Hypertension in patients with Alzheimer's disease--prevalence, characteristics, and impact on clinical outcome. Experience of one neurology center in Poland.

The aim of the study was to evaluate hypertension (HT) prevalence, characteristics, and impact on clinical outcome in patients with Alzheimer's disease (AD). We evaluated 701 patients with AD (249 males, 452 females, and mean age 74.9 ± 7.5 years). As a group representing general population matched with regard to age, education level, and place of residence, we included 762 subjects (438 males, 324 females, and mean age 74.7 ± 4.4 years) from the Polish National Multicenter Health Survey (WOBASZ) studies. The patients with AD were characterized by lower systolic blood pressure (BP) and diastolic BP values (134 ± 21 vs. 151 ± 23 mm Hg, P < .001 and 77 ± 11 vs. 86 ± 12 mm Hg, P < .001, respectively) as well as lower HT prevalence (66% vs. 78.6%, P < .001) compared with the WOBASZ group. In long-term follow-up of AD group, HT and BP levels were not associated with the decline in cognitive functions nor the increased risk of death. Patients with AD were characterized by lower prevalence of HT and other vascular risk factors. BP levels and HT had no impact on clinical outcome.

Prognostic value of novel biomarkers compared with detailed biochemical evaluation in patients with heart failure.

INTRODUCTION: The assessment of prognosis is crucial for the clinical management of patients with heart failure (HF). OBJECTIVES: The aim of the study was to evaluate the usefulness of novel biomarkers for the assessment of prognosis in patients with HF, compared with a detailed assessment based on routine laboratory tests. PATIENTS AND METHODS: The study included 179 patients with HF. In all patients, routine laboratory tests were performed and selected biomarkers were measured (N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, growth hormone, myeloperoxidase, metaloproteinase 9, procollagen type III, soluble toll like receptor 2, insulin growth factor, and neutrophil gelatinase-associated lipocain). The primary endpoint was death or urgent heart transplantation, while the secondary endpoints encompassed primary endpoints plus cardioverter intervention or hospitalization for HF. RESULTS: The mean age of the study group was 52.5 years (91% were men). Most patients had advanced HF. During a 6-month follow-up, 21 primary endpoints and 63 secondary endpoints were recorded. A multiple regression analysis showed that of all laboratory variables and biomarkers, only uric acid and sodium were independent predictors of primary endpoints, and only estimated glomerular filtration rate had a predictive value for secondary endpoints. None of the biomarkers were a significant prognostic factor in the study population. CONCLUSIONS: Biomarkers do not outweigh the value of standard laboratory tests. Routine laboratory workup allows to assess multiorgan damage and provides the most significant prognostic data. Biochemical tests should remain the gold standard for the assessment of prognosis in patients with HF.

Severe chronic heart failure in patients considered for heart transplantation in Poland.

BACKGROUND: Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT). METHODS: Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables. RESULTS: Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT. CONCLUSIONS: Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.

The impact of early menopause on risk of coronary artery disease (PREmature Coronary Artery Disease In Women--PRECADIW case-control study).

BACKGROUND: Despite improved understanding of atherothrombosis pathophysiology, risk factors associated with premature coronary artery disease (CAD) in women are poorly recognized. DESIGN AND METHODS: A single-centre, case-control study comprised 323 women (less than 55 years) with established CAD, enrolled between April 2005 and January 2008, and 347 age-matched healthy women selected from the Multi-Center All-Polish Health Survey. We aimed to assess the relationship of menopause and premature CAD. RESULTS: In multivariate analysis smoking, parental history of premature CVD, diabetes, menopause and hypertension were the strongest risk markers for premature CAD with ORs (95% CI): 3.83 (2.52-5.82); 3.08 (1.85-5.14); 2.89 (1.59-5.23); 2.82 (1.91-4.19); 2.39 (1.16-3.54). The most significant association was found for early postmenopause in a model including the early and late stage of postmenopause (≤ and >3 years of its onset), with OR 4.55 (95% CI 2.82-7.35), higher than other risk factors. The receiver operating characteristic (ROC) curves area revealed a significant increase from 0.81 in that model that included traditional risk factors and parental premature CVD to 0.85 after addition of the early and late stage of postmenopause. CONCLUSIONS: We have shown that smoking and early postmenopausal stage (≤3 years) are the most important determinants of premature CAD followed by parental CVD, diabetes and hypertension.

Is evaluation of complex polymorphism helpful in the assessment of prognosis after percutaneous coronary intervention. A prospective study.

BACKGROUND: Coronary artery disease (CAD) is a complex disorder accounting for the majority of cardiovascular deaths and morbidity. It is believed that genetic factors explain part of the excessive risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI). AIM: To evaluate the influence on long-term prognosis of some genetic polymorphisms affecting renin-angiotensin system, inflammatory response, beta-2 adrenergic receptor, nitric oxide and platelets activity in patients with stable CAD undergoing routine PCI. METHODS: The study population consisted of 110 consecutive male patients with stable angina undergoing elective, single-vessel PCI. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism-based techniques. Follow-up data were obtained by postal questionnaires regarding survival, myocardial infarction and revascularisation procedures. The control group consisted of 78 healthy males. RESULTS: Compared to controls, the distribution of polymorphisms among patients differed with regard to interleukin-1 receptor antagonist and CD14 variants. Patients who had PCI during follow-up in comparison with the remaining patients had a similar genetic profile, but higher triglycerides (1.9 vs 1.5 mmol/L, p = 0.01) and atherogenic index (3.8% vs 3.1%, p = 0.03) and lower percentage of HDL (21.8% vs 25.0%, p = 0.02). Among subjects with any revascularisation procedures, a similar clinical profile was observed. However, they differed from those without any procedures regarding the distribution of angiotensinogen M235T variants (MM%/TM%/TT%) 28%/64%/8% vs 19%/50%/31%, p = 0.048. Stratification for myocardial infarction showed association with selectin E variants (AA%/AC%/CC%) 57.1%/28.6%/14.3% vs 78.8%/21.2%/0%, p = 0.055 and higher triglycerides (2.11 vs 1.57 mmol/L, p = 0.055). CONCLUSIONS: Although we cannot exclude the role of polymorphism in angiotensinogen and selectin E genes, the prognosis of patients post-PCI in our study was mainly influenced by risk factors related to lipid metabolisms.

Characteristics of the heart failure population in Poland: ZOPAN, a multicentre national programme.

BACKGROUND: It is difficult to define the optimal management of elderly heart failure (HF) patients with complex comorbidities. Thus, comprehensive characterisation of HF patients constitutes a crucial pre-condition for the successful management of this fragile population. AIM: To analyse the 'real life' HF patients, including the evaluation of their health conditions, management and their use of public health resources. METHODS AND RESULTS: We examined 822 consecutive patients diagnosed with HF in NYHA classes II-IV in primary care practices. The mean age was 68.5 years, and 56% were male. Only 23% of the patients who were of pre-retirement age remained professionally active. Ischaemic or hypertension aetiology was found in 90% of participants. Nearly all patients had multiple comorbidities. Most patients received converting enzyme inhibitors (88%) and beta-blockers (77%), 60% of them both, although dosing was frequently inadequate. During the six months preceding the study, 31% had cardiovascular hospitalisation and 66% required unscheduled surgery visits. CONCLUSIONS: The real life HF population differs from trial populations. Most of the real life patients who had not yet reached retirement age were professionally inactive, mainly due to a disability caused by cardiovascular conditions. Moreover, extremely few participants were free from any comorbidity. Compared to 20th century Polish data, there has been an improvement in the overall quality of HF-recommended pharmacotherapy. It must be stressed, however, that the percentage of those on optimal dosage remains unsatisfactory.

Inverse association of the obesity predisposing FTO rs9939609 genotype with alcohol consumption and risk for alcohol dependence.

AIMS: To investigate whether the FTO rs9939609 A allele (a risk factor for obesity) is associated with measures of alcohol consumption. DESIGN: Population-based cross-sectional study and two case-control studies. SETTING: Poland and the Warsaw area. PARTICIPANTS: A total of 6584 subjects from the WOBASZ survey and two cohorts of alcohol-dependent patients (n = 145 and n = 148). MEASUREMENTS: Questionnaire data analysis, rs9939609 typing. FINDINGS: Among individuals drinking alcohol, the obesity-associated AA genotype was also associated with lower total ethanol consumption [sex-, age- and body mass index (BMI)-adjusted difference: 0.21 g/day, P = 0.012] and distinct drinking habits with relatively low frequency of drinks but larger volume consumed at a time as evidenced by (i) association between AA and frequency/amount of typical drinks (P = 0.023, multiple logistic regression analysis); (ii) inverse correlation between AA and drink frequency adjusted for drink size (P = 0.007 for distilled spirits, P = 0.018 for beer); (iii) decreased frequency of AA [odds ratio (OR) = 0.46, P = 0.0004] among those who drank small amounts of distilled spirits (≤ 100 ml at a time) but frequently (≥ 1-2 times/week). A decrease of AA was also found in both cohorts of alcohol-dependent patients versus geographically matched subjects from WOBASZ yielding a pooled estimate of OR = 0.59, confidence interval (CI): 0.40-0.88, P = 0.008. Exploratory analysis showed that those with rs9939609 AA reported lower (by 1.22) mean number of cigarettes/day during a year of most intense smoking (P = 0.003) and were older at start of smoking by 0.44 years (P = 0.016). CONCLUSIONS: The FTO AA genotype, independently from its effect on BMI, is associated with measures of ethanol consumption and possibly tobacco smoking.

