Prevalence and Comorbidities of Resistant Hypertension: A Collaborative Population-Based Observational Study.

BACKGROUND: Resistant hypertension, is a clinical condition that may confer high cardiovascular risk. Aim of the observational study was to evaluate the prevalence of resistant hypertension, and the association with cardiovascular risk factors or diseases in the Verona urban area. DESIGN AND METHODS: Eleven family doctors retrieved anonymised data concerning blood pressure, diagnosis of hypertension and treatments from a population of 17,502 adult subjects. The prevalence of resistant hypertension was estimated considering patients who had been consecutively treated with at least four antihypertensive medications, regardless of blood pressure values. Further search concerning the clinical characteristics associated with resistant hypertension was performed in a random subsample of 55 patients. RESULTS: The prevalence of hypertension was 21.9%, that of resistant hypertension was 2.1%, approximately 10% of the whole hypertensive population. High prevalence of diabetes mellitus (53%) and hyperlipidemia (83%) was found in association with resistant hypertension. As for end organ damage, high prevalence of carotid artery stenosis (45%), ischemic heart disease (43%) and left ventricular hypertrophy (40%) was observed in patients with resistant hypertension. Blood pressure was higher than 140/90 mmHg in 58% of patients in spite of treatment with four or more different antihypertensive drugs. The average age, systolic and pulse pressure were significantly higher in the subgroup of patients with resistant hypertension. CONCLUSIONS: Patients with resistant hypertension are characterised by a higher systolic and pulse pressure and a very high attributable cardiovascular risk, due to high prevalence of cardiovascular risk factors and overt organ damage and cardiovascular disease.

Could vitamin D supplements be a new therapy for heart failure? Possible pathogenic mechanisms from data of intervention studies.

Vitamin D deficiency may play a role in the pathogenesis of chronic heart failure (HF), but whether giving patients supplements to raise vitamin D into the normal range improves their survival is not clear. It has been demonstrated that vitamin D deficiency is common in patients with HF, especially the elderly, in obese and in dark skinned people, and that low vitamin D levels are associated with adverse outcome. The epidemiological data have been confirmed by experimental data, which show that knockout mice for the vitamin D receptor developed myocardial hypertrophy and dysfunction. Data from interventional studies are scarce and discordant, and more research is urgently needed to confirm whether add-on supplementation therapy with vitamin D has a role in the management of patients with chronic HF.

Endothelial progenitor cells in patients with severe peripheral arterial disease.

The aims of this study were to investigate the interrelationships between endothelial progenitor cells (EPCs), peripheral arterial disease (PAD), and atherosclerotic risk factors, as only limited data are available regarding the EPCs in patients with PAD. The authors studied the number of EPCs by different methods in a carefully selected group of 45 patients with PAD along with 24 healthy subjects (HS). In patients with PAD, by utilizing the dual-binding method, the number of EPCs was significantly increased compared to HS (M +/- SD, PAD: 73 +/- 33, HS: 52 +/- 20 EPCs/high power field; p < .001). On the contrary, both CD34(+) cell count and CD133(+) cell count were significantly decreased compared to HS. Colony-forming units were significantly increased in PAD compared to HS (median and 25th and 75th percentiles, PAD: 7, 1, 9; HS: 1, 1, 4 CFU/well, respectively; Mann-Whitney, p = .006). In patients with PAD, the number and proliferative activity of circulating EPCs are increased with respect to HS even though EPC count by flourecence-activated cell sorting (FACS) analysis provided different results and this may explain the discrepancy in data collected using different methods. The regulation of the number and biological activity of EPCs in PAD remains unclear.

Forearm haemodynamics, arterial stiffness and microcirculatory reactivity in rheumatoid arthritis.

