Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.

PURPOSE: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. METHODS: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. RESULTS: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). CONCLUSION: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

The diverse roles of adiponectin in non-small-cell lung cancer: current data and future perspectives.

In recent years, there is growing research interest for the biological role of adipose tissue-derived bioactive factors, mainly including adipokines, in various forms of cancer. Adiponectin (APN) is the most abundant circulating adipokine, and a key mediator of several cancer-related processes, such as cell proliferation, apoptosis, regulation of tumor cell invasion and angiogenesis. In this review we summarize and critically discuss the published literature on the diverse roles of APN in non-small-cell lung cancer, including its implication in lung cancer development, its use as a diagnostic and prognostic biomarker, and its correlation with cancer-related cachexia. The main challenges and future perspectives, mainly with regard to the potential development of APN-targeted therapeutic agents in cancer therapeutics, are also briefly presented and discussed.

Nitric oxide, ammonia, and CRP levels in cirrhotic patients with hepatic encephalopathy: is there a connection?

GOALS: Comparison of nitric oxide (NO) levels in cirrhotic patients with and without hepatic encephalopathy (HE), evaluation of possible correlation between HE and other clinical or laboratory characteristics, and estimation of utilization of NO levels in clinical practice. BACKGROUND: HE is a neuropsychiatric complication of cirrhosis. The exact pathogenetic mechanisms underlying the presence of HE are not known. However, dysfunction of the NO pathway and ammonia detoxification are thought to play a major role. STUDY: Sixty-seven cirrhotic patients, 36 (53.7%) without HE, and 31 (46.3%) with HE were included in the study. Eighteen healthy individuals were used as control group. Clinical and laboratory data, including ammonia and stable end products of NO using Griess reaction, were collected. RESULTS: NOx levels were statistically significantly higher in cirrhotic patients (225.5 µmol/L) than in control group [(67.94 µmol/L) (P=0.000)]. NOx levels were, also, statistically significantly higher in patients with HE compared with patients without HE (324.67 µmol/L vs. 141.96 µmol/L, P=0.000). Significant correlation between the presence of HE and NOx, ammonia, C-reactive protein, albumin, Model for End-Stage Liver Disease score, and Child-Pugh classification revealed. NOx levels also correlated with severity of HE. NOx and ammonia are independent factors predicting HE according to regression analysis. Diagnostic accuracy for the diagnosis of HE using a combination of NOx and ammonia was superior compared with standalone NOx or ammonia utilization. CONCLUSIONS: NOx levels are correlated with the presence and severity of HE. NOx levels determination, in addition to ammonia levels, could contribute in diagnosis of HE.

Perioperative SBP changes during orthopedic surgery in the elderly: clinical implications.

OBJECTIVES: We aimed to determine SBP changes during the perioperative period of a scheduled knee surgery under regional anesthesia and the extent of perioperative (in-hospital) white-coat effect. METHODS: All patients (aged ≥60 years) underwent clinic SBP measurements during both cardiological and anesthesiological visits, while home SBP the week before admission was obtained. Clinic SBP was registered just before surgery, during surgery and reanimation. Ambulatory monitoring was also performed (12 h before surgery to 6-8 h after surgery). One month after discharge, clinic SBP was measured at hypertension unit. RESULTS: Eligible participants (N = 50, mean age 74 ±â€Š7 years, 34% men, 26% with history of cardiovascular disease) had higher SBP during the anesthesiologic than the cardiological evaluation (157 ±â€Š23 vs. 144 ±â€Š18 mmHg, P < 0.001), and the former levels were almost identical to those clinically measured just before surgery. A significant white-coat effect between ambulatory and clinic measurements just before surgery (16.4 ±â€Š21 mmHg, P < 0.001) and between entire ambulatory recording and clinic BP measurements the day before surgery (12.4 ±â€Š16 and 24.8 ±â€Š21 mmHg for cardiologic and anesthesiologic visit, respectively, P < 0.001 for both) was noticed, whereas intraoperatively the white-coat effect faded away. There was a greater SBP decline during surgery in patients aged more than 75 years compared with younger, whereas selective treatment discontinuation (except beta blockers and calcium channel blockers) did not modulate SBP trajectories. CONCLUSION: The significant white-coat effect observed in scheduled noncardiac surgery is clinically important and the home BP measurement performed before surgery or ABPM, highly reflects the hypertensive burden of the patient. Blood pressure decrease during surgery is quite pronounced especially in patients aged more than 75 years. Aggressive BP lowering should be avoided.

