Cardiovascular hypertensive emergencies.

Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

Masked hypertension unfavourably affects haemostasis parameters.

OBJECTIVE. Recent evidence demonstrates that masked hypertension (MH) is a significant predictor of cardiovascular disease. The aim of our study was to examine the impact of MH on haemostasis parameters and to compare the findings to those of healthy normotensives matched for age, sex, body mass index and the rest of risk factors. DESIGN AND METHOD. 130 (60 male, 70 female) healthy subjects mean age 45 ± 12 years who had clinic blood pressure < 140/90 mmHg were studied. The whole study population underwent 24-h ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (eight males, 16 females) had MH (daytime systolic blood pressure ≥ 135 mmHg or daytime diastolic blood pressure ≥ 85 mmHg - group A) and the remaining 106 subjects (52 males, 54 females) had normal ABPM recordings - group B. Fibrinogen, thrombomodulin ™, the antigens of plasminogen activator inhibitor 1 (PAI-1Ag) and tissue plasminogen activator (tPA-Ag) were determined in the two groups. Results. The PAI-1 Ag, tPA-Ag, fibrinogen and TM levels were significantly higher in the masked hypertensive group than to normotensive control group. CONCLUSIONS. Our findings suggest that subjects with MH have significantly higher fibrinogen, TM, PAI-1Ag and tPA-Ag plasma levels compared with normotensives. This observation may have prognostic significance for future cardiovascular events in subjects with MH and needs further investigation.

Changes of metalloproteinases profile in patients with masked hypertension.

INTRODUCTION: The aim of our study was to investigate whether collagen degradation is altered in participants with masked hypertension and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration and to compare the findings with those participants with normal blood pressure levels matched for age, sex, and body mass index. METHODS: Twenty-four (11 men, 13 women) participants with masked hypertension [mean age 46 +/- 7 years and body mass index 25.9 +/- 2.1 kg/m(2) (group A)] and 106 healthy normotensives (49 men, 57 women) with normal blood pressure [mean age 44 +/- 6 years and body mass index 25.5 +/- 2.4 kg/m(2) (group B)]. RESULTS: The plasma levels of matrix metalloproteinase-9 were significantly higher, while the levels of tissue inhibitors of metalloproteinases-1 and -4 were significantly lower in group A compared with group B (matrix metalloproteinase-9: 569 +/- 135 vs. 282 +/- 117 ng/mL, TIMP-1: 169 +/- 42 vs. 230 +/- 37 ng/mL, P < .01, and TIMP-4: 2.1 +/- 1.3 vs. 4.2 +/- 1.98 ng/mL, P < .04, respectively). CONCLUSIONS: Patients with masked hypertension had significantly increased matrix metalloproteinase-9 plasma levels and significantly decreased plasma levels of tissue inhibitors of metalloproteinases-1 and -4 compared with participants with normal blood pressure. These findings need further investigation.

Antiendothelial cell antibody levels in patients with masked hypertension.

UNLABELLED: Recent evidence demonstrate that masked hypertension (MH) is a significant predictor of cardiovascular disease, while, elevated levels of circulating antibodies against endothelial cell surface antigens (antiendothelial cell antibodies - AECA) seem to play an important role at the early stages of atherosclerosis process and of borderline hypertension as well. Aim of this study was to investigate the presence of AECA in patients (pts) with MH and to compare the AECA title among pts with MH and healthy normotensives (HN), matched for age, sex and body mass index. METHODS: One hundred-thirty (60 M, 70 F) healthy subjects mean age 45+/-12 yrs who had clinic blood pressure <140/90 mm Hg were studied. The whole study population underwent 24 hour ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (8 M, 16 F) had MH (daytime systolic blood pressure >/=135 mm Hg or daytime diastolic blood pressure >/=85 mm Hg - group A) and the remainder 106 subjects (52 M, 54 F) had normal ABPM recordings, group B. IgG and IgM AECA levels were determined by ELISA method. AECA levels were expressed as mean value+/-SD. None of the study population had a history of connective tissue disease or any metabolic disorder. RESULTS: Significantly increased titles of AECA class IgG were found in 8/24 pts of group A (30%) vs. 5/106 (4.6%) of group B (p<0,001). Significantly increased titles of AECA class IgM were also found in 6/24 pts of group A (25%) vs. 3/80 (3.8%) of group B (p<0,001). CONCLUSIONS: Our results suggest that patients with MH have significantly higher AECA levels of both classes (IgG, IgM) compared to healthy normotensives. These findings may indicate a possible explanation of the increased cardiovascular risk in MH. The possibility that high AECA levels may be a driving mechanism for the development of MH needs further investigation.

