Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo.

AIMS: A randomized, double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation (not due to haemodynamic alternations) to sinus rhythm, and for rate control in converters and non-converters was set up. Outcome measures were conversion within 12 h; time to conversion; early rate control; and stable slowing within 12 h. METHODS: We studied 40 patients with recent onset (< 1 week) atrial fibrillation; controls received saline intravenously, the other patients digoxin 1.25 mg. RESULTS: One patient converted before digoxin administration. Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo (ns). The mean time to conversion tended to be shorter only for digoxin. Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters (P < 0.05). For all patients on digoxin, heart rate after 30 min was lower compared to baseline (P < 0.002) and to placebo (P < 0.02). Persistent, stable slowing occurred only in 3/10 non-converters on digoxin (P < 0.05), and two patients developed bradyarrhythmias. QTc was shortened immediately after conversion in all patients. Converters had baseline characteristics similar to those of non-converters. CONCLUSIONS: Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion, and provides weak rate control.

MN blood group, a genetic marker for essential arterial hypertension in young adults.

The MN blood group has been linked with blood pressure levels and sodium-lithium counter-transport in red blood cells of normotensives. The aim of the study was to compare the distribution of MN phenotypes according to age at diagnosis of essential hypertension and to investigate the relationship between MN phenotypes, severity of complications and therapeutic needs. MN blood group polymorphism was studied in 386 Caucasians with established essential arterial hypertension, treated for at least one year. In 285 healthy normotensive blood donors, blood pressure was measured and MN blood group was typed. MN blood groups were typed with polyclonal antisera and confirmed with monoclonal antisera. MN blood group phenotype frequencies in hypertensives were 0.207 (MM), 0.601 (MN), and 0.192 (NN), which differs (P < 0.000002) from the distribution in the controls: 0.270 (MM), 0.540 (MN) and 0.189 (NN). The relative MN phenotype frequency was strongly over-represented (P < 0.05). Age at detection of hypertension was significantly lower for MN patients (P < 0.0005). With increasing age of detection, the relative frequency of MN phenotype gradually decreases from 0.73 in those detected before age 40 to 0.50 for patients detected after 60. This observation holds true for both male and female hypertensive. Furthermore, hypertensives with a MM blood group had a lower (P < 0.05) prevalence of cerebrovascular accidents. In controls, blood pressure was comparable for the three MN phenotypes. The present study suggests that the MN phenotype is a genetic factor associated with early detection of essential hypertension.

Refractory hypertension is associated with the haptoglobin 2-2 phenotype.

BACKGROUND: Many cases of refractory hypertension cannot be attributed to specific identifiable factors. Haptoglobin polymorphism has been suggested as a candidate genetic marker in essential hypertension. The aim of this study was to investigate the distribution of haptoglobin types in patients with refractory hypertension. METHODS: Haptoglobin polymorphism was studied in 383 patients with non-refractory and 62 patients with refractory hypertension. Haptoglobin was typed using starch gel electrophoresis of haemoglobin-supplemented serum. RESULTS: In the group of patients with refractory hypertension, the relative allele frequency of haptoglobin 1 (0.266) was lower than in the group with non-refractory hypertension (0.385: P < or = 0.05). The relative frequency of haptoglobin 2-2 was 39% in the non-refractory compared with 56% in the refractory group (P < or = 0.05). In the latter group, the relative frequency of haptoglobin 2-2 was highest (75%) in patients requiring medication with four classes of drug. CONCLUSION: Hypertension patients with the haptoglobin 2-2 phenotype are at higher risk of developing refractory hypertension than those with other haptoglobin phenotypes.

Haptoglobin polymorphism and complications in established essential arterial hypertension.

OBJECTIVE: Salt sensitivity and the magnitude of systolic blood pressure have been linked to haptoglobin (Hp) polymorphism in normotensives. The aim of the present study was to investigate the indices of hypertension, the severity of complications and the occurrence of coronary and peripheral artery disease for the various haptoglobin phenotypes and their relation to the therapeutic needs (number and class of drugs) of established arterial hypertensives. DESIGN: Haptoglobin polymorphism was studied in 302 Caucasians with established essential arterial hypertension who had been treated for at least 1 year. METHODS: Haptoglobin polymorphism was studied using starch-gel electrophoresis of haemoglobin-supplemented serum. RESULTS: The relative allele frequencies of Hp 1 and Hp 2 (0.036 and 0.640, respectively) in established hypertensives were comparable with those of the control population. Logistic regression analysis confirmed that Hp 2-2 contributes to the therapeutic needs in hypertension. The most important factors determining therapeutic needs were coronary artery disease, Hp 2-2 phenotype, body mass index (BMI) and left ventricular hypertrophy. Although no contributive effect of serum haptoglobin concentration could be derived from the logistic regression approach, analysis of serum haptoglobin concentration demonstrated a concentration-related effect on therapeutic needs for the Hp 2-2 phenotype only. CONCLUSIONS: The present study suggests that hypertensives with an Hp 2-2 phenotype need more complex combinations of antihypertensive drugs to reduce blood pressure to the same level. The hypertensive patient carrying Hp 2-2 is more likely to accumulate atherosclerotic lesions of the coronary or peripheral arteries, despite comparable lipid levels, smoking habits and BMI. Hp 1-1 patients are characterized by a younger age at diagnosis and a lower complication rate. In view of the greater therapeutic needs and the higher complication rate, Hp 2-2 hypertensives need more careful follow-up.