Arterial stiffness and central hemodynamics in treated hypertensive subjects according to brachial blood pressure classification.

BACKGROUND: International recommendations have classified brachial blood pressure (BP) in subgroups enabling better cardiovascular risk stratification. Central BP is an independent predictor of cardiovascular risk, differing from brachial BP through the predominant influence of arterial stiffness and wave reflections. Central BP has never been studied in relation to international guidelines for brachial BP classification. METHODS: In 580 chronically treated hypertensive subjects we measured: carotid-femoral pulse wave velocity (PWV), carotid artery augmentation index (AI) and carotid blood pressures, using applanation tonometry and pulse wave analysis, and using brachial BP for carotid pressure wave calibration. RESULTS: For each given brachial value, carotid systolic blood pressure (SBP) and PP were significantly lower than the corresponding brachial SBP and PP. This pressure amplification was significantly lower in the 'optimal' and 'normal' BP ranges (6.8-7.4 mmHg) than in the higher BP ranges (10.1-11.3 mmHg), mainly depending on heart rate (HR) and PWV levels. PWV gradually increased as a function of brachial BP classification and was a significant predictor of this classification independently of age, drug treatment, atherosclerotic lesions and even mean BP. Finally, PWV was a highly sensitive marker of the effective BP control throughout all decades of age. CONCLUSION: Under chronic antihypertensive therapy, central BP does not strictly parallel the corresponding brachial BP classification, depending on differences in aortic stiffness and HR. Whether aortic PWV might predict the brachial BP classification and/or the presence of effective BP control, as suggested in this study, needs further confirmation.

The optimal night-time home blood pressure monitoring schedule: agreement with ambulatory blood pressure and association with organ damage.

OBJECTIVE: Night-time home blood pressure (HBP) monitoring has emerged as a feasible, reliable and low-cost alternative to ambulatory blood pressure (ABP) monitoring. This study evaluated the optimal schedule of night-time HBP monitoring in terms of agreement with night-time ABP and association with preclinical target-organ damage. METHODS: Untreated hypertensive adults were evaluated with ABP (24-h) and HBP monitoring (daytime: six days, duplicate morning and evening measurements; night-time: three nights, three-hourly automated measurements/night), and determination of left ventricular mass index, common carotid intima-media thickness and urinary albumin excretion. RESULTS: A total of 94 patients with all nine night-time HBP measurements were analysed [mean age 51.8 ±â€Š11.1 (SD) years, men 57%). By averaging an increasing number of night-time systolic HBP readings, there was a consistent trend towards stronger association of night-time HBP with night-time ABP (correlation coefficients r increased from 0.69 to 0.81), and with target-organ damage indices (for left ventricular mass index r increased from 0.13 to 0.22, carotid intima-media thickness 0.12-0.25, urinary albumin excretion 0.33-0.41). However, no further improvement in the association was observed by averaging more than four to six night-time readings. The diagnostic agreement between HBP and ABP in detecting nondippers was improved by averaging more readings, with a plateau at four readings (single reading: agreement 81%, kappa 0.37; four readings: 88%, 0.49; nine readings: 84%, 0.40). CONCLUSION: A two-night HBP schedule (six readings) appears to be the minimum requirement for a reliable assessment of night-time HBP, which gives reasonable agreement with ABP and association with preclinical organ damage.

Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. METHODS: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ±â€Š0.06 vs. 8.65 ±â€Š0.10, P < 0.001; CAVI: 8.34 ±â€Š0.03 vs. 8.29 ±â€Š0.04, P = 0.40; mean ±â€ŠSEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. CONCLUSION: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

Home blood pressure is as reliable as ambulatory blood pressure in predicting target-organ damage in hypertension.