Clinical significance of matrix metalloproteinases activity in acute myocardial infarction.

Matrix metalloproteinases (MMP) degrade myocardial fibrillar collagen in acute myocardial infarction (MI) patients. Their activity is tightly controlled in normal myocardium by a family of closely related tissue inhibitors known as TIMP. An imbalance in their activity might contribute to post-MI remodeling. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured, using relevant ELISA kits, in 24 (22 males-2 females), acute MI patients with a mean age 59 +/- 14 years. Blood samples were taken on admission (0 h), and 3 h, 6 h, 9 h, 18 h, 24 h, 36 h, 48 h, 3rd, 4th, 5th, 7th, 15th, 30th days after MI. All patients underwent coronary arteriography with ventriculography for estimation of left ventricular ejection fraction (LVEF) and extent of coronary artery diseases, and echocardiographic study for measuring end-diastolic diameter (EDD). Ten patients with an LVEF < 45%, an EDD > 47.5 mm, and heart failure symptoms were included in group A and compared against 12 patients with an LVEF > 45% an EDD < 47.5 mm in group B. Mean plasma concentrations of MMP-1 were higher by 21% in group A (1.3 +/- 0.2 ng/mL) compared to group B (1 +/- 0.1 ng/mL) over the total study period. TIMP-1 plasma concentrations showed very little difference between the 2 groups, (704 +/- 213 ng/mL versus 691 +/- 165 ng/mL, (6%)). Finally, plasma concentrations of MMP-1/TIMP-1 complex were lower by -36% in group A with a mean value of 2.7 +/- 0.6 ng/mL versus 3.7 +/- 0.5 ng/mL in group B. Mean values for the differences were significant at time points 0, 6, 18, 24 and 48 hours for MMP-1 (p < 0.036), and on 48 h and the 4th day for MMP-1/TIMP-1 complex (p < 0.031). Moreover, a good correlation was found between plasma concentrations of creatine kinase (CK) and MMP-1 at 18 h (r = 0.422, p = 0.041) and on the 4th day (r = 0.67, p = 0.046), and TIMP-1 on the 4th day (r = 0.67, p = 0.047). Additionally, mean values for LVEF were 35.8 +/- 8.8% in group A versus 51.2 +/- 1.8% (p = 0.00014) in group B. Also, the EDD in-group A was 52.1 +/- 6.9 mm versus 42.9 +/- 3.2 mm in group B (p = 0.00013). In acute MI patients, increased MMP-1, with no change in TIMP-1, is associated with left ventricular dysfunction and dilatation, suggesting that increased collagenolytic activity contributes to loss of LV function.

Eprosartan effect on fibrinolytic/hemostatic variables in arterial hypertension: a comparative study to losartan.

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system predisposing to a procoagulant state. The aim of the present study was to examine the comparative efficacy of the angiotensin II type 1 receptor antagonists eprosartan and losartan on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensive patients. A total of 86 patients whose hypertension was controlled by monotherapy with eprosartan 600 mg (45 patients) or losartan 100 mg (41 patients) were studied. The plasma levels of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator inhibitor (tPA) antigen, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI) antigen, and fibrinogen were determined before and after 6 months of therapy. Age, sex distribution, body mass index, lipid profile, systolic and diastolic blood pressure levels, and baseline values of the measured markers were similar in both groups. After 6 months of therapy, systolic blood pressure was significantly lower in patients treated with eprosartan, while no differences were observed with respect to diastolic blood pressure. Treatment with both drugs was associated with a significant decrease in PAI-1 antigen, TM, fibrinogen plasma levels and an increase in tPA antigen. The favorable modification of all the above parameters was significantly greater in the eprosartan than in the losartan group, while TFPI plasma levels were decreased to a similar extent with both drugs. In conclusion, the results of our study indicate that 6-month monotherapy with a new angiotensin II type 1 receptor blocker, eprosartan, is associated with a more favorable modification of hemostatic/fibrinolytic status than with losartan.

