matched for similar cardiovascular risk factors. Multiple events related to long-term cortisol effects on metabolism and at vascular and endothelial sites may increase the risk of cardiovascular damage in patients with CS.

Low parathyroid hormone and pentosidine in hemodialysis patients

Background: Accumulation of advanced glycation end products (AGEs) has been linked to the severity of osteoarticular and cardiovascular damage in patients with end-stage renal disease. Methods: We studied the relationship between plasma pentosidine and parathyroid hormone (PTH) levels and bone turnover in a group of hemodialysis patients (n = 85) with minimal aluminum exposure. Results: Plasma pentosidine levels were greater than the upper limit of normal range (cutoff value, 2.46 pmol/mg protein) in all dialysis patients. When patients were divided into three tertiles according to plasma pentosidine levels, serum PTH levels were approximately six times lower in patients in the third pentosidine tertile than in those in the first tertile (P = 0.008), and a similar association (P = 0.009) was found between pentosidine and bone alkaline phosphatase levels. Multivariate analysis confirmed that these relationships were independent of established risk factors for low bone turnover. Forty patients (47%) had serum PTH levels less than 125 pg/mL (13.2 pmol/L). Of note, in a multiple logistic regression model, the relative risk for low PTH level was 4.02 (95% confidence interval, 1.30 to 12.40; P = 0.02) times greater in patients in the third pentosidine tertile than in the first tertile. Conclusion: Pentosidine, a reliable indicator of AGEs, is related inversely to circulating PTH and bone alkaline phosphatase levels. These associations are in agreement with recent experimental data indicating that AGE accumulation may be a factor involved in low bone turnover in dialysis patients. © 2002 by the National Kidney Foundation, Inc.

Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients

We prospectively tested the prediction power of homocysteinemia for all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients followed for 29 +/- 12 months. Survival analysis was performed by the Cox's proportional hazard model and data were expressed as hazard ratio and 95% confidence interval (CI). During the follow-up period 51 patients died, 31 of them (61%) of cardiovascular causes and 16 patients developed non-fatal atherothrombotic complications. Plasma total homocysteine was an independent predictor of cardiovascular mortality (P=0.01). Combined analysis of fatal and non-fatal atherothrombotic events showed that homocysteine was a strong and independent predictor of these outcomes because the risk of these events was 8.2 times higher (95% CI 1.9 to 32.2) in patients in the third homocysteine tertile than in those in the first tertile (P=0.005). There is a clear association between hyperhomocysteinemia and incident cardiovascular mortality and atherothrombotic events in hemodialysis patients. Intervention studies are needed to determine whether the accumulation of this substance has a causal role in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis.

Importance of Smooth and Sustained Blood Pressure Control in Preventing Cardiovascular Morbidity and Mortality

Current management guidelines in hypertension define the magnitude of blood pressure lowering required from antihypertensive therapy to favourably alter cardiovascular prognosis. In addition, however, the manner in which blood pressure is reduced also influences outcome, and antihypertensive therapy should induce smooth and sustained blood pressure control throughout the 24-h dosing interval. Ambulatory blood pressure recording techniques, in particular, have allowed the quantitative measurement of parameters such as the short-term variability of blood pressure, which correlates significantly with cardiovascular damage in patients with hypertension. The smoothness index has been developed as an index of the homogeneity of the blood pressure reduction obtained over the 24 hours by any given treatment during a long-term trial in patients with hypertension. This parameter is more predictive of a favourable effect of antihypertensive therapy (regression of left ventricular hypertrophy) during antihypertensive therapy than the widely used trough:peak ratio. The smoothness index is a useful new tool for comparing the quality of blood pressure lowering with different antihypertensive agents. For example, candesartan cilexetil, a potent and long-acting AT 1 -receptor blocker, increased the smoothness index by a significantly greater extent than the prototype AT 1 -receptor blocker, losartan, implying a more smooth and sustained antihypertensive effect.

Hypertensive cardiovascular damage in patients with primary autonomic failure

Patients with primary autonomic failure have left-ventricular hypertrophy probably as a result of night-time hypertension.

Echocardiographic Detection of Left Ventricular Hypertrophy: Its Usefulness as a Prognostic Tool in Hypertensive Patients

There is strong evidence that in hypertensive patients, electrocardiographic findings of left ventricular hypertrophy (LVH) are associated with a poor cardiovascular prognosis. In the Framingham study, the presence of defined electrocardiographic evidence of LVH was found to be associated with an increased likelihood of major cardiovascular events, independent of blood pressure level. 1 Kannel WB Gordon T Offutt D Left ventricular hypertrophy by electrocardiogram: prevalence, incidence and mortality in the Framingham study. Ann Intern Med. 1969; 71: 89-105 Crossref PubMed Scopus (692) Google Scholar , 2 Kannel WB The Framingham study. Am J Med. 1983; 75: 4 Abstract Full Text PDF PubMed Scopus (350) Google Scholar Since the detection of such target organ damage is critical for the clinical management of hypertensive patients, an accurate identification of abnormal cardiac anatomy seems particularly important. Although the electrocardiogram (ECG) has been the conventional clinical diagnostic tool for the detection and assessment of acute ischemia, conduction abnormalities, and rhythm disturbances, it has not been highly sensitive in the detection of changes in cardiac mass such as LVH. In a large-scale study by Savage et al 3 Savage DD Drayer JIM Henry WL Mathews Jr, EC Ware JH Gardin JM et al. Echocardiographic assessment of cardiac anatomy and function in hypertensive subjects. Circulation. 1979; 59: 623-632 Crossref PubMed Scopus (342) Google Scholar of patients with mild to moderate hypertension, the ECG and the chest x-ray film each identified approximately 5 percent of the patients as having met the classic criteria for a diagnosis of LVH, whereas echocardiographic criteria for LVH were demonstrated in almost 50 percent. Echocardiography, therefore, might represent the first truly sensitive and widely available noninvasive diagnostic method for critically evaluating early evidence of cardiovascular damage in patients with mild to moderate hypertension. 4 Devereux RB Alonso DR Lutas EM Gottlieb GJ Campo E Sachs I et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986; 57: 450-458 Abstract Full Text PDF PubMed Scopus (5583) Google Scholar This technique may potentially be of value in determining which patients will benefit most from long-term antihypertensive therapy, as well as in evaluating the effect of long-term antihypertensive therapy on left ventricular mass in patients with essential hypertension. So far, only a few long-term follow-up clinical trials have been reported. Therefore, there has not been sufficient time nor clinical experience as yet to evaluate definitively the prognostic significance of echocardiographic evidence for LVH or the use of antihypertensive therapy to reduce LVH, especially in those patients whose ECG and chest roentgenograms are apparently normal. 5 Weber MA Drayer JIM Baird WM Echocardiographic evaluation of left ventricular hypertrophy. J Cardiovasc Pharmacol. 1986; 8: S61-S68 Crossref PubMed Scopus (15) Google Scholar