BACKGROUND: Our objective was to assess the value of home blood pressure (BP) monitoring in comparison to office BP measurements and ambulatory monitoring in predicting hypertension-induced target-organ damage. METHODS: Sixty-eight untreated patients with hypertension with at least two routine prestudy office visits were included (mean age, 48.6 +/- 9.1 [SD] years; 50 men). Office BP was measured in two study visits, home BP was measured for 6 workdays, and ambulatory BP was monitored for 24 h. All BP measurements were obtained using validated electronic devices. Target-organ damage was assessed by measuring the echocardiographic left-ventricular mass index (LVMI), urinary albumin excretion rate (AER) in two overnight urine collections, and carotid-femoral pulse-wave velocity (PWV) (Complior device; Colson, Garges-les-Gonesse, Paris, France). RESULTS: The correlation coefficients of LVMI with office BP were 0.24/0.15 (systolic/diastolic), with home BP 0.35/0.21 (systolic, P < .01), and with 24-h ambulatory BP 0.23/0.19, awake 0.21/0.16, and asleep 0.28/0.26 (asleep, both P < .05). The correlation coefficients of AER with office BP were 0.24/0.31 (diastolic, P < .05), with home BP 0.28/0.26 (both P < .05), and with 24-h ambulatory BP 0.25/0.24, awake 0.24/0.25 (diastolic, P < .05), and asleep 0.26/0.18 (systolic, P < .05). There was a trend for negative correlations between PWV and diastolic BP measurements (not significant). In multiple-regression models assessing independent predictors of each of the three indices of target-organ damage, systolic home BP and age were the only independent predictors of increased LVMI that reached borderline statistical significance. CONCLUSIONS: These data suggest that home BP is as reliable as ambulatory monitoring in predicting hypertension-induced target-organ damage, and is superior to carefully taken office measurements.

Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke.

BACKGROUND: Resistin (RSN) is an adipocytokine involved in insulin resistance, obesity and atherosclerosis. This study aimed to investigate the association between plasma RSN and outcome after ischemic stroke. METHODS: RSN measured within 24 h after the event was related to functional outcome and 5-year survival in 211 subjects with first-ever atherothrombotic ischemic stroke. Prognosis was assessed by the Kaplan Meier and the Cox techniques. RESULTS: The probabilities of death were 80.4%, 46.2% and 15.7% (p<0.001) for patients stratified according to tertiles of RSN (>30 ng/mL, 20-30 ng/mL and<20 ng/mL, respectively). The proportion of dependency (modified Rankin Scale score>or=3) was greater in 5-year survivors with RSN in the upper tertile (6/11 [54.5%]) compared to the middle (20/56 [35.7%]) and the lowest tertile (8/43 [18.6%]; p<0.01). C-reactive protein levels (hazard ratio [HR] 3.96 [95% CI 2.06, 8.91]; p<0.001), coronary heart disease (2.69 [1.62, 6.23]; p<0.001), RSN levels (2.12 [1.31, 5.08] p<0.001), National Institute of Health Stroke Scale score (2.02 [1.23, 4.49]; p<0.01) and age (1.84 [1.19, 3.93]; p<0.01) were independent predictors of death. CONCLUSIONS: High plasma RSN appears to be associated with increased risk of 5-year mortality or disability after atherothrombotic ischemic stroke, independently of other adverse predictors.

Arterial stiffness: determinants and relationship to the metabolic syndrome.

