Biomedical subjects

A Gottsäter

Publications and source records attributed to A Gottsäter.

At least 19 recordsLinked to original sources

PubMed2006

Managing risk factors for atherosclerosis in critical limb ischaemia.

OBJECTIVE: To review the best medical management of critical limb ischaemia (CLI). METHODS: Published studies dealing with CLI and risk factors were searched for via PUBMED. FINDINGS AND CONCLUSIONS: Patients with critical limb ischaemia (CLI) have a one and ten year mortality of approximately 20% and 75% respectively. Risk factors for the development of peripheral atherosclerosis are the same as for coronary and cerebrovascular atherosclerosis namely diabetes mellitus, hyperlipidaemia, arterial hypertension, and smoking. As there are few studies of risk factor for peripheral arterial occlusive disease (PAOD), treatment recommendations are often based on studies in patients with coronary or cerebrovascular atherosclerosis. While waiting for specific studies, CLI patients should be treated according to current guidelines for other atherosclerotic patients.

Antihypertensive Agents↗

PubMed2006

Are there differences of inflammatory bio-markers between diabetic and non-diabetic patients with critical limb ischemia?

AIM: This observational study was undertaken in order to analyse whether any differences could be detected between diabetic and non-diabetic patients with critical limb ischemia (CLI) concerning the inflammatory response. METHODS: A total number of 259 consecutive patients with CLI were treated between October 2001 and January 2003. RESULTS: Among the 259 patients, 135 (52%) had diabetes, previously known in 123, and detected during hospitalization in 12. The diabetic patients more often showed gangrene (P<0.05) and infra-inguinal atherosclerosis (84% vs 67%, P=0.001). The patients with diabetes showed a better lipid profile (total cholesterol 4.6 vs 5 mmol/L, P=0.006 and lower LDL-cholesterol (2.7 vs 3.1 mmol/L, P=0.010) despite the same frequency of statin treatment. They showed a higher creatinine (149 vs 117 micromol/L, P=0.0003) than the non-diabetic patients. Of the inflammatory markers, C-reactive protein (CRP) was equally elevated in both groups. Tumor necrosis factor-a (TNF-a) was increased among the diabetic patients (2.6 vs 1.8 pg/mL, P<0.05), and this difference was most evident in those with gangrene. Neopterin was also higher among the diabetic patients (31 vs 21 mmol/L, P<0.01), but CD40L was not different between groups. CONCLUSIONS: Diabetes mellitus was very common in CLI patients, and more often combined with renal impairment and infra-inguinal atherosclerosis. The inflammatory markers TNF-a and neopterin were elevated in patients with diabetes as compared to non-diabetic patients, but this difference cannot explain why CLI is 10 times more frequent in diabetic patients.

Aged↗

PubMed2005

Factors associated with development of large abdominal aortic aneurysm in middle-aged men.

OBJECTIVES: To investigate whether any variables in a health-screened population study were associated with later development of large abdominal aortic aneurysms (AAA). SETTING: Malmö, Southern Sweden. MATERIAL AND METHODS: Within the Malmö Preventive Study 22,444 men and 10,982 women were investigated between 1974 and 1991. The mean age at the health screening was 43.7 years. RESULTS: After a median follow-up of 21 years, 126 men and six women (p<0.001) had large AAA that were symptomatic or evaluated for operation (5 cm diameter or more) or had autopsy-verified ruptured AAA. The male group (mean age 47 years) was, because of difference in age (p<0.001) also compared with an age-matched control group. The male patients with AAA showed increased diastolic blood pressure (p<0.007) at the health screening. Smoking predicted the development of AAA (p<0.0001). No difference in forced vital capacity or BMI was seen. Those who were physically inactive (e.g. not walking or cycling to work) had an increased risk of developing AAA (p<0.001). Among the laboratory markers measured, the erythrocyte sedimentation rate did not differ (7.1+/-5.9 vs. 6.4+/-5.7), but cholesterol (6.3+/-1.12 vs. 5.8+/-1.0) (p<0.0001) and triglycerides (1.9+/-0.12 vs. 1.5+/-0.07) (p<0.001) were significantly elevated in these individuals who subsequently developing AAA. The inflammatory proteins alfa-1-antitrypsin, ceruloplasmin, orosmucoid, fibrinogen, and haptoglobulin were increased (p<0.001). CONCLUSION: Male gender, smoking, physical inactivity and cholesterol are significant factors associated with the development of AAA.

