Reduced kidney function estimated by cystatin C and clinical outcomes in hypertensive patients with coronary artery disease: association with homocysteine and other cardiovascular risk factors.

AIMS: To evaluate the association between serum cystatin C and homocysteine concentrations, cardiovascular risk factors and cardiovascular events in hypertensive patients with coronary artery disease (CAD). METHODS: 260 patients with hypertension and CAD (mean age 56.9 +/- 9.3) were included. During a mean 40-month follow-up the combined end-point of death from all causes, non-fatal myocardial infarction and stroke or coronary revascularization was assessed. RESULTS: Subjects in the highest serum cystatin C quartile (>103.4 nmol/l) as compared with the lowest were older, were characterized by a higher frequency of multivessel CAD, higher levels of homocysteine (13.2 +/- 5.2 vs. 11.4 +/- 4.2 micromol/l; p < 0.01), fibrinogen and high-sensitivity C-reactive protein and by an increased intima-media thickness. Combined end-point occurred twice as frequently in the 4th quartile of serum cystatin C as compared with the 1st quartile (10.8 vs. 20.3%; p = 0.11). In an univariate analysis, but not in a multivariate model, cystatin C concentration predicted the combined end-point (Exp(B) = 1.096; p < 0.05). CONCLUSION: In hypertensive patients with CAD, serum cystatin C level was independently associated with the extent of CAD, homocysteine plasma level and traditional vascular risk factors. However, serum cystatin C concentration did not independently predict the combined end-point.

Genetic variants in hypertensive patients with coronary artery disease and coexisting atheromatous renal artery stenosis.

BACKGROUND: Atheromatous renal artery stenosis (ARAS) often coexists with coronary artery disease (CAD). This study evaluated the prevalence of three polymorphisms: angiotensin-converting enzyme (ACE) insertion/deletion (Ins/Del), endothelial nitric oxide synthase (eNOS) Glu298Asp, and methylenetetrahydrofolate reductase (MTHFR) C677T, in hypertensive patients referred for coronary and renal angiography. MATERIAL/METHODS: The study included 223 hypertensive patients divided into three groups: 72 patients without significant CAD or evidence of ARAS, 111 patients with significant CAD but no ARAS, and 40 patients with coexisting significant CAD and evidence of ARAS. The control group consisted of 195 age- and sex-matched healthy subjects. RESULTS: Patients with coexisting significant CAD and evidence of ARAS were older (p=0.03), less frequently obese (p=0.02), and more likely to have peripheral carotid or femoral artery disease (PAD) (p=0.02) compared with patients with significant CAD but no ARAS. They differed in terms of ACE Del/Del genotype distribution (40% vs. 17.1%, respectively, p=0.007). In a multivariate analysis the independent predictors of ARAS were PAD (OR: 3.7, 95%CI: 1.1-12.3, p=0.005) and ACE Del/Del polymorphism (OR: 3.3, 95%CI: 1.3-8.2, p=0.01). There was a higher prevalence of eNOS Asp/Asp genotype in all patients with significant CAD than in controls (9.3% vs. 3.6%, respectively, p=0.02), but no difference in MTHFR polymorphism between the studied groups was found. CONCLUSIONS: In the hypertensive population referred for coronary and renal angiography, the ACE insertion/deletion variant but not eNOS Glu298Asp or MTHFR C677T polymorphism, seems to coexist with atheromatous renal artery stenosis.

Cardiovascular risk factors in hypertensive patients with coronary artery disease and coexisting renal artery stenosis.