This study aimed to investigate independent determinants of arterial stiffness and evaluate the association of arterial stiffness with the presence of metabolic syndrome (MS). Demographic characteristics, hemodynamic parameters, and cardiovascular (CV) risk factors were assessed in Greek food industry employees with no history of diabetes or CV disease in order to isolate multiple correlates of arterial stiffness as assessed by pulse wave velocity (PWV). Subsequently, logistic regression analysis was performed using as end point the presence of MS, defined according to the National Cholesterol Education Program. Data from 424 participants (mean age 45.3 -/+ 15.5 years, 298 [70.3%] males, average PWV 8.5 -/+ 3.6 m/s) were analyzed. PWV was higher in men (8.8 -/+ 3.1 m/s) compared to women (7.7 -/+ 2.9 m/s, p < 0.01). Age, systolic blood pressure, and heart rate were isolated as multivariate determinants of PWV (adjusted R2 0.511 [p < 0.0001] in men and 0.538 [p < 0.0001] in women). The overall prevalence of the MS was 14.6%, being similar in both genders. Four variables were shown to be independent predictors of the presence of MS: waist circumference >102 cm (men)/88 cm (women) (OR 8.6, [95% CI 2.8, 20.6], p < 0.001), insulin resistance (homeostasis model assessment >4) (6.3, [2.1, 17.6], p < 0.001), total cholesterol >240 mg/dL (5.5, [1.7, 12.4], p < 0.01), PWV >9 m/s (4.1, [1.5, 9.9], p < 0.01). High PWV, which was found to be mostly determined by advanced age, elevated systolic BP, and accelerated heart rate, appeared to exhibit a strong independent association with the presence of MS together with adiposity and insulin resistance. This index should be considered as a useful marker for CV risk stratification.

Effect of barnidipine on blood pressure and serum metabolic parameters in patients with essential hypertension: a pilot study.

The effect of barnidipine, a calcium channel blocker, on metabolic parameters is not well known. The authors conducted the present pilot study to evaluate the possible effects of barnidipine on parameters involved in atherogenesis, oxidative stress, and clotting activity. This open-label intervention study included 40 adult patients with essential hypertension who received barnidipine 10 mg once daily. Barnidipine significantly reduced systolic and diastolic blood pressure as well as isoprostane levels, which represent a reliable marker of oxidative stress. In contrast, barnidipine had a neutral effect on lipid profile and apolipoprotein levels, did not influence glucose homeostasis, had no effect on renal function, and did not cause any changes in electrolyte levels. Moreover, barnidipine did not affect either the clotting/fibrinolytic status (evaluated by measurement of fibrinogen, total plasminogen activator inhibitor, tissue plasminogen activator, and a2 antiplasmin) or the enzymatic activity of the inflammatory/anti-inflammatory mediators lipoprotein-associated phospholipase A2 and paraoxonase 1, respectively. Barnidipine should be mainly considered as an antihypertensive agent with neutral effects on most of the studied metabolic parameters in hypertensive patients. Any antioxidant effect of barnidipine needs further investigation.

Night-time home versus ambulatory blood pressure in determining target organ damage.

OBJECTIVE: This study aimed to evaluate the association of night-time blood pressure (BP) assessed by home blood pressure (HBP) or ambulatory blood pressure (ABP) monitoring with preclinical target organ damage in untreated hypertension. METHODS: Untreated hypertensive study participants were evaluated with ABP monitoring (24-h) and HBP monitoring during daytime (6 days, duplicate morning and evening measurements) and night-time (automated asleep measurements, three nights, 3-hourly measurements/night). Target organ damage was assessed by echocardiographic left ventricular mass index (LVMI), common carotid intima-media thickness (cIMT), urine albumin excretion (UAE), and ankle-brachial index (ABI). RESULTS: A total of 131 study participants were analysed [mean age 52.1 ±â€Š11.9 (SD) years, BMI 29.9 ±â€Š5.3  kg/m2, men 58%, cardiovascular disease history 6.1%]. Daytime and night-time HBP were slightly higher than the respective ABP values (mean difference for systolic daytime/night-time 3.5 ±â€Š10.6/2.6 ±â€Š9.8  mmHg, P < 0.01 for both comparisons and diastolic -0.3 ±â€Š6.8/1.2 ±â€Š6.2  mmHg, P = NS/0.02, respectively). There was a strong correlation between daytime ABP and HBP (r = 0.71/0.72, systolic/diastolic), as well as between the respective night-time values (r = 0.80/0.79; all P < 0.01). Night-time ABP and HBP presented strong and comparable correlations with all the indices of preclinical target organ damage. In multivariate analyses, both LVMI (R2 = 0.26) and cIMT (R2 = 0.25) were determined by night-time systolic HBP, age and male sex; UAE (R2 = 0.28) by night-time systolic HBP and male sex; ABI (R2 = 0.20) by male sex and night-time home pulse pressure. CONCLUSION: In untreated hypertensives, night-time BP assessed by home monitoring appears to be as good as night-time ambulatory monitoring in determining preclinical target organ damage.

Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk who are statin intolerant and have an LDL-C ≥100 and ≥130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Influence of sex on the relation between heart rate and aortic stiffness.

BACKGROUND: Heart rate and aortic pulse wave velocity (PWV) are both cardiovascular risk factors. The aim of this study was to evaluate the influence of sex on the heart rate-PWV relationship in two populations of normotensive and hypertensive men and women. PATIENTS AND METHODS: In a first study, steady-state data describing the heart rate-PWV relationship were determined in 558 normotensive men, 308 normotensive women, 323 hypertensive men and 93 hypertensive women. In a second study, the changes in blood pressure and PWV under atrial pacing at 60, 80 and 100 beats/min were investigated in 15 men and 15 women who were either normotensive or hypertensive. RESULTS: In women in study 1, 26.8% of PWV variance in normotensive patients and 15.4% of PWV variance in hypertensive patients was explained by a multiple regression including only age and systolic blood pressure as covariates. In men in study 1, 27% of PWV variance in normotensive patients and 28.5% of PWV variance in hypertensive patients was explained by a multiple regression including age, systolic blood pressure, weight, and also heart rate, as covariates. In study 2, atrial pacing in the overall population tended to decrease mean blood pressure (P = 0.05) and increase pulse pressure (P = 0.003), with no substantial change in PWV. However, when heart rate increased, PWV tended to decrease in women and to increase in men (interaction: P = 0.07).CONCLUSION Accelerated heart rate influences PWV in both normotensive and hypertensive men and, through this mechanism, could influence cardiovascular risk. However, heart rate does not influence PWV in women.

The effects of the addition of micronised fenofibrate on uric acid metabolism in patients receiving indapamide.

OBJECTIVE: Hyperuricaemia is associated with indapamide administration. In contrast, micronised fenofibrate can significantly decrease serum uric acid levels. However, there are no data on the effect of combination therapy of indapamide with micronised fenofibrate on uric acid metabolism. METHODS: We studied 20 non-diabetic hypertensive patients with mixed dyslipidaemia in whom serum metabolic parameters, including uric acid levels in serum and urine, were measured before and after eight weeks of indapamide administration (2.5 mg once daily). This study was continued for a further eight weeks, when the indapamide was combined with micronised fenofibrate (200 mg once daily). RESULTS: Indapamide significantly decreased mean systolic and diastolic blood pressure (BP) from 153 +/- 9/97 +/- 8 mmHg to 138 +/- 8/93 +/- 4 mmHg (p< 0.05 for both comparisons). A significant increase in serum uric acid levels occurred after indapamide administration (from a mean value of 5.6 +/- 1.3 mg/dl (0.33 +/- 0.07 mmol/l) to 6.4 +/- 1.1 mg/dl (0.38 +/- 0.06 mmol/l), p < 0.01]. This effect was associated with a decrease in the fractional excretion of uric acid (from a mean value of 9.5 +/- 5% to 7 +/- 5.5%, p < 0.05). The addition of micronised fenofibrate significantly decreased plasma fibrinogen levels as well as total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB) and triglycerides, and increased high-density lipoprotein cholesterol and ApoA, levels. Fenofibrate administration was followed by a significant decrease in serum uric acid levels to 4.7 +/- 1.2 mg/dl (0.28 +/- 0.07 mmol/l), p < 0.01, owing to a substantial increase in fractional urate excretion to 11 +/- 3%, p < 0.01. CONCLUSION: The addition of micronised fenofibrate can correct the hyperuricaemic effect of indapamide administration.

Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia.

Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patents. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities.

The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study.