OBJECTIVES: Cardiovascular disease is the major cause of mortality in patients with rheumatoid arthritis. This work studied the presence of impaired forearm haemodynamics, arterial stiffness and microcirculatory reactivity in young women with rheumatoid arthritis. METHODS: Sixty-five women aged 41-52 years, with rheumatoid arthritis, were screened for the absence of common cardiovascular risk factors. They underwent laser Doppler study on the hand at rest and after ischaemia, endothelium-dependent dilation with colour Doppler ultrasound and pulsewave velocity (PWV). Forty healthy subjects were also examined. RESULTS: Microcirculatory flux at rest with laser Doppler was reduced in rheumatoid arthritis patients (112 +/- 45 versus 220 +/- 65 perfusion units (PU, arbitrary units); P < 0.005), post-ischaemic peak flow was lower in rheumatoid arthritis patients (235 +/- 65 versus 329 +/- 76 PU; P < 0.05); percentage increase in peak flow was higher in rheumatoid arthritis patients compared with healthy subjects (153 +/- 12 versus 65 +/- 18%; P < 0.005). Time to peak flow was longer in rheumatoid arthritis patients (12.7 +/- 8 versus 6.2 +/- 2 s; P < 0.005). Higher microcirculatory resistance was detected in rheumatoid arthritis patients (0.656 +/- 0.011 versus 0.358 +/- 0.009 mmHg/PU; P < 0.05). Endothelium-dependent dilation was impaired in rheumatoid arthritis patients (increase in artery dilation 8.2 +/- 2 versus 11.5 +/- 3%; P < 0.05) and correlated directly with actual C-reactive protein. PWV was higher in rheumatoid arthritis patients (9.3 +/- 0.2 versus 8.4 +/- 0.4 m/s; P < 0.05) and correlated directly with the duration of disease. District resistance by the arm was higher in rheumatoid arthritis patients (1098 +/- 190 versus 661 +/- 55 mmHg/l per minute; P < 0.005). CONCLUSION: Female rheumatoid arthritis patients present with impaired microcirculatory reactivity, endothelial dysfunction and increased arterial stiffness. Alterations in the vascular bed are extended and may explain the increased incidence of cardiovascular events in these patients.

Endothelial progenitor cells in patients with essential hypertension.

OBJECTIVE(S): The eventual role of blood pressure on the endothelial progenitor cell (EPC) has rarely been evaluated and data collected so far relate to patients with co-existing coronary heart disease. METHODS: We have studied the number and functional activity of EPC as well as the number of EPC endothelial colony-forming units (CFU) in a carefully selected group of 36 patients with essential hypertension and 24 normotensive control subjects. RESULTS: In patients with essential hypertension, the EPC number was not statistically different from that found in control subjects (mean +/- SD, essential hypertension 58 +/- 29, controls 53 +/- 20; EPC/high power field). CFU per well were not statistically different in patients with essential hypertension compared with normotensive controls (mean +/- SD, patients with essential hypertension 2.4 +/- 2.6, normotensive controls 3 +/- 3.3 CFU/well). In essential hypertension patients, the EPC number was inversely correlated with both total (R=0.635, P < 0.0001) and low-density lipoprotein (LDL)-cholesterol (R=0.486, P < 0.05). Neither the EPC number nor the EPC CFU were correlated with age, systolic blood pressure, diastolic blood pressure, body mass index, lipoprotein(a), high-sensitivity C-reactive protein or homocysteine. CONCLUSIONS: The present study shows that essential hypertension is not characterized by the altered number or functional activity of EPC. Plasma total and LDL-cholesterol are independent predictors of reduced numbers of circulating EPC in essential hypertension patients. The absence of any correlation between the characteristics of EPC and several markers predictive of cardiovascular damage merits further investigation.

Inflammation and platelet activation in peripheral arterial occlusive disease.

OBJECTIVES: Epidemiological evidence indicates that inflammation accompanies the progression of atherosclerosis. The aim of the present cross-sectional study was to define relationships between platelet activation and inflammation in patients with mild to severe (stages II to IV) peripheral arterial occlusive disease (PAOD) and matched controls. The effect of chronic administration of low-dose acetylsalicylic acid was investigated. METHODS: Subjects were studied on a single occasion. C-reactive protein (CRP) and two indexes of in vivo platelet activation were measured - the urinary excretion of 11-dehydrothromboxane (TX) B(2) by immunoassay and circulating platelet-monocyte aggregates (PMAs) by flow cytometry. RESULTS: Plasma PMAs and urinary 11-dehydro-TXB(2) were significantly increased in PAOD patients compared with controls (P<0.01 for all). A positive correlation between 11-dehydro-TXB(2) and CRP was found in the study population (r(s)=0.63, P<0.001). Using logistic regression analysis, CRP was the only independent correlate of 11-dehydro-TXB(2) (ß(CRP)=11.9, P<0.01), whereas only the presence of PAOD was an independent predictor of high PMA levels (ß(PAOD)=13.7, P=0.001). Chronic administration of acetylsalicylic acid reduced 11-dehydro-TXB(2), but not PMA and CRP. CONCLUSIONS: There is evidence that platelet activation in patients with PAOD is related to the vascular disease and is dependent on the severity of inflammation.

