A high intake of conjugated linoleic acid does not affect liver and kidney function tests in healthy human subjects.

Conjugated linoleic acid (CLA) is consumed widely as a supplement. It causes hepatomegaly in animals, but toxicological data in humans are limited. We therefore studied the effect of a high daily intake of CLA on liver and kidney function in healthy subjects. Twenty subjects received 14.6 g cis-9,trans-11 CLA and 4.7 g trans-10,cis-12 CLA isomers a day for 3 weeks. Liver and kidney function was measured at 0, 3, 7, 10, 16, and 21 days. Mean values of all tests remained within normal limits. Lactate dehydrogenase (mean+/-SD) increased from 290.9+/-43.6 to 322.5+/-60.7 U/L (p=0.04) on day 21. One subject exceeded the upper limit of normal of 450 U/L on day 21, to 472 U/L and another showed an isolated elevation to 555 U/L on day 7. Gamma-glutamyltranspeptidase increased from 12.1+/-5.9 to 13.5+/-6.2U/L (p=0.002). No one exceeded the upper limit of 50 U/L for men and 40 U/L for women. A daily intake of 19.3 g CLA for 3 weeks does not produce clinically relevant effects on markers of liver and kidney function in healthy volunteers.

[The neurovascular costoclavicular compression syndrome does not exist]. / Het neurovasculair costoclaviculair compressiesyndroom bestaat niet.

The term 'neurovascular compression syndrome' refers to a heterogeneous group of signs and symptoms thought to be generated by the compression of arteries, veins or nerves, which is caused by the anatomical relationships of muscles, ligaments and bony structures in the thoracic outlet. Most cases are related to nerve compression; arterial and venous compression accounts for 1-3% of cases. The term 'neurovascular compression syndrome', which does not refer to a single entity, is confusing and should be avoided. Rather, a clinical problem thought to arise in the thoracic outlet should be described in terms of the underlying arterial, venous or nerve impairment. Indications for surgical intervention are limited: there is no evidence to suggest that patients who undergo surgery fare better than those who receive non-surgical treatment.

Infection induced inflammation is associated with erectile dysfunction in men with diabetes.

BACKGROUND: In diabetic patients with erectile dysfunction, endothelial dysfunction is a major underlying cause. Infection-induced inflammation may be associated with endothelial dysfunction. The goal of this study was to determine whether erectile dysfunction in patients with diabetes is associated with infections of Chlamydia pneumoniae or cytomegalovirus and/or with low-grade inflammation. MATERIALS AND METHODS: Diabetic patients, 57 with and 33 without erectile dysfunction, were enrolled in a case-control study. Both groups of patients consists of type 1 and type 2 diabetics. Serum antibodies against cytomegalovirus and C. pneumoniae and markers of inflammation, including high-sensitivity C-reactive protein and fibrinogen, were measured. RESULTS: Adjusted odds ratios for erectile dysfunction in cytomegalovirus IgG, C. pneumoniae IgG and C. pneumoniae IgA seropositive men were 2.4 (95%CI; 1.0-6.0), 3.0 (95%CI; 1.2-8.1) and 1.8 (95%CI; 0.7-4.6), respectively. Odds ratios for the highest tertiles of high-sensitivity C-reactive protein and fibrinogen concentrations compared to the lowest tertile were 4.3 (95%CI; 1.4-13.1) and 6.6 (95%CI; 2.1-21.2), respectively. CONCLUSION: Elevated high-sensitivity C-reactive protein or fibrinogen serum levels and infection with cytomegalovirus or C. pneumoniae were associated with erectile dysfunction in diabetes. The relation between cytomegalovirus and erectile dysfunction is markedly present in patients with elevated high-sensitivity C-reactive protein and fibrinogen levels, suggesting a modifying effect by the inflammation.

[The metabolic syndrome: a cluster of vascular risk factors]. / Het metabool syndroom: een cluster van vasculaire risicofactoren.

