Journal of Human Hypertension (1998) 12, 83–89 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 ORIGINAL ARTICLE Lp(a) in hypertensive patients M Catalano1, E Perilli1, G Carzaniga1, F Colombo2, M Carotta1 and S Andreoni1 1Research Center on Vascular Diseases; 2Department of Internal Medicine, University of Milan, L. Sacco Hospital, Milan, Italy Lipoprotein(a) (Lp(a)) is considered an important risk trations of Lp(a), total cholesterol (TC), triglycerides factor for coronary disease, cerebrovascular pathology (TG) and very low density lipoprotein (VLDL-C) than and re-stenosis of coronary bypass. Few studies have controls (P Ͻ 0.01), with no differences in the plasma been conducted on this lipoprotein in essential arterial concentrations of Lp(a) between the two sexes. Only 10 hypternsive patients. The purpose of our study was to hypertension patients and seven controls had plasma measure the serum concentrations of Lp(a) and the concentrations of Lp(a) of over 30 mg/dl. Lp(a) does not main parameters of the lipid profile in a group of essen- correlate with the main parameters of the lipid profile. tial hypertensive patients not receiving pharmacological We can confirm that hypertension and dyslipidaemia, treatment and with no clinical signs of associated which are two of the main risk factors for vascular dis- pathologies or organ damage. A total of 123 Caucasian eases on an atherosclerotic basis, are often associated. essential arterial hypertensive patients (47 men and 76 However, higher plasma concentrations of Lp(a), albeit women) were studied and compared with 89 controls (36 within the normal range, could be an independent risk men and 53 women) matched in terms of age, sex, body factor for atherosclerosis, and could contribute towards mass index (BMI) and smoking habits. It was found that increasing the incidence of cardiovascular disease in the hypertensive patients had higher plasma concen- people with essential arterial hypertension. Keywords: lipoprotein(a); total cholesterol; apolipoprotein; hypertension Introduction only associated with an increased risk of vascular diseases such as CHD24–31 and the re-stenosis of cor- Many studies have shown clearly that high concen- onary bypass32–35 but are also considered an inde- trations of low-density lipoproteins (LDL-C), Apoli- pendent risk factor for these pathologies. poprotein B (Apo B) and total cholesterol (TC) Up to now there is very little information on Lp(a) accompanied by low concentrations of high-density in hypertensive patients available in the literature, lipoproteins (HDL-C) and Apoprotein AI (Apo AI) and any results published are contrasting.36–41 are the main risk factors for coronary heart disease Therefore, the aim of our study was to measure 1–15 (CHD), and there is considerable evidence that the serum concentrations of lipoproteins, and in all measures which are capable of lowering LDL-C particular of Lp(a) in a group of untreated hyperten- and raising HDL-C concentrations also help to lower sive patients with no clinical signs of associated 16 the incidence of acute events in these patients. In pathologies or organ damage and no family histories patients with essential hypertension there are often of coronary or cerebrovascular atherosclerotic dis- cardiovascular risk factors. Indeed, in these patients, ease. a modification of the lipid profile has been observed, with increased levels of total cholesterol, triglycer- ides and LDL-C and low blood concentrations of Materials and methods 17–19 HDL-C. Patients The lipoprotein(a) Lp(a) was described for the first time in 1963 by Berg.20 It consists of a set of lipopro- A total of 123 Caucasian patients (47 men and 76 teins with different molecular weights (from 350 to women) with essential arterial hypertension [sys- 900 KD),21 in which particles of LDL are bonded to tolic blood pressure (SBP) 165 ± 1.5 mm Hg and apoprotein(a) (apo(a)), which has a kringle structure diastolic blood pressure (DBP) 101 ± 0.4 mm Hg] with a high level of homology to plasminogen.22,23 were studied. Their average age was 53 ± 9 and their The physiological function of this lipoprotein is still average body mass index (BMI) was 25.4 ± 3.9. They unknown but the importance attributed to it has included 14 smokers (11%), but no former smokers. increased considerably in the light of the evidence The diagnosis of essential hypertension was reached that high plasma concentrations of Lp(a) are not after repeatedly measuring the patients’ arterial pressure at different times of the day using a mer- cury sphygmomanometer (Korotkoff sounds I and V) Correspondence: Professor M Catalano, Research Center on Vas- after lying in a supine position for 10 min, consider- cular Diseases, University of Milan, L. Sacco Hospital, Via