Adult↗

PubMed2005

Revascularisation of renal artery stenosis caused by fibromuscular dysplasia: effects on blood pressure during 7-year follow-up are influenced by duration of hypertension and branch artery stenosis.

Fibromuscular dysplasia (FMD) mainly affects renal arteries. Percutaneous transluminal renal angioplasty (PTRA) and surgery are effective treatments, but long-time follow-up is lacking. Retrospective follow-up for 7.0+/-4.7 years of 69 consecutive patients (age 44+/-13 years) treated for hypertension due to FMD, 59 patients underwent PTRA and eight patients surgery. In two patients no PTRA was performed. Technical success was achieved in 56 (95%) patients undergoing PTRA and all eight undergoing surgery. After successful PTRA, both systolic and diastolic blood pressures (SBP and DBP) had decreased at discharge (from 174+/-33/100+/-13 to 138+/-19/80+/-15 mmHg; P<0.0001), and remained lower at 1 month, 1 year, and last follow-up after 7.0+/-4.7 years (140+/-25/83+/-12 mmHg; P<0.0001). Serum-creatinine had decreased both at 1 year (from 84+/-28 to 75+/-13 micromol/l; P=0.0030) and last follow-up (75+/-16 micromol/l; P=0.0017). The number of antihypertensive drugs decreased (from 2.3+/-1.2 before PTRA to 1.4+/-1.3 at discharge and at 1 month; P<0.0001, and 1.6+/-1.5 at last follow-up; P=0.0011). SBP decreased more after PTRA among patients with FMD only in the main renal artery than in those with branch artery involvement (43+/-29 vs 20+/-41 mmHg; P=0.0198). Beneficial effects on BP, creatinine and antihypertensive drugs also occurred after surgery. Patients on antihypertensive drugs at last follow-up had longer hypertension duration before PTRA than those without (5.9+/-7.7 vs 1.8+/-4.1 years; P=0.0349). Cure was achieved in 16 (24%), improvement in another 26(39%), and benefit in 42(63%). In conclusion, renal artery FMD, PTRA and surgery have beneficial long-term effects, negatively affected by hypertension duration and branch artery involvement.

Adult↗

PubMed2005

Suboptimal treatment of risk factor for atherosclerosis in critical limb ischemia.

AIM: The epidemiology of critical limb ischemia (CLI) is insufficiently studied, and treatment of risk factors for atherosclerosis has received less attention in CLI patients than in patients with coronary or precerebral atherosclerosis. The aim of this study was to establish the incidence of CLI and the quality of risk factor treatment in Swedish CLI patients. METHODS: During 14 months, 316 consecutive CLI patients were referred to the Malmo Department of Vascular Diseases. Two hundred and fifty-nine (82%) consented to evaluation of intercurrent disease, medication, ankle and arm blood pressures (BP), plasma glucose and lipid levels, p-homocysteine, cardiolipin antibodies and activated protein C (APC)-resistance. RESULTS: The incidence of CLI was 38/100,000 inhabitants/year. Patient age was 75 +/- 10 years, and BP 147 +/- 26/75 +/- 14 mmHg. Systolic or diastolic BP above recommended levels (140/90 mmHg) occurred in 137 (53%) patients. P-cholesterol was 4.8+/-1.2 mMol/L, but cholesterol above recommended level (5 mMol/L) or LDL above recommended level (3 mMol/L) occurred in 125 (48%) patients. Only 24% of patients met national recommendations for both BP and lipid levels. Diabetes mellitus was previously known in 123 (47%) patients, and another 12 (5%) patients showed diabetic fasting glucose levels during the hospital stay. Eighty-four (32%) patients were active, and 72 (28%) were former smokers. Myocardial infarction or angina pectoris had previously been diagnosed in 123 (47%) patients. P-homocysteine was 17 +/- 7 _mol/l, cardiolipin antibodies occurred in 71 (27%) and APC-resistance in 34 (13%) patients. CONCLUSIONS: Patients with CLI show high comorbidity in vascular diseases and high prevalence of modifiable risk factors for atherosclerotic vascular disease. The use of evidence-based medical therapy is suboptimal in this high-risk group.