Prevalence of classical risk factors in Polish women with premature coronary artery disease.

BACKGROUND: It is generally believed that in 50% of perimenopausal women several factors other than classical risk factors play a significant role in the development of premature coronary artery disease (CAD). AIM: To determine the prevalence of five classical risk factors (cigarette smoking, hypertension, diabetes, hyperlipidaemia and obesity) in women aged〈 55 years with premature CAD. METHODS: We performed a single-centre, case-control study in women〈 55 years with angiographically confirmed CAD or troponin-positive acute coronary syndrome. A total of 330 female patients were enrolled between April 2005 and January 2008. The control group consisted of 347 age-matched healthy women from a similar region selected from the National Health Survey WOBASZ study (Polish Multi-centre Population Health Survey) designed to assess the cardiovascular risk in the Polish adult population. RESULTS: Compared to age-matched healthy controls, women with premature CAD had a very high prevalence of traditional risk factors - hypercholesterolaemia (82% vs 68%), smoking (current and former) (81% vs 48%), and hypertension (68% vs 42%). Women with premature CAD had 4.3 times more often diabetes, 1.68 times smoking and 1.63 times hypertension compared to controls. At least one of five classical risk factors was present in 98.8% of patients, compared to 89% in controls, while 10% of patients vs 1.4% of controls had all five of them. CONCLUSIONS: Classical risk factors are present in the vast majority of females with premature CAD - in 99% of them at least one CAD risk factor is present. Premature CAD is most frequently associated with smoking, hypertension and hyperlipidaemia.

Prognosis in patients with severe heart failure referred for heart transplantation--POLKARD-HF 2003-2007.

POLKARD-HF study was a prospective registry of patients, referred for the heart transplantation. The registry collected data on factors influencing the prognosis of patients. The death or the emergency heart transplantation (UNOS status 1) was assumed as the endpoint in the distant observation. 983 patients (88% men, mean age <50) with severe heart failure (HF), referred to 4 centers were analyzed. The average period of observation was 601 days (1 to 1462 days). The Kaplan-Meier probability of surviving 1 year without urgent heart transplantation was 80%, 2 years 70%, and 3 years 67%. HF etiology was dilated cardiomyopathy in 49.4% and ischemic cardiomyopathy in 43.2%. There was only a trend in favor of survival of patients with dilated cardiomyopathy (p=0.1). Prognosis in patients with NYHA classes II and III did not differ but in NYHA IV, was significantly worse. The probability of 6-month survival was 60%, 1-year--50%, and 3-year--40%. In Kaplan-Meier analysis survival was worse for pts with pulmonary artery systolic pressure ≥50 mmHg, pulmonary capillary pressure ≥25 mmHg, left ventricular ejection fraction ≤17%, functional NYHA class IV, systemic systolic arterial pressure ≤90 mmHg, hsCRP≥6.5 mg/L, NTpro-BNP≥4302, Na serum level≤135 mEq/L, BMI≤23.8, and HFSS≤7.19. When only biochemistry parameters were analyzed using ROC, sodium plasma levels ≤135 mEq/L alone gave ROC 58.3% and inclusion of NTpro-BNP≥4302 pg/mL into the model, increased the predictive value up to 61.2%.

Acute coronary syndrome--how to reduce the time from the onset of chest pain to treatment?

BACKGROUND: Enormous progress in treating acute coronary syndrome (ACS) and shortening the time between the onset of pain and intervention has been made in recent years. However, the time from the beginning of pain to the call for help is still too long. AIM: To establish the causes of delayed call for help by ACS patients and to answer the question how to shorten that time. An additional aim was to examine the knowledge about myocardial infarction (MI) among patients with ACS. METHODS: The study group consisted of 349 patients treated for ACS at the CCU. Nurses interviewed the patients using a questionnaire focused on demographic data, ACS characteristics, risk factors and situations which occurred between pain onset and arrival at the CCU. The data were analysed in relation to sex, place of living, education level, professional activity, history of MI, diabetes, and hypertension. RESULTS: The time between the onset of symptoms and the call for medical help ranged from 4 to 1140 min. The longest delay was reported by patients aged 56-70 years. Half of them called for help later than after 3 hours. Women waited longer than men. They also waited longer for an ambulance - 20 vs. 15 min (p <0.01). Professionally active patients called for help sooner: 82.7 vs. 120.2 min (p=0.02). Warsaw inhabitants waited longer than those living in other towns and in rural areas (p=0.04). The main causes of delay were: being confident that symptoms would subside (201 patients - 57.6%), or that the symptoms were not associated with heart disease (45 patients - 12.9%). The 41.5% of patients knew what MI was, 37.2% were familiar with features of ischaemic chest pain. Symptoms of pain were known to 44.4% of patients with ACS history vs. 32.2% of previously untreated (p=0.02), blood pressure levels were known to 51.4 vs. 45.4% (NS), and cholesterol to 29.9 vs. 20.0% (p=0.03). A general practitioner was mentioned as the source of information by 44.4% of patients and a nurse - by 11.5%. CONCLUSIONS: The main cause of delayed call for help in ACS patients was a poor level of knowledge about MI, risk factors and management at the time of chest pain onset. Education concerning these issues should be started at school. Physicians, nurses and media should participate in the education.

