Jerzy Gąsowski

Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension.

This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP) measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP reduction. Although many methodological problems still hinder the wide clinical application of parameters of arterial stiffness, these will likely contribute to cardiovascular assessment and management in future clinical practice. Each of the abovementioned parameters reflects a different characteristic of the atherosclerotic process, involving functional and/or morphological changes in the vessel wall. Therefore, acquiring simultaneous measurements of different parameters of vascular function and structure could theoretically enhance the power to improve risk stratification. Continuous technological effort is necessary to refine our methods of investigation in order to detect early arterial abnormalities. Arterial stiffness and its consequences represent the great challenge of the twenty-first century for affluent countries, and “de-stiffening” will be the goal of the next decades.

Severe frailty and cognitive impairment are related to higher mortality in 12-month follow-up of nursing home residents.

Frailty syndrome (FS) and cognitive impairment are associated with an increased risk of falls, disability, hospitalization and death. We investigated prognostic meaning of FS and cognitive impairment in persons ≥ 65 years, living in 2 nursing homes. Information about the health status of patients was gathered from history, medical documentation, test assessing FS, according to the Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) and the Mini-Mental State Examination (MMSE). The study group included 66 women and 20 men, between 66 and 101 years of age (mean ± S.D.=83.8 ± 8.3 years). The frequency of severe frailty (CSHA-CFS=7) among the elderly living in nursing homes was 34.9%, while severe cognitive impairment (MMSE<18) was present in 55.8%. Residents with severe FS and MMSE<18 consisted 33.7% of examined and 50.0% of those who died during 12-month follow-up, p<0.05. Individuals with severe FS and severe cognitive impairment (n=29) as compared to all other patients, were significantly less probable (59% vs. 79%, p=0.03) to survive one year. Neither frailty, nor dementia, nor severe FS or cognitive impairment when considered separately was associated with higher mortality rate. The risk assessment in severely disabled geriatric patients is best performed with measures of functional and cognitive function considered jointly, but not separately.

The prevalence of falls and their relation to visual and hearing impairments among a nation-wide cohort of older Poles

Falls are a geriatric syndrome which affects the physical and psychological well-being of the aged. So far, in Poland there have not been any population-based data on the prevalence of falls among the elderly. The aim of this analysis was to assess the prevalence of falls, their circumstances and consequences in the Polish population aged 65 years and older in comparison to younger respondents aged 55-59 years, and the relation of falls to visual and hearing deficits. Mean age of the 4920 elderly subjects (51.6% men) was 79.4±8.7 years. Falls in the past year were reported by 10.4% of the younger and 19.1% of the older subjects. In both groups falls occurred more frequently in women (11.9% vs. 8.7%, p=0.03 in the younger and 22.7% vs. 13.2%, p<0.001 in the older group). In the group of older subjects falls occurred most often during walking (66.7% vs. 50.7% in the group of 55-59 years old), p=0.005), while the younger more often fell while practicing sports (5.48% vs. 0.8% in the group 65+, p<0.001) and risky activities (respectively: 13.7% vs. 4.9%, p=0.002). A similar percentage of younger and older fallers reported one (44.0% and 46.1% respectively) or more falls (56.1% and 53.9%; p=0.6). The percentage of recurrent fallers grew with increasing age (Cc=0.177; p<0.001). The prevalence of injurious falls was similar in the younger and older groups (45.4% and 42.8%, p=0.53). In both genders fall-related injuries were more frequent in younger elderly (65-74 years old) and in subjects 90 years old and older. In the non-standardized analysis and after adjustment for age and gender visual and hearing impairments and its degree were associated with falls but both relations lost statistical significance after adjustment for a set of explanatory variables. Despite somewhat lower estimates, falls in older Poles are no less an important factor influencing overall health than in other populations. The higher prevalence of multiple falls should draw attention of the health-care policy makers. Sensory impairment may add to the risk of falls and should be adequately taken care of, however the priority in the future fall prevention initiative should be given to stronger factors, such as age, type of activity, overall health, cognitive function and functional status.