OBJECTIVE: The aim of our study was to examine the association between the presence of atherosclerotic renal artery stenosis (RAS) and coexisting cardiovascular risk factors in hypertensive patients with coronary artery disease (CAD). METHODS: A total of 333 consecutive hypertensive patients (239 men, 94 women) with CAD underwent clinically indicated non-emergency coronary angiography, followed by renal angiography. Before catheterization clinical examination was performed to determine demographics, cardiac history, known duration of hypertension, cardiovascular risk factors, features of extracoronary vascular disease and related comorbidities. Blood samples for all biochemical evaluations--including highly sensitive C-reactive protein (hsCRP), fibrinogen and homocysteine--were taken. Ambulatory blood pressure monitoring (ABPM), echocardiography and carotid and femoral ultrasound followed by a duplex colour Doppler examination were performed. RESULTS: Significant RAS (> 50% lumen narrowing) was identified in 40 patients (12%) and non-significant RAS (< 50%) was found in 45 (13.5%) subjects. Patients with significant RAS were older (59.8 versus 56.6 years, P < 0.05) and were characterized by higher systolic ambulatory blood pressure level. Patients with RAS had significantly higher levels of creatinine, hsCRP, fibrinogen and homocysteine and lower creatinine clearance than patients without RAS. Multivessel coronary artery disease (MVD) was more frequent in patients with significant RAS. Patients with significant RAS had significantly higher left ventricular mass index (LVMI) and lower ejection fraction (EF) as compared with those without RAS. Patients with RAS were more often characterized by the presence of carotid and femoral artery atherosclerosis and significantly more pronounced increase in carotid intima-media thickness (IMT) as compared with non-RAS subjects. In a multivariate stepwise logistic regression model carotid IMT [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.03-1.29, P < 0.05], number of coronary arteries stenosed (OR 1.61; 95% CI 1.01-2.56, P < 0.05), creatinine concentration (for 10 micromol/l increase, OR 1.15; 95% CI 1.04-1.28, P < 0.01), body mass index (BMI) (OR 0.86; 95% CI 0.75-0.97, P < 0.05) and number of antihypertensive drugs (OR 1.76; 95% CI 1.18-2.62, P < 0.05) were independently associated with RAS. The areas under receiver operating characteristic curves for carotid IMT, number of coronary arteries stenosed, creatinine concentration, BMI and number of antihypertensive drugs were 0.749, 0.633, 0.703, 0.350 and 0.677, respectively (P < 0.01 for all values). CONCLUSIONS: In conclusion, renal artery stenosis is prevalent in a significant proportion of patients undergoing cardiac catheterization. Renal angiography should be considered particularly in hypertensive patients with multivessel coronary disease coexisting with cardiovascular risk factors, even moderately impaired renal function and increased carotid IMT or vascular disease elsewhere.

Carotid intima-media thickness as a marker of cardiovascular risk in hypertensive patients with coronary artery disease.

BACKGROUND: The aim of this study was to examine the significance of ultrasound-measured carotid intima-media thickness (CIMT) in high-risk patients with hypertension and coronary artery disease (CAD), as an independent prognostic factor in determining the risk of all-cause death or future cardiovascular events. METHODS: The study included 297 consecutive patients (mean age +/- SD, 57 +/- 9.4 years) with diagnosed hypertension and CAD, referred for coronary angiography. The mean of maximal CIMT in two arterial segments bilaterally was calculated. The primary endpoint was a patient's death from all causes. Death, stroke, or myocardial infarction comprised the secondary, composite endpoint. RESULTS: There was a follow-up of 1 to 79 (mean, 41) months. The predictors of death in a multivariate Cox proportional hazards model were the number of stenosed coronary arteries (P = .007) and CIMT (P = .001). The risk of the secondary, composite endpoint (death, stroke, or myocardial infarction) was determined by diabetes (P = .008) and CIMT (P = .010). Nearly 99% of patients with "low CIMT" (< or =1.13 mm) survived for 5 years, versus 78% with "high CIMT" >1.13 mm (log-rank test; P < .001). For the secondary, composite endpoint (death, stroke, or myocardial infarction), the event-free survival rate was 95% (low CIMT), versus 74% after 5 years (high CIMT) (P < .008). CONCLUSIONS: Intima-media thickness of the carotid arteries is a strong and independent predictor of death and serious cardiovascular events in hypertensive patients with CAD referred for coronary angiography.

Decreased plasma concentration of a novel anti-inflammatory protein--adiponectin--in hypertensive men with coronary artery disease.

AIMS: Recent studies indicate that adiponectin may have anti-inflammatory and anti-atherogenic properties, suggesting that hypoadiponectinemia can play a role in the pathogenesis of cardiovascular disease. Therefore the aim of the study was to assess plasma adiponectin concentration in hypertensive male patients with coronary artery disease (CAD). Associations of adiponectinemia with other cardiovascular risk factors were also analysed. METHODS AND RESULTS: The study included 99 consecutive male patients (median age 57 years) with hypertension and CAD who at the same time underwent coronary and renal angiography. The control group consisted of 62 BMI-matched healthy male blood donors (median age 48 years). Plasma adiponectin level was significantly lower in the CAD group as compared to the control group (4.01 +/- 0.18 vs. 4.88 +/- 0.24 microg/ml; p<0.01). There were no differences in plasma adiponectin concentration between hypertensive CAD patients with and without atherosclerotic renal artery stenosis. In the CAD group plasma adiponectin concentration correlated with levels of creatinine (r=0.56; p<0.001), HDL cholesterol (r=0.24; p<0.05), BMI (r=-0.33; p<0.001), glucose (r=-0.22; p<0.05) and triglycerides (r=-0.25; p<0.05). No correlation was found between plasma adiponectin and homocysteine concentrations. In a multivariate stepwise logistic regression model increasing concentrations of adiponectin were independently and significantly associated with a lower risk of CAD (OR 0.58 95% CI 0.42-0.81 p<0.001). CONCLUSIONS: Our results showed decreased plasma adiponectin concentration in the studied group of hypertensive men with CAD as compared to normotensive healthy subjects. This may suggest that decreased plasma adiponectin concentration is associated with a higher risk of CAD.

The role of biochemical tests and clinical symptoms in differential diagnosis of primary aldosteronism.

BACKGROUND: Primary aldosteronism (PA) is a secondary form of hypertension resulting from the autonomous hypersecretion of aldosterone. The recognition of PA has an important impact on clinical management, since the choice of therapy is different - surgical for adenoma and medical for hyperplasia. AIM: To evaluate patients with PA in regard to clinical and biochemical factors differentiating between adenoma of adrenal cortex (APA) and idiopathic adrenal hyperplasia (IHA). METHODS: We retrospectively analysed 62 patients with PA (33 females, 29 males, mean age 49.3+/-12.5 years, range 26-78) diagnosed in the Department of Hypertension between 1990-2001. In 37 patients (mean age 47.4+/-12.1 years, 22 females, 15 males) APA was diagnosed whereas in the remaining 26 patients (mean age 52.2+/-12.6 years, 14 males, 11 females) IHA was detected. Clinical manifestation, biochemical, serum aldosterone (SA), plasma renin activity (PRA) as well as echocardiographic parameters and blood pressure (BP) levels were evaluated. Diagnostic accuracy of computed tomography (CT) and scintigraphy was also assessed. RESULTS: Mean systolic BP was significantly higher in the patients with APA. Both groups had similar mean diastolic BP. Severe hypertension, resistant to three or more medications, was found in 63.3% of all patients. Muscle weakness was reported by 39.7% of patients, polyuria - by 19%, and polydypsia - by 10.3% of patients. Patients with muscle weakness had higher mean systolic BP level and lower plasma potassium level than patients without this complaint. Symptoms suggesting cardiac arrhythmia were reported by 45% of patients. A normal potassium level was found in 25.8% of all patients. The hypokalemic patients were younger, had shorter known duration of hypertension, higher mean systolic BP level and higher SA concentration than the normokalemic patients. Supine SA levels were significantly higher in the APA group than in the IHA group (50.3+/-29.0 ng% vs 30.5+/-14.7 ng%; p<0.001). The SA/PRA ratio higher than 30:1 was found in all patients. Response to postural test with a rise in SA concentration higher than 30% was observed in 40% patients with APA and in 87.5% patients with IHA (p<0.0001). There was a strong correlation between supine and upright SA level, and systolic and diastolic BP level as well as plasma potassium level. Left ventricular hypertrophy was present in 60% of patients. The differentiation between APA and IHA was possible using CT, scintigraphy or both methods in 75%, 89.2% and 100% of patients, respectively. CONCLUSIONS: One quarter of patients with PA were normokalemic. PA should be suspected especially in patients with severe hypertension, resistant to three or more antihypertensive drugs. Changes in SA concentration during the postural tests such as CT and scintigraphy are useful for differentiation between APA and IHA.

Relationship between obstructive sleep apnea and markers of cardiovascular alterations in never-treated hypertensive patients.

We addressed a question if there is a relationship between severity of newly diagnosed obstructive sleep apnea (OSA) and markers of cardiovascular alterations in middle-aged untreated hypertensive patients. In 121 consecutive patients with never-treated essential hypertension (mean age 35.9±10.1 years; 97 men and 24 women) evaluation of office and ambulatory blood pressure (BP) measurements, metabolic syndrome (MS) components and markers of alterations in cardiovascular system including left ventricular structure and function, carotid artery wall intima-media thickness (cIMT) and urinary albumin excretion (UAE) was performed. OSA was classified as mild (apnea/hypopnea index (AHI) 5-15 events h(-1)) or moderate-to-severe (AHI >15 events h(-1)). Mild and moderate-to-severe OSA were diagnosed in 30% and 20% of patients, respectively. No differences in nighttime BP levels and decline between patients with and without OSA were observed. The patients with moderate-to-severe OSA were characterized by higher cIMT (0.74±0.16 vs. 0.60±0.15 mm; P=0.001), UAE (14.5±6.9 vs. 10.0±8.0 mg 24 h(-1); P=0.014), relative wall thickness (0.42±0.05 vs. 0.39±0.05; P=0.023) and by a higher degree of diastolic dysfunction (E'-wave velocity 11.4±3.2 vs. 15.5±3.8 m s(-1); P<0.001) as compared with the patients without OSA. In multivariate analysis, AHI independently of BP and MS components correlated with UAE, relative wall thickness and E'-wave velocity. In the middle-aged never-treated hypertensive patients, moderate-to-severe OSA correlates with markers of cardiovascular alterations independently of BP levels and MS components.

[Mid-aortic syndrome in 18 year-old woman with arterial hypertension and bilateral renal artery stenosis]. / Zespól aorty brzusznej u 18-letniej chorej z nadcisnieniem tetniczym i obustronnym zwezeniem tetnic nerkowych.

Mid-aortic syndrome (MAS) is characterised by narrowing of the abdominal aorta, often with involvement of the renal and splanchnic arterial branches. Although uncommon, MAS is an important cause of renovascular hypertension in children and adolescents and should be considered in the differential diagnosis of hypertension . Hypertension is typically severe and often difficult to manage. The management of MAS should always be individualised and may include percutaneous transluminal renal angioplasty, stent implantation or surgical revascularisation. We present a 18 year-old woman with hypertension and MAS coexisting with bilateral renal artery stenosis who underwent left renal artery angioplasty and than was followed-up for one year.

Adrenomedullin concentrations at two time points following myocardial infarction and prediction of mid-term outcomes.

INTRODUCTION: Adrenomedullin (ADM) is a vasopeptide with multiple actions in the cardiovascular system and a potentially powerful tool in comparison to some of the well-established unimodal biomarkers of risk stratification in myocardial infarction (MI). Previous studies on ADM in acute MI were based on single assessment. Therefore the aim of the study was to examine the relation between ADM plasma concentrations assessed at different time points following MI and outcomes. MATERIAL AND METHODS: The study included 127 patients with acute MI treated with percutaneous coronary intervention and 60 healthy individuals as controls. Adrenomedullin concentration was assessed at baseline in all study subjects and 48 h after admission in patients with MI. The primary endpoint consisted of all-cause death, nonfatal myocardial infarction, stroke and the need of target vessel revascularization at 6-month follow-up. RESULTS: Mean ADM plasma concentration on admission was higher in patients with MI than in controls (30.3 ±14.3 pmol/l vs. 14.6 ±4.7 pmol/l, p < 0.0001). There was no significant difference between ADM concentration after 48 h (30.6 ±12.3 pmol/l) and on admission. The primary endpoint occurred in 9.4% of patients with MI. Multivariable analysis showed that ADM concentration at 48 h after admission (OR = 2.121, 95% CI 1.180-3.810 for every increase of 10 pmol/l, p = 0.012) was the only independent predictor of the primary endpoint. CONCLUSIONS: In patients with acute MI adrenomedullin plasma concentration assessed at 48 h after admission, but not ADM concentration at baseline, is an independent predictor of major adverse cardiovascular events at mid-term follow-up.

The 24-h blood pressure measurement may predict mortality and cardiovascular events in hypertensive patients with coronary artery disease.

The aim of this prospective study was to evaluate the relationship between 24-h blood pressure (BP) values and cardiovascular events in hypertensive patients with coronary artery disease in the long-term observation. Two hundred and seventy-four patients (mean age 56.9+/-9.3 years, 197 male, 77 female) who underwent coronary and renal angiography were investigated. Baseline characteristics included clinical and biochemical evaluations, 24-h BP measurement and standardized auscultatory readings - clinic BP. The composite end-point of death from all causes, nonfatal acute myocardial infarction, coronary revascularization and stroke were assessed at mean 40 months follow-up. Patients with the composite end-point had higher mean 24-h systolic BP (SBP) and diastolic BP (DBP) levels (124/74 vs. 117/71 mmHg; P<0.001 and P<0.05 for SBP and DBP, respectively), higher mean daytime SBP and DBP (127/76 vs. 119/72 mmHg; P<0.001 and P<0.05 for SBP and DBP, respectively) and higher night-time SBP and DBP (121/69 vs. 111/65 mmHg; P<0.001 and P<0.05 for SBP and DBP, respectively) at baseline. There were no differences in systolic and diastolic clinic BP levels between patients with and without the combined end-point. Multivariate Cox model revealed that only a number of coronary arteries stenosed and 24-h systolic BP level were independent predictors of occurrence of the composite end-point. In conclusion, our results indicate that 24-h BP measurement made in hospital but not the clinic standardized auscultatory readings predicts cardiovascular risk.

Characterization of insomnia in patients with essential hypertension.

INTRODUCTION: Insomnia may increase risk of cardiovascular events. There is little data available reporting the prevalence and clinical relevance of insomnia in patients with essential hypertension. Therefore, the aim of the study was to investigate the relationship between insomnia and different clinical and biochemical parameters in essential hypertension patients. METHODS: Four hundred and thirty-two patients (mean age 47+/-13 years; 253 male, 179 female) with essential hypertension were screened for insomnia using the athens Insomnia Scale (AIS). Several variables including age, sex, known duration of hypertension, body mass index, creatinine, left ventricular mass index, coexisting disorders, smoking status and alcohol use were analysed. Twenty-four-hour ambulatory blood pressure measurements (ABPM) were performed. RESULTS: Among patients included in the study, 207 subjects (mean age: 49+/-13 years; 47.9%) had an AIS score of 15 or higher and were identified as insomniacs. Insomnia was more frequent in women than in men (60.9% vs 38.7%, p<0.001) and was reported more frequently in patients with coronary artery disease. Subjects with insomnia were older and had longer duration of hypertension. There were no differences between insomniacs and non-insomniacs in ABPM parameters. A relationship was found between the number of antihypertensive drugs and insomnia frequency. There were correlation between AIS score and age (r=0.21; p<0.001) and duration of hypertension (r=0.22; p<0.001). In the sub-group of untreated essential hypertension patients, there were negative correlations between AIS score and night fall in systolic and diastolic blood pressure. CONCLUSION: Our results showed that insomnia is common in patients with essential hypertension and indicate an association between insomnia and gender, known duration of hypertension and number of hypertensive drugs taken. Untreated essential hypertension insomniacs were characterized by less pronounced nocturnal fall in both systolic and diastolic blood pressure compared with non-insomniacs.