Effect of angiotensin-converting enzyme inhibitor on collagenolytic enzyme activity in patients with acute myocardial infarction.

Matrix metalloproteinases and their tissue inhibitors are key enzymes degrading myocardial collagen in acute myocardial infarction (AMI). The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) influence collagenase-1 (MMP-1) and their tissue inhibitor (TIMP-1) activity in AMI patients. Plasma levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured in 24 patients (aged 58.4 +/- 13.9 years) with AMI. Thirteen patients received perindopril 4 mg/day (group A) and 11 did not (group B). Plasma samples collected on admission and at 0, 3, 6, 9, 12, 18, 24, 36 and 48 hours and on days 3, 4, 5, 7, 15 and 30 thereafter were analyzed by relevant ELISA kits. Ejection fraction (EF) was assessed by ventriculography and end-diastolic diameter (EDD) echo-study on days 6 and 30. Values of collagenolytic enzymes of group A compared with those in group B were on average lower by 34%, 18.3% and 40%, respectively. The difference in values between groups at 0 h, 3 h and 9 h was significant (p < 0.048). ANOVA repeated measurement analysis showed significance within subjects for MMP-1 alone (p < 0.043) and for MMP-1 and ACEI (p < 0.046), while for TIMP-1 and MMP-1/TIMP-1 complex significance was only p < 0.0009. Regarding EDD changes, patients in group A showed minimal or no changes (51.23 +/- 1.8 mm to 51.6 +/- 2.13 mm), their EF was 38.8% and infarct size was medium to large. In contrast, group B showed a trend to increase EDD (41 +/- 0.78 mm to 42.33 +/- 0.59 mm), their EF was 50.5% and infarct size was small to medium. In conclusion, early initiation of ACEI treatment reduces collagenolytic activity. This effect may be considered an alternative mechanism for beneficial effects on postinfarction remodeling.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Predicting response to chronic antihypertensive treatment with fosinopril: the role of angiotensin-converting enzyme gene polymorphism.

Insertion (I)/deletion (D) polymorphism of the ACE gene has been reported to be involved in various cardiovascular diseases. We investigated prospectively whether the response to the ACE inhibitor fosinopril varied according to the ACE genotype in previously untreated Greek hypertensive patients. After a 4-week observation period, fosinopril was administered at a dose of 20 mg daily and blood pressure was measured weekly for 6 months. The study population consisted of 104 hypertensive patients (46 male, 58 female). There were no differences in age, gender, body mass index, and pretreatment blood pressure levels among patients with the DD, ID, and II genotypes (n= 42, 30, 32, respectively). The reduction in systolic blood pressure was significantly greater in patients carrying the DD compared to II or ID genotypes (5.6 +/- 3.1 vs. 3.1 +/- 1.1 or 3.6 +/- 2.2, respectively; ANOVA, p < 0.05). The reduction in diastolic blood pressure was also significantly greater in DD hypertensives compared with II or ID (8.9 +/- 6 vs. 5.5 +/- 3.4 or 5.8 +/- 4, respectively; ANOVA, p < 0.05). The age and BMI were not correlated with the changes in SBP or DBP that were observed after fosinopril administration. In conclusion, the ACE gene genotype was shown to influence the response to fosinopril in hypertensive patients.

Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol.

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.

Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension.