High disease activity in ankylosing spondylitis is associated with increased serum sclerostin level and decreased wingless protein-3a signaling but is not linked with greater structural damage

BackgroundClinical activity of ankylosing spondylitis (AS) predicts the natural course of the disease and the response to treatment. Several molecules are involved in new bone formation resulting in structural damage in patients with AS. However, the link between the clinical and molecular phenomena has not yet been fully established. The aim of the study was to investigate the relation between markers of bone remodeling and inflammation with clinical activity and structural damage in AS.MethodsWe assessed the serum levels of sclerostin, Dickkopf-1 protein, Wingless protein-3a, bone morphogenic protein-7, matrix metalloproteinase-3, osteoprotegerin, bone alkaline phosphatase and inflammatory markers in 50 AS patients with high disease activity (BASDAI ≥ 4), 28 with low disease activity (BASDAI <4), and 23 healthy controls. Cervical and lumbar spine x-rays were performed in 46 patients to measure structural damage (mSASSS).ResultsSclerostin level was significantly greater in high disease activity patients than in controls. Wingless protein-3a and Dikkopf-1 protein levels were significantly lower in high activity group compared to low activity group and controls. Negative correlation was found between sclerostin and Dikkopf-1 protein in high activity group (R = −0.28, P = 0.048). The median mSASSS values were not different between patient groups.ConclusionsHigher disease activity in AS may not be per se associated with greater new bone formation.

Effect of tumour necrosis factor-α inhibitor on serum level of dickkopf-1 protein and bone morphogenetic protein-7 in ankylosing spondylitis patients with high disease activity

Objectives: To examine changes in serum levels of the bone remodelling molecules dickkopf-1 (Dkk-1), sclerostin, wingless-type protein-3a (Wnt-3a), and bone morphogenetic protein-7 (BMP-7) during 6 months of anti-tumour necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients with high disease activity. Method: We included 40 patients with axial AS: 20 patients with high disease activity were assigned to treatment with TNF inhibitor and 20 with low disease activity were assigned to non-steroidal anti-inflammatory drug (NSAID) treatment. Markers of bone remodelling and inflammation were assessed at baseline and after 6 months. Results: In the TNF inhibitor-treated group Dkk-1 decreased significantly from 196.8 pg/mL [95% confidence interval (CI) 94.1–399.0] to 116.3 pg/mL (95% CI 38.0–301.6) and BMP-7 increased significantly from 1.4 pg/mL (95% CI 0–23.0) to 20.3 pg/mL (95% CI 4.9–41.3). There was a significant negative correlation between Dkk-1 and BMP-7 at 6 months (r = –0.64, p = 0.004) in this group. Non-parametric regression analysis adjusted for disease duration, age, sex, baseline modified Stoke’s Ankylosing Spondylitis Spine Score (mSASSS), and baseline C-reactive protein (CRP) confirmed a statistically significant effect of treatment on time-related changes of Dkk-1 and BMP-7. Erythrocyte sedimentation rate (ESR), CRP, and also the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score decreased significantly in the anti-TNF-treated group. Conclusions: Among the potential biomarkers of bone remodelling in AS, Dkk-1 and BMP-7 displayed significant time alterations and correlative interactions during anti-TNF treatment.

Disparate effects of anti-TNF-α therapies on measures of disease activity and mediators of endothelial damage in ankylosing spondylitis.

BACKGROUND Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethylarginine (SDMA) levels in AS, RA, and healthy controls, and in the anti-TNF treated patients with active AS. METHODS In 78AS patients and 29 RA patients who were anti-TNF treatment naive at baseline, along with 23 healthy control subjects, we assessed erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), ADMA, and SDMA. For AS patients, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain VAS and patients global activity of disease were calculated. After 6 months, we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated. RESULTS The baseline mean (SD) plasma ADMA concentration of AS patients was 0.64 (0.19) μmol/l and did not differ from controls (0.65 [0.19] μmol/l, p > 0.05). In the RA group, ADMA concentration was higher than in controls (0.77 vs. 0.65 μmol/l, p < 0.05). Both at baseline and at follow-up, ADMA levels correlated positively with BASDAI (R = 0.52, p = 0.02, and R = 0.47, p = 0.04, baseline and follow-up, respectively). Six months of anti-TNF treatment did not influence ADMA concentration (0.51 [0.12] vs. 0.51 [0.11] μmol/l, p = 0.70). CONCLUSION An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity (BASDAI) and inflammation (ESR, CRP) may suggest either a lack of effect, or, even if such an effect were to take place, it needs not imply measurable changes in blood ADMA.