Aged↗

PubMed2004

Percutaneous transluminal renal angioplasty (PTRA) and surgical revascularisation in renovascular disease--a retrospective comparison of results, complications, and mortality.

OBJECTIVE: To evaluate results, complications and mortality following percutaneous transluminal renal angioplasty (PTRA) and open surgical revascularisation for renovascular disease. METHODS: A retrospective evaluation of 381 renovascular patients (median age 64, range 9-99 years, 152 women) treated at Malmö University Hospital during 1987-1996. Two hundred and sixty-two (69%) of the patients were treated with PTRA, 106 (28%) with open revascularisation. RESULTS: Thirty-day mortality was 2% in the PTRA group and 9% after open surgery (p<0.001). There were no differences between groups concerning the number of re-do procedures, but first re-do was performed after seven (IQR 3-14) months in the PTRA group, and after 15 (IQR 10-44) months after open revascularisation (p<0.0001). After a median follow-up of 4 months (IQR 0-13) systolic and diastolic blood pressure (BP) had decreased (p<0.0001) in both groups. The number of antihypertensive drugs was reduced (p<0.0001) and S-creatinine levels were unchanged in both groups. Long-time survival assessed with log-rank analysis was better (p<0.01) in the PTRA group. The risk ratio for death with open revascularisation was 1.69 (p<0.01). CONCLUSIONS: In this retrospective comparison, PTRA was as effective as open revascularisation, with lower complication rate and lower early and long-time mortality, but with shorter time to first re-do.

Angioplasty, Balloon↗

PubMed2004

Sustained beneficial effects on blood pressure during long time retrospective follow-up after endovascular treatment of renal artery occlusion.

We retrospectively evaluated short- and long-term effects of percutaneous transluminal renal angioplasty (PTRA) with or without stent placement of renal artery occlusion (RAO) upon blood pressure (BP), serum (s)-creatinine, and the need for antihypertensive treatment in 34 RAO patients who underwent PTRA during 1996-2002. In 24/34 (71%) treatment was considered technically successful, 22/24 (92%) were treated with PTRA + stent, two with only PTRA. Patients were followed for mean 2.6 (range 0-8) years, during which 14/34 (41%) patients died. In all 34 patients, systolic and diastolic BP (SBP and DBP) before treatment were 184 +/- 30/95 +/- 15 mmHg and had decreased at discharge (to 157 +/- 21/80 +/- 10 mmHg; P < 0.001 for both SBP and DBP), and remained lower after 1 year (154 +/- 20/83 +/- 7 mmHg; P < 0.001 for SBP and P < 0.01 for DBP), and at last follow-up (148 +/- 20/80 +/-12 mmHg; P < 0.001 for both SBP and DBP). No changes occurred in s-creatinine or the number of antihypertensive drugs. Similar results were seen in the subgroup of 24/34 (71%) patients in whom treatment was technically successful. Among the 24 patients undergoing technically successful PTRA, absence of nephrosclerosis (P = 0.035) and a shorter duration of hypertension (P = 0.020) predicted favourable clinical outcome. No adverse effects upon s-creatinine or the need for antihypertensive medication were seen in patients in whom treatment was considered a technical failure. Seven of these patients were treated with PTRA of another renal artery than the occluded, or with embolisation. In conclusion, RAO can be treated with endovascular techniques. Technically successful results with decreasing blood pressure levels were obtained in 71% of patients.

Adolescent↗

PubMed2004

Early parasympathetic neuropathy associated with elevated fasting plasma C-peptide concentrations and late parasympathetic neuropathy with hyperglycaemia and other microvascular complications.

AIMS: To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA(1c)), and future diabetic complications. METHODS: We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA(1c)), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients (age 61 +/- 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was assessed 15 years after diagnosis. RESULTS: High HbA(1c) values in the first study were associated with retinopathy (with 8.6 +/- 2.0 vs. without retinopathy 6.2 +/- 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I ratio; r(s) = -0.41; P = 0.0061) in the second study, as well as with deteriorations in GFR between the first and second study (r(s) = 0.62; P < 0.0001). Patients with parasympathetic neuropathy in the first study had significantly higher f-p-C-peptide concentrations than those without 3 years (1.20 +/- 0.43 vs. 0.86 +/- 0.40 nmol/l; P = 0.0015) and 5 years (1.20 +/- 0.44 vs. 0.82 +/- 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis. CONCLUSION: High HbA(1c) values 5 years after diagnosis of Type 2 diabetes were associated with retinopathy, disturbed parasympathetic nerve function, and deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after diagnosis was associated with high C-peptide concentrations. Parasympathetic nerve function has to be considered when beta-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes.