This study was designed to investigate both resistance to activated protein C (APC-R) and the factor FV Q506 mutation incidence in patients with a history of acute myocardial infarction (AMI) and patients with primary hypertension (PH), a high-risk group for arterial thrombosis. Eighty patients with a history of AMI (group A), 160 patients with a history of PH (group B), and 124 age-matched controls without arterial disease (group C) were studied. APC-R was determined using the Coatest APC Resistance Kit of Chromagenix, Sweden. The prevalence of the FV Q506 mutation was estimated by DNA analysis (Bertina method). The prevalence of the FV Q506 mutation was 20%, 13.75%, and 8% in groups A, B, and C, respectively (A v C P = .0466). The prevalence of APC-R was 47.5% in group A v 13% in group C (P < .0001) and 36.25% in group B v 13% in group C (P < .0001). The response to activated protein C expressed as mean value +/- SD was 2.05 +/- 0.33 in group A v 2.56 +/- 0.46 in group C (P < .05) and 2 +/- 0.22 in group B v 2.56 +/- 0.46 in group C (P < .05). These findings suggest that patients with a history of AMI or PH have a significantly increased incidence of both APC-R and FV Q506 mutation compared with the control group. These findings support the hypothesis that these anticoagulant defects may be risk factors for arterial thrombosis.

Elevated plasma immunoreactive leptin levels preexist in healthy offspring of patients with essential hypertension.

BACKGROUND: Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH. METHODS AND RESULTS: Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively). CONCLUSIONS: Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.

Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 levels in patients with essential hypertension.

Increased sympathetic activity seems to play an important role in the pathogenesis and development of complications of atherosclerotic origin in patients with essential hypertension (EH). The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE. Fifty-eight patients (32 M, 26 F) with EH and microalbuminuria, with a mean age of 56.6 +/- 8.2 years and a body mass index (BMI) of 23.8 +/- 3.1 kg/m2 who responded to M therapy (0.3-0.4 mg/daily) were studied before and after their blood pressure control. The 24-hour urine albumin excretion (RIA method), as well as TM and PAI-1 plasma levels (ELISA method), were determined before and 6 months after the initiation of treatment under moxonidine therapy. At the end of the 6-month period, all patients remained normotensive. The 24-hour urine albumin excretion had decreased to 24.5 +/- 6.4 vs. 32.3 +/- 7.2 ug/min before therapy (P < 0.001). The plasma TM levels had decreased to 44.0 +/- 7 vs. 51.0 +/- 9 ng/mL before therapy (P < 0.01), and PAI-1 levels had also decreased to 11.5 +/- 4.5 vs. 15.8 +/- 8 IU/mL before therapy (P < 0.05). The results of our study suggest that in hypertensive patients with microalbuminuria, moxonidine, an imidazoline I1-receptor agonist, a new centrally acting antihypertensive agent, significantly reduces urine albumin excretion as well as thrombomodulin and PAI-1 levels. These preliminary findings demonstrate a favorable effect on renal function and endothelial homeostatic mechanisms (maintenance of haemostatic balance).

Haemostasis balance disorders in patients with essential hypertension.

This study was aimed at investigating haemostasis parameters in patients (pts) with arterial hypertension (AH) before any medical treatment and to correlate these findings with those in healthy normal Greek population 83 pts (48 m, 35 w) mean age 49.8 +/- 10.1 yrs, body mass index 23.4 +/- 1.5 with mild to moderate AH and 42 healthy volunteers matched for sex (24 m, 18 w), age 51.2 +/- 10.5 yrs and body mass index 22.8 +/- 1.46 were studied. Fibrinogen, vWF, plasminogen, ECLT, a2 antiplasmin, tPA-Ag, PAI-1 in all pts and in the control group were measured. Mean age and BMI did not significantly differ between the two groups. The hypertensive patients had significantly higher levels of fibrinogen (327.75 +/- 51.36 vs. 272.84 +/- 46.8 mg/dl), tPA-Ag (8.81 +/- 3.32 vs. 5.76 +/- 2.54 ng/ml) and PAI-1 (11.8 +/- 10.9 vs. 7.91 +/- 5.5 IU/ml), whereas a2 antiplasmin level was significantly lower (98.71 +/- 15.40 vs. 107.84 +/- 17.52%). No differences were found between hypertensives and normal subjects in vWF, plasminogen and ECLT. These preliminary data suggest that in pts with mild to moderate AH, before any medical treatment, there are significantly higher levels of fibrinogen, tPA-Ag and PAI-1 compared with normal volunteers, whereas there are significantly lower a antiplasmin levels. These findings indicate a disturbance in the haemostasis balance with hypercoagulability and fibrinolytic deficiency.