Vitamin D supplementation and lipid profile: What does the best available evidence show?

Vitamin D supplements have increasingly been used for the treatment and prevention of osteoporosis. Historically, effects of the vitamin on the cardiovascular (CV) system have been proposed and demonstrated in the literature, including benefits on serum lipids. Although observational studies support an association between increased serum vitamin D levels and a favorable lipid profile, interventional studies have shown no effects.     

Perfil lipídico em pacientes adultos com artrite idiopática juvenil

The inflammatory processes in the joints of a child with juvenile idiopathic arthritis (JIA) can persist into adulthood. Inflammation has been linked to distortions of the lipid profile and accelerated atherogenesis. In the present study, we examined the lipid profiles of adults with JIA compared with those of healthy people. A lipid profile of a sample of 54 adults with JIA (57.3% with polyarticular JIA, 37.0% with oligoarticular JIA, 1.9% with enthesitis-related JIA and 3.7% with systemic onset JIA) and 54 healthy subjects were compared. In the adults with JIA, data on gender, age, age at disease onset, the presence of rheumatoid factor (RF) and antinuclear antibodies (ANA), a Health Assessment Questionnaire (HAQ) and the disease duration were collected. We found that hypercholesterolaemia, increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) were more common in patients with JIA than the controls (P = 0.016, P < 0.0001 and P = 0.0008, respectively). Changes in the levels of total cholesterol (TC) and LDL were more common in the individuals who had a later onset of disease (P = 0.0017 for TC and P = 0.023 for LDL). In the entire JIA group, no other variable, such as RF, ANA, disease duration or responses to the HAQ, could be linked to dyslipidaemia (P = non-significant). We concluded that the adult patients with JIA have a lipid profile with increased TC and LDL levels and decreased levels of HDL compared to the controls. No clinical feature could be correlated with this change except for the age at disease onset.     

Effects of Three Treatment Modes on Plasma Lipids and Lipoproteins in Uraemic Patients

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.     

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.     

Effect of Pluronic L-81 on intestinal lipoprotein secretion in the rat

The hydrophobic nonionic detergent Pluronic L-81 has been shown to lower plasma very-low-and low-density lipoprotein cholesterol, thus preventing diet-induced atherogenesis. The major effect of this agent is a pronounced interference with intestinal lipid metabolism. For studying mesenteric lymph lipoproteins during detergent exposure, a combined micromorphological and biochemical assessment of mucosa and lymph during steady-state lipid absorption was performed. Pluronic L-81 was infused intraduodenally at a constant rate in combination with mixed micellar solutions or saline in mesenteric lymph fistula rats. Pluronic L-81 impairs transepithelial lipid flux during fat absorption, trapping export lipids within the enterocytes and leading to a cytosolic and endoplasmic reticulum lipid accumulation sparing the Golgi region. Pluronic L-81 markedly (P<0.001) reduces mesenteric triglyceride, phospholipid, and total cholesterol secretion almost exclusively by a reduction of chylomicron formation. Chylomicron and very-low-density lipoprotein lipid composition was only insignificantly altered, except for somewhat higher phospholipid/triglyceride ratios. The chylomicron apoprotein pattern was almost unaffected. Thus, chylomicron formation decreased dramatically without major compositional alterations. The reduction of lipid and apoprotein secretion without particle augmentation is not in favour of a selective interference of Pluronic L-81 with intestinal apoprotein B-48 secretion.Parts of this work have been presented at the Annual Meeting of the American Gastroenterological Association, Washington, DC, May 1989, and published in abstract form (1).     

Clinical significance of lipoprotein(a) in carotid plaque types and ischemic stroke in the elderly

Background:   The relationship between lipoprotein(a) (Lp(a)) and ischemic stroke is still controversial in the elderly. The purpose of the present paper was to evaluate the significance of Lp(a) in the development of extracranial carotid lesions and ischemic stroke.
Methods:   A total of 371 elderly subjects, studied with carotid ultrasonography (US) and brain computed tomography (CT), was stratified into two groups according to serum Lp(a) levels: the normal Lp(a) and high Lp(a) (>40 mg/dL) groups. Carotid plaques were divided into three types based on the US echogenicity: hypoechoic, hyperechoic, and heterogeneous plaques. Low-density areas (LDA) on brain CT images were classified into three groups depending on their distribution: basal ganglionic, cortical and only leuko-araiosis types.
Results:   The incidence of bilateral carotid lesions and the ratios of hypoechoic and heterogeneous plaques were significantly higher in the high Lp(a) group than in the normal Lp(a) group. Both the mean height and length of plaque were also greater in the high Lp(a) group. Mean Lp(a) levels were significantly elevated in cases with hypoechoic and heterogeneous types, compared to the cases without lesions. Higher mean Lp(a) levels were seen in cases with any kind of LDA than in normal subjects on CT, but there was no significant difference in the incidence of each LDA between the two groups.
Conclusions   These findings indicate that serum Lp(a) is strongly related to carotid lesions, especially hypoechoic and heterogeneous plaque types, in Japanese elderly patients. This suggests that Lp(a) could promote the formation of lipid-rich atheromatous plaque with intraplaque hemorrhage or superimposed thrombi. Serum Lp(a) also seemed to be a risk for all types of LDA.     

Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of Lp A-I in postmenopausal women

High-density lipoprotein (HDL) particles without apolipoprotein A-II (Lp A-I) may be more anti-atherogenic than HDL with apo A-II (Lp A-I/AII) and Lp A-I is reported selectively to be reduced in cases of intra-abdominal obesity. We explored the mechanisms of this reduction by studying the turnover of Lp A-I and Lp A-I/A-II in postmenopausal women well characterized for total body, regional and sub-regional adiposity by body mass index (BMI), truncal girth ratio, and abdominal magnetic resonance imaging (MRI), respectively. We tested for possible cause–effect relationships by measuring inter-correlations among these variables. Intra-abdominal fat area correlated strongly and positively with the fractional catabolic rate (FCR) of Lp A-I (r=0.98, P=0.003). Intra-abdominal fat only showed a non-significant trend toward correlation with the FCR of Lp A-I/A-II (r=0.84, P=0.07), and had no correlation with the production or transport rate (TR) of either Lp A-I or Lp A-I/A-II (r=0.48 and 0.02, respectively, P>0.1). Subjects were studied both with and without estrogen replacement, allowing exploration of a possible interaction of adiposity with estrogen effects on HDL turnover. Response of HDL turnover to estrogen did not correlate with adiposity, except for a parameter of waist to hip ratio (WHR), which predicted the increase in LP A-I TR with estrogen (r=0.84, P=0.04). We conclude that intra-abdominal fat may lower HDL levels by increasing the FCR of Lp A-I, suggesting a mechanism by which central adiposity may be proatherogenic.     

Are triglyceride-rich lipoproteins associated with aortic valve sclerosis? A preliminary report

Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS. Methods: A cross-sectional study of 246 healthy individuals (mean age 59±6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C_II and C_III levels, apo C_III levels in VLDL+LDL particles, and apo C_III ratio (C_III level in HDL/C_III level in VLDL+LDL). Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C_II, serum apo C_III and apo C_III in VLDL+LDL, and a lower apo C_III ratio. Adjusting for age and gender, a 1 S.D. increment in apo C_III in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17–2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06–2.58). Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.