Lipoprotein(a) levels in centenarians

In elderly subjects (above 65 years), cardio- and cerebrovascular diseases are known to contribute to the death rate. Serum lipoprotein(a) = Lp(a), a low density lipoprotein, is involved in the atherogenic processes, as confirmed by several clinical trials. We evaluated serum Lp(a) levels in a group of centenarians (15 females and 7 males, mean age 102.81 +/- 2.5 years) compared to 25 healthy control subjects (10 males and 15 females, mean age 51.12 +/- 15.34 years). In all subjects Lp(a) serum levels were determined by ELISA method (EIA mod. 2550 reader). Statistical analysis of the results was performed by using the Student's t test. In centenarians the mean Lp(a) level increased (39.6 +/- 23.53 mg/dl) compared to that of the control group (16.78 +/- 16.24 mg/dl) (p < 0.005). The elevated Lp(a) values observed in centenarians may be attributed to the presence of low molecular weight lipoprotein isoforms which are known to be associated with cardio-cerebrovascular risk. Therefore, it seems that elevated Lp(a) levels alone are not risk factors for the onset of acute acute vascular accidents and do not influence longevity.     

Haemostatic and rheological changes in normal pregnancy and pre-eclampsia

Platelet activity (microaggregate formation, ADP-aggregation and beta-thromboglobulin release), coagulation activity (fibrinogen level and factor VIII related antigen/coagulant activity), and rheological factors (plasma viscosity, whole-blood viscosity and erythrocyte deformability) were studied serially in 14 healthy pregnancies to determine the effect of gestational age. Fourteen patients with pre-eclampsia, each matched for stage of gestation with a normal pregnancy, showed normal rheology of circulating blood and normal aggregability of circulating platelets, but there was a significant increase in platelet release of beta-thromboglobulin and a shorter platelet production time, indicating a shorter life-span. The results suggest that localized platelet activation within the utero-placental microvasculature, rather than a rheological abnormality, is a likely contributory factor to the occlusive vascular lesion of pre-eclampsia and fetal growth retardation.     

Skin capillary density changes in normal pregnancy and pre-eclampsia

BACKGROUND: Many abnormalities are known to occur in the microcirculation in essential hypertension, including reduction in capillary density or rarefaction. Peripheral vasodilatation and angiogenesis are critical components of the physiological adaptation in normal pregnancy. OBJECTIVE: To investigate the hypothesis that defective angiogenesis, reflected in capillary rarefaction, may be implicated in the clinical syndrome of pre-eclampsia. METHODS: We used intravital capillary video-microscopy to study functional (baseline) and structural (after maximization with venous congestion) skin capillary density in 22 healthy normotensive pregnant women and compared our findings with those in 22 non-pregnant age-matched healthy controls and 11 women whose pregnancies were complicated by pre-eclampsia. RESULTS: We found that both functional and structural capillary density increased during normal pregnancy. Capillary density in pre-eclamptic women was significantly lower both at baseline and after maximization. Skin capillary density appeared to be inversely correlated with blood pressure during pregnancy and in pre-eclampsia. CONCLUSIONS: A low capillary density may account, in part, for the failure of blood pressure to decrease in pre-eclamptic pregnancies, and may reflect the maladaptive cardiovascular response that is part of the pre-eclampsia syndrome.     

Lipoprotein (a) levels, apolipoprotein (a) phenotypes and thyroid autoimmunity

It has been reported that euthyroid normolipidemic males and postmenopausal females exhibit significantly higher serum lipoprotein (a) (Lp(a)) levels compared with age- and sex-matched normolipidemic controls. However, it is well known that there is an inverse correlation between Lp(a) concentration and apolipoprotein (a) (apo(a)) isoform size. Thus, it is imperative to exclude differences in apo(a) isoform frequencies between subjects with or without thyroid autoimmunity in order to verify if there is an association between thyroid autoimmunity and increased Lp(a) concentration. To exclude such an effect of different apo(a) isoform frequencies, we determined apo(a) phenotypes in 22 patients (9 males and 13 postmenopausal females) with thyroid autoimmunity and in 64 (29 males and 35 females) age- and sex-matched individuals without thyroid autoimmunity (control group). There were no significant differences in the values of lipid parameters between the two groups, including Lp(a). We did not detect any significant differences in the apo(a) phenotype frequencies between the two groups. Additionally, in neither of the subgroups formed according to the presence of low molecular vs high molecular weight apo(a) isoforms were there any significant differences in median serum Lp(a) levels between patients with and without thyroid autoimmunity. Thus, our results contradict the previously reported association between thyroid autoimmunity and Lp(a) concentrations.     

Lipoprotein(a) levels in the nephrotic syndrome.

We investigated serum lipoprotein(a) [Lp(a)] levels in 20 patients with the nephrotic syndrome. Lp(a) levels in the nephrotic syndrome patients were significantly higher than those in a control group (30.4 +/- 22.5 vs 10.4 +/- 17.7 mg/dl). Overall, the serum Lp(a) and lipid levels showed no relationship, but on an individual basis the serum Lp(a) level varied with the serum levels of total cholesterol and low density lipoprotein cholesterol in the nephrotic syndrome patients. Our findings suggest that a decrease in serum albumin led to increased hepatic Lp(a) synthesis. It is well known that thrombotic disease supervenes on hypercoagulability in the nephrotic syndrome, so the determination of Lp(a) levels in these patients may provide information which is useful for preventing thrombotic complications.     

Plasma atrial natriuretic factor levels during normal pregnancy and pregnancy complicated by diabetes mellitus and hypertension

Atrial natriuretic factor (ANF) may play a role in the regulation of the changes of blood volume and vascular reactivity during pregnancy and when pregnancy is complicated by hypertension. Reports of plasma ANF levels during pregnancy are conflicting. We have prospectively studied plasma ANF levels during pregnancy in 25 women, and compared these with 20 age-matched non-pregnant women. Five women developed hypertension during pregnancy and a further five who remained normotensive had insulin-dependent diabetes mellitus. Plasma ANF was 6.8 +/- 1.2 (mean +/- SEM) and 6.3 +/- 0.9 pmol/l during weeks 8-15 and 24-31 of normal pregnancy (n = 15; vs non-pregnant levels (4.0 +/- 0.6 pmol/l) P less than 0.05, n = 20). Levels were 4.3 +/- 0.8 and 3.9 +/- 0.4 pmol/l during weeks 16-23 and 32-39. In the diabetic patients and in the group who developed hypertension levels were at no time different from the uncomplicated pregnancy group. Serum aldosterone increased as pregnancy progressed, but plasma renin activity remained unchanged. As plasma ANF was not different between those who did, and those who did not develop hypertension, early measurement of it will not predict who will and who will not develop hypertension during pregnancy.     

A longitudinal study of resting peripheral blood flow in normal pregnancy and pregnancies complicated by chronic hypertension and pre-eclampsia

Objectives: To investigate the hypothesis that reduced resting tissue blood flow precedes the clinical onset of pre-eclampsia in women at risk of the disease. METHODS: We used venous occlusion plethysmography to compare resting calf muscle blood flow in 18 normal pregnant controls, 18 pregnant women with chronic hypertension, and 23 pregnant women at increased risk of developing pre-eclampsia. Calf blood flow was measured at 16, 20, 24, 28, 32 and 36 weeks of gestation. RESULTS: Blood flow increased with gestation in normal pregnancy (P = 0.004) and chronic hypertension (P = 0.006), but not in the 'at risk' women who did not develop pre-eclampsia (P = 0.36). In contrast, blood flow decreased significantly in eight out of the 23 women 'at risk', who developed pre-eclampsia (P < 0.00001, ANOVA). The decrease in flow preceded the clinical diagnosis of the pre-eclampsia by several weeks. Moreover, a significant inverse correlation was observed between resting blood flow and plasma uric acid concentrations (r = -0.86, P = 0.03) in the women that developed pre-eclampsia. CONCLUSIONS: We have shown that reduced resting blood flow precedes the clinical onset of pre-eclampsia independently of hypertension per se. These findings support the notion that impaired tissue blood flow may be involved at an early stage in the pathophysiology of the disease.     

Evaluation of kisspeptin levels in obese pregnancy as a biomarker for pre-eclampsia

Objectives Circulating concentrations of the peptide kisspeptin have been proposed as a novel biomarker for early detection of pre‐eclampsia. Our aims were to assess analytical and clinical performance characteristics of a commercial kisspeptin assay and to determine sensitivity and specificity of the test for pre‐eclampsia. Design Prospective, longitudinal study in a United Kingdom tertiary referral Antenatal Metabolic Clinic. Patients Severely obese (body mass index, BMI > 40kg/m², n = 194) and lean (BMI < 25kg/m², n = 78) pregnant women. Measurements A commercial kisspeptin ELISA (Phoenix Pharmaceuticals) was assessed for analytical sensitivity, specificity, precision, linearity, recovery and stability in maternal plasma samples at 16, 28 and 36 weeks gestation. Pre‐eclampsia, defined using International Society for the Study of Hypertension in Pregnancy guidelines; blood pressure; delivery gestation; birthweight. Results Kisspeptin concentrations were lower in early pregnancy in obese women (P < 0·001), and in women who later developed pre‐eclampsia (P < 0·05), compared with women with uncomplicated pregnancies. For 16‐week plasma kisspeptin in prediction of pre‐eclampsia, area under the receiver‐operator characteristic curve was 0·80 (P < 0·01), positive and negative likelihood ratios were 3·0 and 0·2, and test sensitivity and specificity were 85·7 and 71·4%, respectively. In regression analyses, kisspeptin (16 weeks) associated positively with delivery gestation (P < 0·05) and birthweight (P < 0·0001), and negatively with 28‐ and 36‐week blood pressure (P < 0·0001). Conclusions Kisspeptin concentration in early pregnancy is a promising biomarker for pre‐eclampsia and low birthweight but cannot be recommended, in isolation, for universal screening because of inadequate test sensitivity and specificity. Large‐scale studies are required to assess its potential in a panel of biomarkers.     

Apelin levels in normal pregnancy

Objective Apelin is an adipokine secreted from adipose and other tissues with increased expression in obesity, role in glucose metabolism and atherosclerosis, as well as in oxidative stress. Pregnancy is considered a state of hyperlipidemia, oxidative stress and decreased insulin sensitivity. The aim of the present study is to investigate the levels of apelin in human pregnancy and its relation to insulin sensitivity. Patients and measurements One hundred and six pregnant women (24th–28th week of gestation), aged 27·9 ± 0·4 years, were compared to 106 age‐matched healthy, nonpregnant women (controls). Measured parameters included serum levels of glucose, insulin, apelin, adiponectin, total cholesterol, high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL), triglycerides and oxidized LDL (ox‐LDL). The body mass index (BMI) and the quantitative insulin sensitivity check index (QUICKI) were calculated as well. Results BMI, serum lipids and insulin levels were significantly higher, whereas serum apelin and glucose levels were lower in the pregnancy group compared to the control group. There was a significant negative correlation between apelin and adiponectin, in both groups. Additionally, apelin was negatively correlated with ox‐LDL and HDL‐cholesterol in the pregnancy group. Conclusions Although strongly correlated with adiponectin, apelin cannot be used as a marker of insulin sensitivity, but it could serve as a marker of oxidative stress in pregnancy.     

Lipoprotein (a)

The lipids are transported by lipoproteins in the blood system. Lipoprotein (a) [Lp (a)] is a unique lipoprotein of the human plasma discovered by professor Berg in 1963. Lp (a) consists of apolipoprotein (a) and LDL particles (apolipoprotein B100). The level and size of Lp (a) are highly variable and largely determined heredity. Clinical studies on animal models have shown that elevated Lp (a) levels are linked with a higher risk of atherosclerosis, even though not all of the conclusions based on the studies that have been carried are convincing. Concentration over 35 mg/dl is considered to be a risk level. Surprisingly high Lp (a) levels in old age are associated with longevity. This may be explained by the physiological role of Lp (a) in tissue reparation, wound healing and anti-cancer effect.     

Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation

Lipoprotein(a) is an independent risk factor for cardiovascular disease. Lipoprotein(a) levels were measured in 196 patients (103 Male [M]: 93 Female [F]) with chronic renal diseases and in 116 controls. Median levels of Lipoprotein(a) [Lp(a)] were found to be significantly elevated in patients with untreated chronic renal disease (285, 285 mg/L; M, F; range 30–1675 mg/L) and in those treated with continuous ambulatory peritoneal dialysis (320, 603; M, F; range 50–1450) compared with controls (70, 51; M, F; range 1–750; p <0.01 Males, p <0.001 Females). Lp(a) levels in patients treated by haemodialysis (133, 35; M, F; range 5–685) and renal transplantation (100, 95; MJF; range 10–1700) were not significantly different from controls. Lipoprotein(a) levels correlated inversely with serum albumin in the combined dialysis group (r= -034, p < 0.001), and with urinary protein loss in the combined transplant and chronic renal diseases groups (r = 0.29, p <0.01). This correlation of Lp(a) with protein metabolism suggests a similarity with changes in other apolipoprotein-B containing lipoproteins in nephrosis. These findings may be relevant to the increased risk of atherosclerosis in patients with chronic renal disease and to their optimum mode of renal replacement therapy. (Aust NZ J Med 1992; 22:243–248.)