Autonomic Nervous System Diseases↗

PubMed2004

Plasma adiponectin and serum advanced glycated end-products increase and plasma lipid concentrations decrease with increasing duration of type 2 diabetes.

OBJECTIVE: To prospectively follow the concentrations of plasma adiponectin (p-adiponectin) and serum advanced glycation end-products (s-AGE) in relation to plasma lipids and retinopathy over 3 years in type 2 diabetic patients. DESIGN AND METHODS: P-adiponectin, s-AGE, plasma lipids and diabetic retinopathy were prospectively evaluated in 61 type 2 diabetic patients at baseline and at follow up 3 years later. RESULTS: Mean p-adiponectin (from 8.84+/-5.14 to 11.05+/-6.16 microg/ml; P=0.006) and s-AGE (from 637+/-242 to 781+/-173 ng/ml; P<0.0001) concentrations had increased at follow up. In addition, HbA1c (7.7+/-1.7 to 7.4+/-1.4%; P=0.0045) and fasting C-peptide (1.00+/-0.38 to 0.81+/-0.35 nM; P=0.019) had decreased and all lipid variables had significantly improved at follow up. P-adiponectin correlated inversely with fasting C-peptide (r(s)=-0.273; P=0.045) and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (r(s)=-0.362; P=0.011), and directly with plasma HDL cholesterol (r(s)=0.381; P=0.005) at follow up. Analysis of variance with adiponectin and s-AGE as dependent variables and fasting C-peptide, plasma HDL and plasma LDL cholesterol as covariates demonstrated that the increase in s-AGE was independent (P=0.001) and the increase in p-adiponectin dependent on covariate changes (P=0.862). There was a slight correlation between s-AGE at baseline versus the degree of retinopathy at follow up (r(s)=0.281; P=0.0499). CONCLUSION: Both p-adiponectin and s-AGE increased during the 3 years. The increase in p-adiponectin was explained by improvements in insulin sensitivity and dyslipidaemia, whereas the increase in s-AGE was independent of changes in metabolic covariates. s-AGE increase when the duration of type 2 diabetes increases.

Adiponectin↗

PubMed2003

Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors.

AIM: Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo. METHODS: TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily. RESULTS: Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001). CONCLUSION: Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Adolescent↗

PubMed2003

Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients.

AIMS: To clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. METHODS: Cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. RESULTS: Cardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 +/- 13.2% vs. 14.7 +/- 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 +/- 1.7 vs. 3.2 +/- 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). CONCLUSIONS: Cardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis.

Adult↗

PubMed2002

Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies.

OBJECTIVES: To investigate whether the interleukin-1 receptor antagonist (Il-1ra) and interleukin-1beta (Il-1beta) can be detected in human carotid artery tissue, and whether their presence is related to evidence of Chlamydia pneumoniae infection, risk factors for atherosclerosis, and clinical data. SETTING: Departments of Vascular Diseases and Surgical Pathophysiology, University Hospital, Malmö, Sweden. SUBJECTS: A total of 66 patients undergoing carotid endarterectomy (median age 74, range 53-89 years, 26 women). Il-1beta and Il-1ra were studied in carotid artery plaques and in Il-1ra in serum. RESULTS: Interleukin-1 receptor antagonist was detected in mononuclear cells in plaques from 37/66 (56%) patients. Patients with Il-1ra in plaques showed higher [2.04 (1.70-3.14) mmol x L(-1) vs. 1.69 (1.09-1.99) mmol x L(-1); P < 0.05] serum(s-)triglyceride(tg) levels, and a higher frequency of IgA seropositivity for C. pneumoniae (76% vs. 52%; P < 0.05) than those without. S-Il-1ra levels correlated with s-tg levels (r=0.38; P=0.047). There were no differences between patients with and without Il-1ra in plaques concerning s-Il-1ra, blood(b-)haemoglobin or leucocyte count, s-cholesterol, b-glucose, blood pressure, IgG seropositivity for C. pneumoniae, prevalence of neurological symptoms preceding operation, smoking, or diabetes mellitus. There were no differences in frequency of Il-1ra in plaques or in s-Il-1ra levels between patients with symptomatic and asymptomatic stenosis, between smokers and nonsmokers, or between diabetic and nondiabetic patients. Il-1beta was not detected in plaques in the current study. CONCLUSION: Interleukin-1 receptor antagonist can be detected in human atherosclerotic carotid artery plaques, and is related to s-triglyceride levels and IgA seropositivity for C. pneumoniae, but not to prevalence of neurological symptoms related to embolization.