G.B. Ͻ Ͻ Grassi 74, 20157 Milano, Italy ing an SBP of 140 mm Hg and a DBP of 90 42 Received 22 April 1997; revised 3 July 1997; accepted 5 August mm Hg as normal pressure values. Any patients 1997 with secondary hypertension, a positive family his- Lp(a) in hypertensive patients M Catalano et al 84 tory of cardiovascular diseases, the presence of clini- ations for TC, TG, HDL were: TC 0.8–0.7%, TG 0.7– cally evident cardiovascular (coronary, cerebral, and 0.6% and HDL 1.05–1.32%, respectively. The LDL- peripheral vascular diseases) or tumoral disease; or C and VLDL-C lipoprotein fractions were obtained with electrocardiographic signs of angina, alteration using Friedewald’s formula Apo AI, AII and B were of the S-T segment, changes in T, sugar dysmetabol- determined by means of radioimmunodiffusion ism (fasting glycemia Ͼ110 mg/dl), BMI Ͼ30 kg/m2, (RID), using plates containing polyclonal antibodies disorders of the renal (creatinine Ͼ1.2 mg/dl), liver (Daichi, Tokyo, Japan).46 Lastly, Lp(a) was assayed (AST Ͼ25 IU/L, ALT Ͼ29 IU/L, total bilirubin using two different anti-Apo(a) antibodies, the first Ͼ1.2 mg/dl, ␥-GT Ͼ38 IU/L) or thyroid functions of which was a monoclonal solid-phase antibody, (TSH Ͻ0.5 ␮U/ml or 3.5 ␮U/ml) and uricemia while the second was polyclonal, and marked with Ͼ5.7 mg/dl for the female and Ͼ7 mg/dl for the male a peroxidase (Macra Enzyme Immunoassay kit: patients, were excluded. Terumo Medical Corporation, Strategic Diagnosis Eighty-nine Caucasian subjects (36 men and 53 Division, Elkton, MD 21921, USA).47 The inter- and women) with no clinically evident pathologies and intra-assay coefficients of variations for Lp(a) were originating from the same geographical area were 3.1–1.3%, respectively. The lowest measurable used as a control group. They were matched with Lp(a) concentration was calculated to be 0.8 mg/dl. the hypertensive patients in terms of age (51 ± 3), ± sex, BMI (24.8 3.4) and smoking habits (11 smok- Statistical analysis ers = 12%) (see Table 1). For the purpose of this study, the patients did not receive any drugs capable In order to choose the most appropriate statistical of altering their lipid profiles for at least 4 weeks test, the variables were tested for skewness. Thanks before taking the blood samples. They were given to this preliminary statistical evaluation, it was no dietary restrictions. The hypertensive patients established that, with the exception of Lp(a), all the and the controls all came from Medical Angiology variables in question had a sufficiently normal dis- or Internal Medicine out-patient departments. tribution. For this reason, the statistical analysis was perfor- med using analysis of variance (ANOVA) and Blood samples Tukey’s test, and in view of the skewed distribution The blood samples for determining the apolipoprot- of blood Lp(a) concentrations in the hypertensive ein profiles were taken at 8.00 am, without stasis, and normal subjects we applied the Mann–Whit- by inserting a needle into the vein after fasting and ney test. refraining from cigarette smoking for at least 12 h. The ␹2 test was used for the non-parametric vari- ables. Values of P Ͻ 0.05 were considered signifi- cant. Determination of the apolipoprotein profile The correlations between Lp(a) and all the The samples for determining the plasma concen- remaining parameters studied were checked using trations of total cholesterol, triglyceride, VLDL-C, the Spearman Correlation Test, taking Lp(a) as an LDL-C, HDL-C, Apoproteins AI, AII and B and Lp(a) independent variable. were placed in pre-cooled test tubes containing EDTA (1 mg/ml) and centrifuged immediately at Results 1500 g for 15 min at a temperature of 4°C. The plasma obtained in this way was then frozen and Table 1 describes the main clinical characteristics of stored at −85°C, and assayed within 2 weeks after the essential hypertensive patients and of the nor- sampling. TC and TG were assayed using enzyme mal controls. The two groups were similar in terms methods, with kits supplied by Boehringer of age, sex, smoking habits and BMI, while the aver- (Mannheim, Germany).43,44 The HDL-C concen- age systolic and diastolic BP values were higher in tration was measured after precipitation of the lipo- the patients with essential hypertension. proteins containing Apo B with phosphotungstic Table 2, on the other hand, shows the plasma con- acid and subsequent enzymatic assaying of choles- 45 Table 2 Apolipoprotein profile of normotensives and hyperten- terol. The inter- and intra-assay coefficients of vari- sives Parameters Normotensives Hypertensives P Table 1 Demographic data TC (mg/dl) 204.8 ± 33.1 220.0 ± 38.5 Ͻ0.01b Normotensives Hypertensives TG (mg/dl) 92.6 ± 40.5 128.3 ± 61.9 Ͻ0.01b HDL-C (mg/dl) 46.2 ± 10.7 47.5 ± 10.8 n.s.