Intralymphocyte magnesium decrease in patients with primary aldosteronism. Possible links with cardiac remodelling.

Our group have described a group of patients with primary aldosteronism which is characterized by significantly decreased intralymphocyte ionized magnesium concentration. Some models of experimental hyperaldosteronism are characterized by cardiovascular fibrosis but despite this fact the link between a negative magnesium balance and fibrosis is lacking. Consequently, to shed some light on the relationships between magnesium and tissue fibrosis we tested the in vitro effects of incubating human fibroblasts in low magnesium medium on mRNA collagen I and III gene expression by northern blot analysis. Both collagen I and III mRNA gene expression were increased by magnesium deprivation. The increase in collagen expression was similar for both collagen I and III. These data are in favour of a potential link between magnesium homeostasis and collagen synthesis. A physiopathologic mechanism linking magnesium homeostasis to the state of collagen turnover may have important clinical correlates such as cardiac remodelling in congestive heart failure.

Glucose-induced alterations of intracellular ionized magnesium in human lymphocytes.

The intracellular ionic content of human erythrocytes may be altered by hyperglycaemia. Despite this, very little is known about the cellular mechanisms linking glucose and cellular magnesium homeostasis. We measured intracellular ionized magnesium in human lymphocytes, by means of a fluorimetric technique, total intracellular magnesium by means of atomic absorption spectrophotometry and intracellular ATP by means of HPLC. The incubation of lymphocytes with D-glucose in the absence of insulin was followed by a significant decrease in intracellular ionized magnesium; this effect did not occur when the cells were incubated with L-glucose. The effect of glucose on intracellular ionized magnesium was blocked by amphotericin B and the EC(50) of the effect of glucose on intracellular ionized magnesium was about 5 mmol/l of glucose. The increase of intracellular ionized magnesium in cells incubated in the absence of glucose was followed by a decrease in intracellular ATP. In a Na(+)-free medium the decrease of intracellular ionized magnesium in the presence of glucose was still present and the incubation of lymphocytes with glucose did not modify total intralymphocyte magnesium. By selective permeabilization of cell membranes, we established that glucose could not increase compartmentalized intracellular ionized magnesium. Our data supports the hypothesis that glucose per se induces a substantial decrease in intracellular ionized magnesium, which is probably due to an augmented binding of intracellular ionized magnesium to cellular ATP.

Collagen I and III mRNA gene expression and cell growth potential of skin fibroblasts in patients with essential hypertension.

OBJECTIVES: Despite the claimed disregulation of extracellular matrix synthesis and the increased proliferation rate of different cell types in experimental models of hypertension, very few data are available on collagen synthesis and the proliferation rate of fibroblasts in essential hypertensive patients. DESIGN: We measured collagen I, collagen III, histone H3 mRNA gene expression, collagen protein concentration and thymidine incorporation in fibroblasts from 17 essential hypertensive patients (EH) and 13 healthy normotensive control subjects (NC). METHODS: A Northern blot analysis was performed on fibroblasts in culture obtained from skin biopsies. Collagen protein concentration and DNA synthesis were measured by means of incorporation of tritiated proline and tritiated thymidine, respectively. RESULTS: In cultivated fibroblasts from hypertensives, the expression of collagen III mRNA after addition of fetal calf serum was significantly increased in comparison with that of normotensive-derived cells. After addition of fetal calf serum, collagen protein was statistically increased in cultures from EH patients as compared to NC. In hypertensives, the expression of histone H3 mRNA as well as tritiated thymidine incorporation were both increased as compared to normotensives. CONCLUSIONS: Our data suggest that cultivated fibroblasts from essential hypertensive patients are characterized by an increased expression of type III collagen mRNA and collagen protein synthesis in response to fetal serum, as compared to normotensive-derived cells. Cells from hypertensives are characterized by an increased rate of proliferation after addition of fetal serum, as ascertained by increased thymidine incorporation and increased histone H3 mRNA gene expression, as compared to normotensive-derived cells. This phenotype could be genetically determined and may have an important role in the pathogenesis of essential hypertension.