Aged↗

PubMed2002

Platelet and leukocyte activation during aortoiliac angiography and angioplasty.

OBJECTIVE: to evaluate platelet and leukocyte activation during aortoiliac angiography and percutaneous transluminal angioplasty (PTA). METHODS: an observational study of 14 patients with aortoiliac atherosclerotic disease, nine of whom underwent PTA. The proportion of fibrinogen-, and P-selectin positive platelets, P-selectin expression on platelets, intraplatelet cGMP and cAMP, CD18 positive granulocytes, CD18 expression on granulocytes, plasma (p)-neopterin, p-TNF alpha and p- interleukin-6 were repeatedly measured in arterial blood during angiography and in venous blood before and after. RESULTS: compared to a previous venous sample, arterial intraplatelet cAMP was increased proximal to the atherosclerotic lesion before contrast infusion and PTA (median 18 [range: 14-22] vs 16 [15-21] pmol/10(9) platelets p<0.05), and intraplatelet cGMP was increased proximal to the lesion after contrast infusion and PTA (1.2 [0.8-3.9] vs 0.9 [0.6-2.5] pmol/10(9) platelets p<0.05). Four hours after angiography, both the proportion of P-selectin positive platelets (28[11-55]%) and platelet P-selectin expression (9[6-40]) had decreased (p<0.05), from arterial values distal to the lesion before contrast infusion and PTA (57 [24-78]% and 26 [10-83]). Granulocyte CD18 expression was lower during angiography than in a previous venous sample. CONCLUSIONS: the results are compatible with platelet but not leukocyte activation during peripheral angiography.

Aged↗

PubMed2002

Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia.

BACKGROUND: Hyperhomocysteinemia is a risk factor for atherosclerosis and venous thrombosis, probably exerting its effects through endothelial function. Homocysteine levels are lowered by folate supplementation, and such treatment improves endothelial function. However, whether folate supplementation decreases vascular risk and improves survival is unknown. The aim of this study was to evaluate endothelial function and mononuclear leukocyte inflammatory activity during homocysteine lowering in patients with hyperhomocysteinemia and vascular disease. METHODS: Endothelial function assessed as plasma (p-)endothelin(ET)-1 and intraplatelet cGMP and cAMP, and mononuclear leukocyte inflammatory activity, assessed as p-neopterin were studied during homocysteine lowering in 50 patients with hyperhomocysteinemia and vascular disease, randomized to folate supplementation or no treatment for 3 months. RESULTS: P-homocysteine decreased during the 3 months not only in patients on folate supplementation (from 27 [21-52] to 14 [8-41] micromol/l; p<0.001), but also in the untreated group (from 23 [20-35] to 19 [4-31] micromol/l; p<0.001). P-ET-1 decreased during folate supplementation (from 5.7 [2.7-11.6] to 4.1 [1.8-9.0] pg/ml; p<0.01), but was unchanged in the untreated group 4.1 [2.0-9.5] pg/ml and 4.5 [2.7-7.1] pg/ml). P-neopterin was unchanged in patients on folate supplementation (9.7 [5.1-54.4] and 7.6 [5.7-73.0] nmol/l), but increased in the untreated group (from 8.2 [4.7-19.5] to 8.6 [4.6-24.6] nmol/l; p<0.05). Intraplatelet cGMP decreased in patients on folate supplementation (from 0.86 [0.21-2.00] platelets to 0.56 [0.17-1.42] pmol/10(9) platelets; p<0.05), but was unchanged in the untreated group. No significant differences concerning intraplatelet cAMP occurred in either group. CONCLUSIONS: Folate supplementation in hyperhomocysteinemia is associated with decreasing levels of both ET-1 and intraplatelet cGMP, and the absence of an increase in the levels of the inflammatory mediator neopterin.