Antioxidants modify the relationship between endothelin-1 level and glucose metabolism–associated parameters

Glucose handling impairment and oxidative stress are implicated in the overexpression of endothelin-1 (ET-1). The objective of the study was to assess possible interplay of the 2 systems in relation to ET-1 in clinical setting. In hypertensive outpatients, on top of typical clinical workup, we assessed ET-1 levels, glucose handling parameters (glycated hemoglobin [HbA(1c)], homeostasis model assessment [HOMA] index, and insulin level), and antioxidative protection (ferric reducing ability of plasma [FRAP], superoxide dismutase [SOD], and vitamin C). Average age of 68 patients (64% women, 50% diabetic, 40% smokers) was 67.7 (10.6) years. Serum ET-1 level averaged 1.09 (0.48) pg/mL and correlated positively with glucose handling-associated parameters (insulin, r = 0.22; HOMA, r = 0.21; HbA(1c), r = 0.23; all Ps < .05) and negatively with constituents of antioxidative protection system (FRAP, r = -0.45; SOD, r = -0.47; both Ps < .0001; vitamin C, r = -0.27; P < or = .01). In sex-, age-, blood pressure-, and creatinine-adjusted models, with interchangeable introduction of antioxidative parameters on top of interchangeable introduction of glucose handling-associated parameters, ET-1 levels were each time only significantly associated with FRAP in the context of HbA(1c); FRAP, SOD, or vitamin C in the context of HOMA; and FRAP or SOD in the context of insulin concentration. In the stepwise regression with the above parameters offered, only FRAP and vitamin C were associated with ET-1 level. In treated hypertensive patients, impaired glucose handling is associated with higher ET-1 levels. This statistical relation is blunted in the context of parameters of antioxidative protection. The hypothesis that poor antioxidation is mediating the effect of impaired glucose handling on ET-1 levels needs further confirmation.

The FGA Thr312Ala polymorphism and risk of intracerebral haemorrhage in Polish and Greek populations.

BACKGROUND AND PURPOSE Spontaneous intracerebral haemorrhage (ICH) is the most fatal form of stroke with the highest morbidity and disability rate of all stroke types. Recent data suggest that the genetic background has a sizeable and mostly undiscovered effect on the brain haemorrhage risk. Since the coagulation system is crucial to ICH pathology, we studied the significance of the FGA Thr312Ala polymorphism in two European populations. MATERIALS AND METHODS We genotyped 550 and 224 controls as well as 261 and 242 stroke patients in Polish and Greek populations, respectively. The ICH diagnosis was confirmed by computed tomography. The FGA Thr312Ala polymorphism was analysed using real-time polymorphism chain reaction. RESULTS Both crude and multivariable regression analyses showed that the studied polymorphism is a protective factor in the Polish population under the dominant and additive models of inheritance. Those results did not replicate in the Greek population. The meta-analysis of results from the Polish and the Greek populations proved that FGA Thr312Ala polymorphism affects the risk of ICH in the dominant model of inheritance. CONCLUSIONS The FGA Thr312Ala polymorphism affects a risk for ICH in the Polish but not in the Greek population. An advanced meta-analysis of well-designed studies with a significant number of cases might provide useful information of novel polymorphisms, including the FGA Thr312Ala polymorphism, and their role in ICH pathology.

Blood Pressure Target: High Time That We Finally Agreed What Is Healthy.

See related article, pp 1110–1114 Over the past 60 years, we learnt not only to appreciate the risk associated with elevated blood pressure (BP), but also to implement efficient therapeutic modalities capable of markedly reducing the risk of cardiovascular complications. However, such seemingly simple matter as deciding the exact therapeutic goals to which BP should be lowered to reduce the risk of events is probably as far from being universally agreed on as it must have been in the fifties. The recent versions of major guideline documents1,2 indicate that for low- to moderate-risk adults <60 years of age, BP should be lowered to <140 mm Hg systolic and <90 mm Hg diastolic. This also applies to patients with coronary artery disease, diabetes mellitus, and chronic kidney disease (Table).1,2 The goal for diastolic blood pressure is <90 mm Hg (<85 mm Hg in diabetes mellitus).2 View this table: Table. Therapeutic Goal for Systolic Blood Pressure in Hypertensive Patients, by Age, Added Risk, and Presence of Frailty However, essential hypertension is to a large extent a disease affecting older adults. It was shown that in this particular group of male patients, the risk of death associated with level of blood pressure raises at ≈160 mm Hg,6 and as further elegantly indicated by Zanchetti et al,7 until recently, there have been no data from randomized clinical trials to indicate that lowering of systolic BP (SBP) to <140 mm Hg could lead to benefit in this subgroup of hypertensive patients.7 The elderly are heterogeneous group, where the ability to cope impacts heavily on survival. Recently, Benetos et al proposed that in the elderly frail patients, the therapeutic goal should revolve about the value …

Subclinical arterial and cardiac damage in white-coat and masked hypertension

Abstract The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima–media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians.