Israel Medical Association Journal

Background: Chlorpromazine is a dopamine-receptor antagonist antipsychotic agent. Because of its strong alpha-blocking and sedative actions, it has also been used as emergency therapy for extreme arterial hypertension. Published reports to date have included very small numbers of patients (i.e., 5–30).

Objectives: To analyze data on almost 500 patients who received intravenous chlorpromazine for the emergency treatment of uncontrolled symptomatic hypertension in the pre-hospital setting.

Methods: We reviewed data from 496 consecutive patients who received intravenous chlorpromazine as emergency therapy for uncontrolled symptomatic hypertension. Chlorpromazine was injected intravenously. The dose was 1 mg every 2–5 minutes until the systolic pressure was -<140 mmHg and the diastolic pressure -<100 mmHg with alleviation of symptoms.

Results: The mean dose of chlorpromazine administered was 4.5 +- 5 mg (range 1–50 mg). Only 33 patients (7%) required >10 mg. Chlorpromazine reduced the systolic blood pressure from 222.82 +- 26.31 to 164.93 +- 22.66 mmHg (P < 0.001) and the diastolic blood pressure from 113.5 +- 16.63 to 85.83 +- 11.61 mmHg (P < 0.001). The sinus rate decreased from 97.9 +- 23.5 to 92.2 +- 19.7 beats per minute (P < 0.001). These results were achieved within the first 37 +- 11 minutes.

Conclusions: Intravenous chlorpromazine is safe and effective when used as emergency treatment for uncontrolled symptomatic hypertension.

Objectives: To investigate the effect of low calcium dialysis on post-dialysis hypertension in view of an evident link between serum calcium and blood pressure in both normal renal function and chronic renal failure patients.

Methods: We evaluated 19 chronic hemodialysis patients in whom both post-dialysis hypertension and PDHCa[1] were observed. We investigated changes in serum total calcium, ionized calcium, intact parathormone levels and arterial blood pressure in response to 4 weeks low calcium dialysis as a treatment for PDHCa.

Results: When PDHT[2] patients were treated with low calcium dialysis, post-dialysis blood pressure was significantly decreased compared to pre-dialysis values (155.3 ± 9.7/82.2 ± 7.9 mmHg pre-dialysis vs. 134.1 ± 20.8/80 ± 8.6 mmHg post-dialysis, P = 0.001). Additionally, post-dialysis blood pressure was significantly lower than post-dialysis blood pressure prior to the low calcium dialysis treatment (176.1 ± 15/86 ± 10.8 mmHg post-standard dialysis, 134.1 ± 20.8/80 ± 8.6 mmHg after low calcium dialysis, P = 0.001). A decline in post-dialysis serum calcium (2.34 ± 0.2 vs. 2.86 ± 0.12 mmol/L, P = 0.04) and ionized calcium (1.17 ± 0.12 vs. 1.3 ± 0.06 mmol/L, P = 0.03) compared to pre-dialysis levels was also achieved by this treatment, with no significant changes in iPTH[3] levels.

Conclusions: These data suggest a role for low calcium dialysis in treating acute serum calcium elevation and post-dialysis hypertension in patients receiving maintenance hemodialysis.

Objectives: To examine whether hostility, anxiety and autobiographical memory (a correlate of depression) are associated with IIH[1].

Methods: Using a case-control cross sectional design, 20 patients with IIH were compared with 9 healthy controls of similar age, weight and height, and 11 headache controls. Patients were assessed for hostility and anxiety. The Autobiographical Memory Test was used to assess episodic memories.

Results: The IIH group reported significantly more anxiety and more general episodic memories than the healthy controls, but not the headache control group. The headache control patients reported more general memories than did the healthy controls.

Conclusions: Patients with headaches, whether of general origin or related to IIH, have a poor psychosocial profile. While the study design does not permit any conclusions regarding causality, our results support the need to consider psychological factors in evaluating and treating IIH and headache patients. 

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[1] IIH = idiopathic intracranial hypertension

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder.

Objectives: To perform molecular analysis of a patient with familial PPH[1] and provide her and her family with suitable genetic counseling.

Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling.

Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient.

Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.

Background: Unexplained pulmonary hypertension is assumed to occur mainly in young adults.

Objectives: To describe the features of the disease in older patients and compare them to those in PHT[1] patients of all ages.

Methods: We conducted a retrospective evaluation of the files of patients over 65 years of age in whom UPHT[2] was diagnosed between 1987 and 1999 at two PHT centers serving a population of 4 million. Patients were followed for survival until March 2003. Clinical variables of the study patients were compared to those in PHT patients of all ages.

Results: The study group included 14 patients, 10 females and four males, with a mean age of 70.5 ± 6.7 years. The calculated mean annual incidence of UPHT for the study population was one new case per year per million persons. Seven patients (50%) had systemic hypertension. The mean interval from onset of symptoms to diagnosis was 8.3 months. At diagnosis, 64% of patients had functional capacity of III-IV according to the New York Heart Association classification, and 43% had right heart failure. Mean systolic pulmonary artery pressure was 80 ± 21 mmHg, peripheral vascular resistance 11.7 ± 7 mmHg/L/min, cardiac index 2.16 ± 0.81, and mean right atrial pressure 10.5 ± 5.9 mmHg. Median survival time was 43 months; survival rates for 1 year, 3 years and 5 years were 92.6%, 50%, 40%, respectively. Compared to data from the U.S. National Institute of Health Registry, UPHT in older patients is more common in females, but the incidence as well as clinical, hemodynamic and survival parameters are similar to those in PHT patients at any age.

Conclusions: UPHT occurs in the elderly more frequently than previously thought, with similar features in PHT patients of all ages. The coexistence of systemic and pulmonary hypertension warrants further investigation.

Background: A high total plasma homocysteine level is an independent risk factor for cardiovascular and cerebrovascular disease, but the evidence connecting plasma tHcy level with hypertension is inconsistent.

Objective: To determine the association between plasma tHcy level and some common risk factors for cerebrovascular disease (recurrent  stroke, diabetes mellitus, hypertension, ischemic heart disease and hyperlipidemia) in patients presenting with primary or recurrent acute ischemic strokes.

Methods: This retrospective cross-sectional chart analysis was conducted in a university-affiliated referral hospital. During an 18 month period we identified 113 acute ischemic stroke patients (mean age 71.2), 25 of whom had a recurrent stroke. Plasma tHcy[1] level, obtained 2–10 days after stroke onset, was determined by the high performance liquid chromatography method with fluorescence detection. A multivariate logistic regression model was used to determine the independent relationship between each potential risk factor and tHcy level above or below the 75th percentile.

Results:  Hypertension was more frequent among patients with plasma tHcy level above than below the 75th percentile (51.7% vs. 80.8%, respectively, P = 0.012). After adjusting for demographic and clinical variables, the odds ratio for recurrent stroke and hypertension, with tHcy above or below the 75th percentile, was 3.4 (95% confidence interval 1.01–10.4, P = 0.037) and 4.02 (95% CI[2] 1.2–13.9, P = 0.028), respectively.

Conclusions: A high plasma tHcy level is associated with history of hypertension and recurrent stroke among patients presenting with acute ischemic stroke. These results were independent of other risk factors such as atrial fibrillation, diabetes and hyperlipidemia. Hypertensive stroke patients with hyperhomocysteinemia should be identified as high risk patients as compared to non-hypertensive stroke patients, and may warrant more vigorous measures for secondary prevention.

Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine