Objective: To investigate the efficacy of sinivastatin and aspirin as well as blood pressure controlling therapy for carotid atherosclerosis in patients with hypertension. Methods: 162 patients with essential hypertension and carotid atherosclerosis were randomized into two groups. 82 cases In the treatment group, were treated with simvastatin and aspirin as well as antihypertensive drugs; while 80 cases in the control group were treated with antihypertensive drugs alone. Intima-media thickness (IMT) of carotid arterial, carotid plaques score, blood pressure and the serum lipids were measured before and once a year after treatment for 3 years. Results: Mean IMT of carotid artery and carotid plaques score were (1.01 ± 0.12) mm and 3.8 ± 2.5 respectively in the treatment group 1 year a fter treatment, showed no difference from that before treatment. But they were (0.80 ± 0.16) mm, 2.6 ± 1.6 and (0.80 ± 0.20) mm, 2.5 ± 1.2 after 2 and 3 years respectively, which were reduced significantly compared with that of before treatment. The IMT and internal diameter ratio was also reduced significantly after treatment. Overall incidence of cardio-and cerebro-vascular events in the treatment group were 10.90% and 4.87% during the 3 years follow-up period, which were significantly lowered compared to the control group. Conclusion: Long-term simvastatin and aspirin therapy could effectively delay and reverse the progression of carotid arteriosclerosis in patients with hypertension and prevent cardio-and cerebro-vascular events when combined with antihypertensive drugs.

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AIMS:

Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-α), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti TNF-α treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease.

METHODS:

We performed a systematic review of studies examining effects of monoclonal antibodies against TNF-α on sub-clinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flow mediated dilation or forearm blood flow responses to endothelium-dependent agonists, and common carotid intima-media thickness).

RESULTS:

We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti TNF-α biologics on these measures were assessed in patients receiving anti TNF therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these only 6 were randomised clinical controlled trials (RCT). Whilst many observational studies and non-controlled studies reported positive findings, positive finding were reported in only one of six RCTs.

CONCLUSIONS:

There is no strong evidence for an effect of anti TNF-α biologics on the sub-clinical measures of arteriosclerosis or atherosclerosis examined in this review. This does not exclude a positive effect of TNF-α biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.

There remains no treatment for chronic allograft rejection mainly manifested by progressive arteriosclerosis. We investigated the effect of Allotrap peptide RDP58 therapy on arteriosclerosis in an aortic allotransplant model. RDP58 was administered intraperitoneally at 0.1, 0.5, or 2.5 mg/kg, every other day after transplantation. RDP58 therapy markedly inhibited vascular intimal thickening, media necrosis, and adventitial cellular inflammation. The attenuation of arteriosclerosis was associated with the induction of heme oxygenase (HO)-1 expression, inhibition of TNF-alpha production in aortic allografts, as well as decreased specific complement-dependent cytotoxic antibodies in serum. RDP58 inhibited both smooth muscle cell (SMC) proliferation with an 80% inhibition at 100 microM without evidence of cytotoxicity and TNF-induced apoptosis of SMCs in a dose-dependent fashion. These data suggest that the suppressive effect of RDP58 on allograft arteriosclerosis is due to multiple actions of the peptide, including induction of HO-1, inhibition of TNF-alpha, and a direct effect on SMC proliferation.

The effect of beraprost sodium, a stable prostaglandin I2 analog, on plasma lipids and apolipoproteins was examined in 18 patients with arteriosclerosis obliterans (Fontaine I) accompanied by hyperlipidemia, Twelve weeks of therapy with beraprost sodium at 120 μg daily significantly decreased plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels without a deleterious effect on plasma triglyceride, high-density lipoprotein (HDL) cholesterol, or apolipoprotein levels, A positive correlation was observed between the change in plasma total cholesterol and that in plasma LDL cholesterol due to the administration of beraprost sodium, Although this is a preliminary study, the results suggest beraprost sodium exerts an antiatherogenic effect, By lowering plasma total cholesterol and LDL cholesterol levels, beraprost sodium may prove to be important in the control of arteriosclerosis obliterans with hyperlipidemia.