Aged↗

PubMed2002

Clinical manifestations of atherosclerosis in an elderly population are related to plasma neopterin, NGAL and endothelin-1, but not to Chlamydia pneumoniae serology.

BACKGROUND: Inflammatory mediators secreted by leukocytes are implicated in atherogenesis. Chlamydia (C.) pneumoniae infection has been suggested as a trigger of this process. We investigated relationships between C. Pneumoniae serology, inflammatory mediators and symptomatic cardiovascular disease in old age. METHODS: In a cross-sectional study at baseline with a prospective 4 year follow-up, intraplatelet cyclic 3'-5'adenosine monophosphate (cAMP) and cyclic 3'-5'guanosine monophosphate (cGMP), plasma neutrophil gelatinase associated lipocalin (NGAL), plasma soluble tumor necrosis factor receptor-1 (TNFR-1) plasma neopterin and plasma endothelin-1 (ET-1) were analysed together with IgG and IgA antibodies for C. Pneumoniae in an elderly reference population (n=140, median age 71 years, 71 females). Twenty-one subjects had clinical manifestations of cardiovascular disease at baseline and another 21 were diagnosed with cardiovascular disease during follow-up. RESULTS: In age adjusted logistic regression, subjects with cardiovascular disease showed higher plasma levels of neopterin (p=0.02), NGAL (p=0.04), and ET-1 (p<0.01). If subjects with cardiovascular disease at baseline were excluded from the analysis, higher plasma neopterin (p=0.01) and lower serum HDL cholesterol (p=0.03) predicted cardiovascular disease during follow-up. The presence of IgG or IgA against C. pneumoniae was not associated with cardiovascular disease. Neither were there any associations between inflammatory or endothelial parameters and C. pneumoniae serology. CONCLUSIONS: The inflammatory mediators neopterin and NGAL and endothelial derived vasoconstrictive ET-1 were increased in elderly subjects with symptomatic cardiovascular disease. Increased plasma neopterin predicted cardiovascular disease during follow-up. No relationships were found between C. Pneumoniae serology and cardiovascular disease.

Acute-Phase Proteins↗

PubMed2001

Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT?

The goal of this study was 3-month clinical outcome in nonanticoagulated patients with clinically suspected acute pulmonary embolism (PE) following a negative spiral CT. During a 6-month period 305 patients underwent spiral CT, of whom only 8 also had a lung scintigraphy. In patients with a final CT report read as not positive for acute PE, all hospital records and answers to a patient questionnaire were analyzed for episodes of venous thrombembolism (VTE). Acute PE was diagnosed at spiral CT in 61 patients (20%). Twenty-six of the remaining 244 patients were excluded from further analysis because of (a) long-term anticoagulation due to symptomatic acute deep venous thrombosis (n = 5), clinically diagnosed acute PE (n = 2), chronic recurrent VTE (n = 4), and cardiac disorders (n = 5); and (b) a normal perfusion scintigram (n = 4) or a negative pulmonary arteriogram (n = 6). Three patients were lost to follow-up. Among the remaining 215 patients only 10 had undergone a negative lower extremity venous study. Sixteen patients (7%) died during the follow-up period, 6 of whom underwent autopsy. Venous thrombembolism was diagnosed in three of the 215 patients (1.4%, 95% confidence limits: 0.5-4.0%), one causing the patient's death. Two patients had advanced thoracic malignancies and the third severe chronic obstructive pulmonary disease (84 years old). A negative spiral CT may be able to exclude clinically significant acute PE with the same accuracy as a normal lung scintigraphy or a negative pulmonary arteriography.

Acute Disease↗

PubMed2001

Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors.

OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING: Department of Endocrinology, University Hospital, Malmö, Sweden. SUBJECTS: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2. INTERVENTION: Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: At baseline and after 3 and 12 months. RESULTS: During 0-3 months in the HRT group, FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all decreased (P < 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P < 0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT III (P < 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P < 0.05) in total protein S after 3 and 12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total protein S (P < 0.001). CONCLUSIONS: Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.

Blood Coagulation↗

PubMed2001

High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age.

It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.

Adult↗