Nebivolol, a selective beta1-lipophilic blocker, achieves blood pressure control by modulating nitric oxide release in addition to b-blockade. This dual mechanism of action could result in minimum interference with lipid metabolism compared to atenolol, a classic beta1-selective blocker. Hypertensive patients commonly exhibit lipid abnormalities and frequently require statins in combination with the anti-hypertensive therapy. We conducted this trial in order to clarify the effect on the metabolic profile of beta-blocker therapy with atenolol or nebivolol alone, or in conjunction with pravastatin. Thirty hypertensive hyperlipidemic men and women (total cholesterol >240 mg/dL [6.2 mmol/L], low-density lipoprotein cholesterol >190 mg/dL [4.9 mmol/L], triglycerides <500 mg/dL [5.6 mmol/L]) were separated in two groups. One group consisted of 15 subjects on atenolol therapy (50 mg daily), and the other group included 15 subjects on nebivolol therapy (5 mg daily). After 12 weeks of beta-blocker therapy, pravastatin (40 mg daily) was added in both groups for another 12 weeks. Atenolol significantly increased triglyceride levels by 19% (P=.05), while nebivolol showed a trend to increase high-density lipoprotein cholesterol by 8% (NS) and to decrease triglyceride levels by 5% (NS). Atenolol significantly increased lipoprotein(a) by 30% (P=.028). Fibrinogen levels were equally and not significantly decreased in both groups by 9% and 7%, respectively. Furthermore, atenolol and nebivolol decreased serum high-sensitivity C-reactive protein levels by 14% (P=.05) and 15% (P=.05), respectively. On the other hand, both atenolol and nebivolol showed a trend to increase homocysteine levels (NS) by 13% and 11%, respectively. Although uric acid levels remained the same, atenolol significantly increased the fractional excretion of uric acid by 33% (P=.03). Following nebivolol administration, glucose levels remained the same, while insulin levels were reduced by 10% and the HOMA index (fasting glucose levels multiplied by fasting insulin levels and divided by 22.5) was reduced by 20% (P=.05). There were no significant differences between the two patient groups in the measured parameters after the administration of beta-blockers, except for triglycerides (P<.05) and the HOMA index (P=.05). The addition of pravastatin to all patients (n=30) decreased total cholesterol by 21% (P<.001), low-density lipoprotein cholesterol by 28% (P<.001), apolipoprotein-B by 22% (P<.001), apolipoprotein-E by 15% (P=.014) and lipoprotein(a) levels by 12% (P=.023). Moreover, homocysteine levels and C-reactive protein were reduced by 17% (P=.05) and 43% (P=.05), respectively. We conclude that nebivolol seems to be a more appropriate therapy in hypertensive patients with hyperlipidemia and carbohydrate intolerance. Finally, the addition of pravastatin could further correct the well-established predictors of cardiovascular events.

Cost estimation of hypertension management based on home blood pressure monitoring alone or combined office and ambulatory blood pressure measurements.

This study aims at estimating the resources consumed and subsequent costs for hypertension management, using home blood pressure (BP) monitoring (HBPM) alone versus combined clinic measurements and ambulatory blood pressure monitoring (C/ABPM). One hundred sixteen untreated hypertensive subjects were randomized to use HBPM or C/ABPM for antihypertensive treatment initiation and titration. Health resources utilized within 12-months follow-up, their respective costs, and hypertension control were assessed. The total cost of the first year of hypertension management was lower in HBPM than C/ABPM arm (€1336.0 vs. €1473.5 per subject, respectively; P < .001). Laboratory tests' cost was identical in both arms. There was no difference in achieved BP control and drug expenditure (HBPM: €233.1 per subject; C/ABPM: €247.6 per subject; P = not significant), whereas the cost of BP measurements and/or visits was higher in C/ABPM arm (€393.9 vs. €516.9, per patient, respectively P < .001). The cost for subsequent years (>1) was €348.9 and €440.2 per subject, respectively for HBPM and C/ABPM arm and €2731.4 versus €3234.3 per subject, respectively (P < .001) for a 5-year projection. HBPM used alone for the first year of hypertension management presents lower cost than C/ABPM, and the same trend is observed in 5-year projection. The results on the resources consumption can be used to make cost estimates for other health-care systems.