In order to further investigate the radical scavenging and anti-arteriosclerotic activities of vitamin K2 and estradiol, the comparative effects of vitamin K2 and estradiol on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis with diabetes mellitus was induced by vitamin D2 and radical producing substance, streptozotocin (STZ). Pharmacological dose of vitamin K2 (100 mg/kg b.w.) and medical dose of estradiol (83 micrograms/kg b.w.) suppressed the increased serum glucose, and vitamin K2 and estradiol increased the decrease in serum insulin. Moreover, vitamin K2 and estradiol inhibited the increase of Ca and P in the aorta and the elastin fr. Vitamin K2 and estradiol decreased the increase in serum lipid peroxide (LPO). It is suggested that both the pharmacological dose of vitamin K2 and medical dose of estradiol suppressed the development of arteriosclerosis associated with diabetes mellitus, owing to radical scavenging activity of vitamin K2 and estradiol.

The relationship between the presence of arterial calcinosis and the antihypertensive response to calcium blockers was studied in 40 hypertensive patients with end-stage renal failure (ESRF) on chronic hemodialysis, before and during 16 weeks after administration of nitrendipine in monotherapy. In a double-blind, placebo-controlled, randomized study, nitrendipine reduced systolic blood pressure regardless of the presence or absence of arterial calcifications. The antihypertensive effect was significantly more pronounced in subjects with aortic calcium deposits in comparison with patients without clinical signs of arteriosclerosis (p less than 0.01). The diastolic blood pressure was significantly reduced only in patients with aortic calcifications, and remained unchanged in subjects with noncalcified aorta. The aortic pulse wave velocity decreased significantly in patients with aortic calcifications (p less than 0.001), but remained unaffected in patients with noncalcified vessels. Multivariate regression analysis showed that the antihypertensive action of nitrendipine was correlated to the presence of aortic calcium deposits independent of age or baseline blood pressure levels. The results of the present study indicate that an overt arteriosclerosis as demonstrated by the presence of aortic calcifications on abdominal radiographs is a good indication for the use of dihydropyridines in patients with ESRF.

The relationship between the presence of arterial calcinosis and the antihypertensive response to calcium blockers was studied in 40 hypertensive patients with end-stage renal failure (ESRF) on chronic hemodialysis, before and during 16 weeks after administration of nitrendipine in monotherapy. In a double-blind, placebo-randomized study, nitrendipine reduced systolic blood pressure regardless of the presence or absence of arterial calcifications. The antihypertensive effects were significantly more pronounced in subjects with aortic calcium deposits in comparison with patients without clinical signs of arteriosclerosis (p less than 0.01). Diastolic blood pressure was significantly reduced only in patients with aortic calcifications, and remained unchanged in subjects with noncalcified aorta. Aortic pulse wave velocity decreased significantly in patients with aortic calcifications (p less than 0.001), but remained unaffected in patients with noncalcified vessels. Multivariate regression analysis showed that antihypertensive action of nitrendipine was correlated with the presence of aortic calcium deposits independently of age or baseline blood pressure levels. The results of the present study indicate that an overt arteriosclerosis as demonstrated by the presence of aortic calcifications on abdominal radiographs is a good indication for use of dihydropiridines in patients with ESRF.

INTERVENTION:

Treat patients with Olmesartan (20mg) for 6 months, and then change it with Azilsartan (20mg) and treat them for additional 6 months. Measure biomarkers on 0, 6, and 12 months. Treat patients with Azilsartan (20mg) for 6 months, and then change it with Olmesartan (20mg) and treat them for additional 6 months. Measure biomarkers on 0, 6, and 12 months.

CONDITION:

chronic kidney disease

PRIMARY OUTCOME:

Changes in CKD biomarkers such as urinary protein, urinary L‐FABP and renal hypoxia measured by BOLD‐MRI, and CAVI as an arteriosclerosis biomarker

INCLUSION CRITERIA:

CKD stage G3b to G4, and A2 to A3 uncontrolled high blood pressure (>130/80) under treatment with antihypertensives other than ARB

To identify genetic mechanisms controlling apolipoprotein levels and other \'non-traditional\' risk factors in families ascertained through probands with premature coronary artery disease (CAD).