Significance of dyslipidaemia in patients with heart failure of unexplained aetiology.

BACKGROUND: Dyslipidaemia has been studied in the prognosis of heart failure (HF). Little is known about the role of dyslipidaemia in the aetiopathogenesis of dilated cardiomyopathy (DCM). AIM: To assess (1) serum lipid levels in DCM considering the severity of heart failure; (2) the association between DCM and lipid abnormalities; (3) prognostic significance of lipids in DCM. METHODS: The study group consisted of 100 patients with angiographically proven DCM [mean age 42 years, 80% males, 65% in NYHA class III-IV, mean left ventricular ejection fraction (LVEF) 32%], whose fasting serum lipids had been assessed during diagnosis between 1992 and 2001. Patients' lipid levels were compared with those observed in healthy controls (n=100), age-, gender-, and BMI-matched and related to findings reported in population samples from WHO Pol-MONICA studies from: 1993 (n=526), 1997/1998 (n=526) and 2001 (n=1364). Three (3%) patients received lipid-lowering drugs. Transplant-free survival was assessed in the study group. In the statistical analysis, nonparametric Wilcoxon test and uni- and multivariate logistic and Cox regression analyses were used. RESULTS: Serum total cholesterol (TC), LDL (LDL-C) and HDL cholesterol (HDL-C) tended to be lower (differences NS) in NYHA class III-IV patients vs. class I-II (TC: 196.9+/-45.5 vs. 207.9+/-47.1 mg/dl, LDL-C 126.2+/-37.5 vs. 128.5+/-42.7 mg/dl, HDL-C 44.2+/-11.3 vs. 44.7+/- +/-13.7 mg/dl, respectively), and triglycerides (TG) were lower in advanced HF vs. NYHA class I-II (135.9+/-51 vs. 170.3+/-63.4 mg/dl, p=0.004). In DCM patients HDL-C was lower than in controls (44.1+/-12.1 vs. 54.3+/-17.6 mg/dl, p <0.001), and TG level was higher (147.9+/-58.1 vs. 114.1+/-61.6 mg/dl, p <0.001). HDL-C and TG levels in controls were similar to those observed in population samples. Multivariate analysis with age, low HDL (defined as <40 mg/dl for males, and <50 mg/dl for females), and hyperTG (TG l150 mg/dl) showed that both low HDL-C (OR=2.31; 95% CI 1.2-4.457, p=0.0122), and hyperTG (OR=1.978, 95% CI 1.029-3.799, p=0.0407) were independently associated with DCM. Low HDL-C level occurred more frequently in female DCM patients vs. in males (65 vs. 33.8%, p=0.022). There was a trend towards more frequent occurrence of hyperTG in male patients vs. females (42.5 vs. 20%, p=0.11). The mean follow-up time was 7.32+/-4.7 years. In Cox univariate analysis low TC tended to be a prognostic factor (p=0.067), but in Cox multivariate analysis only NYHA class (HR=1.7, 95% CI 1.136-2.541; p=0.01) and LVEF (HR=0.963, 95% CI 0.932-0.996; p=0.027) turned out to be independent predictors of poor outcome. CONCLUSION: Dyslipidaemia might play a role in the aetiopathogenesis of DCM. Low TC is not an independent prognostic factor in DCM.

Effect of protein convertase subtilisin/kexin type 9 (PCSK9) 46L gene polymorphism on LDL cholesterol concentration in a Polish adult population.

The purpose was to study the effect of PCSK9 46L on cholesterol concentration and cardiovascular morbidity. By comparing 176 carriers with 6618 non-carriers identified through a cross-sectional population study (WOBASZ) we confirmed the LDL lowering effect of PCSK9 46L and demonstrated that it increases with the concentration of LDL. We noted that PCSK9 46L was associated with tendency for protection from myocardial infarction but not stroke suggesting a difference in the effect on susceptibility to these disorders.