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.