The metabolic syndrome is a cluster of several vascular risk factors (impaired glucose metabolism, dyslipidaemia, hypertension and central adiposity). The prevalence of the metabolic syndrome is high, varying between 10 and 40% depending on age and sex. This prevalence will increase in the years to come due to the increased prevalence of overweight/obesity. To identify the metabolic syndrome, there is a readily applicable definition for daily clinical practice, i.e. the presence of three or more of the following characteristics: hyperglycaemia, hypertension, low plasma HDL cholesterol level, high plasma triglyceride level and central adiposity. The underlying pathophysiology is not fully clarified, but insulin resistance plays an important role in this syndrome. The metabolic syndrome is associated with increased cardiovascular morbidity and mortality and an increased risk for the development of diabetes mellitus type 2. In subjects with one or two components of the metabolic syndrome and in patients with manifest vascular disease, it seems advisable to be alert to the presence of the other components in order to either diagnose or exclude the metabolic syndrome. Although clinical evidence is lacking, from a pathophysiological point of view it seems reasonable to focus the treatment on reducing insulin resistance, which can be achieved by weight reduction and an increase in physical activity. Treatment of the individual risk factors may also be considered, depending on the degree of vascular risk.

[The diagnosis of pulmonary embolism: the best strategies according to the results of a large Dutch multicentre study]. / Diagnostiek bij longembolie; de beste strategieën volgens de resultaten van een grote Nederlandse multicenterstudie.

The Dutch national guidelines for the diagnosis of patients with clinically suspected pulmonary embolism (from 1992 en 1998) are poorly followed in clinical practice, due especially to practical objections. A large multicentre trial to investigate the diagnostic accuracy of the available modalities and of recently developed techniques such as D-dimer determination, (99m)Tc-gas-scintigraphy and spiral CT scanning was started in I997. In the first phase, the diagnostic value was assessed of: spiral CT (sensitivity 69%, specificity 84%; sensitivity for segmental and larger pulmonary embolisms (PE) 86% and for subsegmental PE 21%), (99m)Tc-gas-ventilation scintigraphy (no improvement compared to conventional ventilation scintigraphy), D-dimer determination (sensitivity for segmental PE 93% and for subsegmental PE 53%, specificity 63%), clinical decision rules (in combination with D-dimer determination; sensitivity 100%, specificity 11%) and echography of the deep venous system (sensitivity 26% for segmental PE and 7% for subsegmental PE, specificity 97%). In the second phase, the feasibility of two new potentially cost-effective diagnostic algorithms was evaluated on the basis of the results obtained in the first phase and data in the literature. In 631 patients, a clinical risk estimate was made and D-dimer determination was done, followed by a ventilation-perfusion scan and serial compression echography of the leg veins. An apparent recurrence of PE occurred in 6 of 466 patients in whom no PE had been found originally (1.3%; 95% CI: 0.5-2.8). The average costs were 812 Euro,--per patient. In 510 patients, a spiral CT followed by compression echography was performed. Recurrent PE occurred in 3 of 378 patients with initial normal tests (0.8%; 95% CI: 0.2-2.3). The average costs were 883 Euro,--per patient. A combination of both strategies can be cost-effective with a cost 674 Euro,--per patient (recurrence rate: 1.9%). Both the strategy starting with a clinical-risk estimate and a D-dimer determination as well as the strategy consisting of spiral CT and serial echography were safe and cost-effective. According to the results of a survey of hospital directors, internists and pulmonologists, both are well accepted in clinical practice.

[Acetylsalicylic acid for the primary prevention of cardiovascular disease in diabetic patients]. / Acetylsalicylzuur bij patiëten met diabetes voor de primaire preventie van cardiovasculaire aandoeningen.

Large-scale trials have shown that primary prevention using acetylsalicylic acid is useful in all patients with a cardiovascular risk exceeding 1.5% annually. In these patients the benefits of prevention outweigh the risks of bleeding. Almost all patients with diabetes mellitus are at high risk of developing cardiovascular disease. Additionally, most diabetics have other cardiovascular risks besides diabetes, providing further argument for prevention with acetylsalicylic acid. Only very few prospective trials have confirmed that acetylsalicylic acid treatment in patients with diabetes mellitus reduces their risk of cardiovascular disease and myocardial infarction. Treatment with acetylsalicylic acid should be considered in all patients with diabetes, especially in view of their decreased survival after a cardiovascular event, myocardial infarction in particular. If acetylsalicylic acid is contra-indicated treatment with clopidogrel is an alternative.

Increased arterial stiffness is independently related to cerebrovascular disease and aneurysms of the abdominal aorta: the Second Manifestations of Arterial Disease (SMART) Study.

BACKGROUND: Arterial stiffness is a risk factor for stroke and myocardial infarction. We investigated whether carotid arterial stiffness is related to other localizations of manifest arterial disease. METHODS: Carotid artery stiffness was measured by ultrasonography as the change in diameter in systole relative to the diastolic diameter in patients enrolled in the Second Manifestations of Arterial Disease (SMART) Study, a cohort study among patients with manifest cardiovascular disease or cardiovascular risk factors. The first consecutive 1561 patients with manifest cardiovascular disease were classified in 4 categories: cerebrovascular disease, coronary artery disease, peripheral artery disease, or aneurysm of the abdominal aorta (AAA). Differences in arterial stiffness among the categories were studied by linear regression analyses. Patients with coronary artery disease as single diagnosis (n=482) served as reference group. RESULTS: Patients with cerebrovascular disease (arterial distension -42.0 microm [95% CI, -57.2 to -26.8]) and those with an AAA (-64.4 microm [95% CI, -84.8 to -44.0]) had an increased carotid stiffness compared with the reference group. Adjustment for confounders attenuated the relations, which remained statistically significant (-34.2 microm [95% CI, -47.8 to -20.7] and -33.2 microm [95% CI, -51.8 to -14.6], respectively). CONCLUSIONS: Our study suggests that increased arterial stiffness is important in the pathophysiology of especially cerebrovascular disease and AAA. That the differences in arterial stiffness between disease categories attenuated after adjustment for important risk factors but remained significant suggests that besides being an element in the causal pathway, arterial stiffness is also a risk factor for cardiovascular disease itself.

[Hospital-wide vascular screening program at the University Medical Center, Utrecht: prevalence of risk factors and asymptomatic vascular disease from 1996 to 2002]. / Ziekenhuisbreed vasculair screeningsprogramma in het Universitair Medisch Centrum Utrecht: prevalentie van risicofactoren en asymptomatisch vaatlijden in 1996/'02.

OBJECTIVE: Tracing and treating cardiovascular risk factors in patients with arterial vascular disease and in patients with high risk of developing vascular diseases. DESIGN: Descriptive. METHOD: In September 1996 at the University Medical Center Utrecht, the Netherlands, a vascular screening and prevention programme was started for newly referred patients aged between 18 and 79 years presenting with one or more of the following: coronary artery disease, cerebrovascular disease, peripheral arterial disease, hypertension, diabetes mellitus or lipid disorders. In all patients, risk factors for developing (new) vascular diseases were assessed and non-invasive vascular diagnostics aimed at finding asymptomatic vascular disease were done. RESULTS: Between 1 September 1996 and 31 October 2002, 3075 patients took part in the screening programme. Within the various patient groups and often despite treatment, there was a high prevalence of hypertension, smoking, dyslipidaemia, hyperhomocystemia and overweight. In patients with peripheral artery disease, carotid artery stenosis > or = 50% was detected in 17% and an aneurysm of the abdominal aorta in 5%. In patients presenting with diabetes mellitus, hypertension or lipid disorders the prevalence of asymptomatic arterial disease was 1-5%. Asymptomatic vaso-dilatory disease in particular was uncommon. CONCLUSION: A hospital-wide vascular screening and prevention programme for a wide range of high-risk vascular patients was shown to be feasible and resulted in the detection of risk factors and asymptomatic arterial disease. It is a reliable starting point for actual risk intervention. More attention should be paid to treating existing risk factors.

The influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery in the Dutch BOA Study.

OBJECTIVE: Hyperhomocysteinemia has been identified as a risk factor for (cardio)vascular disease. Whether hyperhomocysteinemia contributes to graft failure after peripheral bypass surgery remains unclear. The present study evaluated the influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery. DESIGN: The present study was designed as a nested case-control study. METHOD: In this study (nested in the Dutch Bypass Oral anticoagulants or Aspirin Study), 150 patients with graft occlusion were each matched with two randomly selected controls with patent grafts (N = 299) from the same trial. Venous blood samples were drawn from cases and controls, and total plasma homocysteine (tHcy) was determined. Mean serum homocysteine levels and the presence of hyperhomocysteinemia (>95th percentile in healthy individuals) were compared between cases and controls. RESULTS: No significant differences were found between serum levels of homocysteine in patients with and without graft occlusion. The mean plasma homocysteine levels were 14.4 micromol/L and 14.9 micromol/L in the case and control groups, respectively. The resulting mean difference was -0.4 (95% confidence interval [CI], -1.8-0.9). The odds ratio of hyperhomocysteinemia was 0.81 (95% CI, 0.49-1.33). Adjustment for risk factors of graft occlusion did not change these results. CONCLUSIONS: Postoperative raised serum levels of homocysteine proved not to be a risk factor for graft occlusion after infrainguinal bypass grafting.

Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be an effective method to improve endothelial function in these patients. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks' administration of atorvastatin 10 mg and 80 mg on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease. RESULTS: Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilatation was found (P > 0.8). CONCLUSIONS: We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.

Homocysteine and the stage of atherosclerotic disease: a study in patients suffering from clinically silent and clinically manifest atherosclerotic disease.

BACKGROUND: Elevated serum levels of homocysteine are considered a risk factor for cardiovascular disease. It has been suggested that homocysteine is a late stage predictor of adverse cardiovascular events, which might explain reported controversies in literature. The objective of the present study was to study the relationship between homocysteine levels and the stage of atherosclerotic disease. METHODS: In a cross-sectional study we compared the prevalence of hyperhomocysteinemia in high risk patients without silent or clinically overt atherosclerosis (group I, n = 196) with two patient groups: patients with clinically manifest atherosclerosis in the past or asymptomatic atherosclerosis (group II, n = 364) and patients who currently suffer from a clinically relevant manifestation of ischemic cardiovascular disease (group III, n = 967). In addition, we related homocysteine levels with a cumulative index of atherosclerotic disease (SMART-score). RESULTS: Homocysteine levels (micromol L(-1)) for the different groups were 13.5 +/- 8.9 (group I), 13.7 +/- 8.2 (group II) and 14.7 +/- 7.7 (group III). After adjustment for age, body mass index, creatinine levels and current use of vitamins, no significant differences in the prevalence of hyperhomocysteinemia were observed, compared with the reference category. Linear regression analysis revealed a significant relationship between Smart score and homocysteine levels that remained after adjustment for potential confounders (Beta = 0.36 (0.14-0.59), P = 0.001). CONCLUSION: If homocysteine levels are associated with the presence and indicators of atherosclerotic plaque burden, then this relationship is apparently not affected by the stage of atherosclerotic disease.

Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes.

AIMS: To determine differences in the anatomic site of atherosclerosis in the lower extremity between patients with and patients without diabetes. DESIGN: Cross-sectional study of patients who underwent angiography of both legs because of symptoms of intermittent claudication, rest and/or night pain, ulceration or gangrene. METHODS: The angiographies of 37 patients with diabetes and 37 patients without diabetes, matched for age, sex and smoking behaviour, were evaluated using the Bollinger scoring system. RESULTS: The mean (sd) Bollinger score in the upper leg (from the abdominal aorta to and including the superficial femoral artery) was higher (P = 0.01) for patients without diabetes (35.3 (22.8)) than for patients with diabetes (23.3 (16.1)). In the lower leg (from the popliteal artery to the posterior tibial artery) patients with diabetes tended to have a higher score than patients without diabetes: 47.4 (34.2) and 37.6 (32.9), respectively (P = 0.22). CONCLUSION: This angiographic study confirms the clinical notion that lower limb atherosclerosis in diabetes is more severe in distal segments of the lower extremity, while the proximal segments remain less attenuated compared with patients without diabetes.

Is cardiovascular disease a risk factor in the development of axonal polyneuropathy?

OBJECTIVES: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). METHODS: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23 patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. RESULTS: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. CONCLUSION: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.

Primary and secondary prevention in cardiovascular disease: an old-fashioned concept?

OBJECTIVE: Is the concept of primary and secondary cardiovascular prevention an old-fashioned concept that needs to be re-defined? DESIGN: Discussion paper. RESULTS: Cardiovascular prevention means reduction of absolute risk for cardiovascular disease (CVD), irrespective of clinical stage. CONCLUSION: For the calculation of an individual probability to develop CVD all factors that contribute to the risk must be taken into account, including previous CVD events.

Coagulation and fibrinolysis in diabetes.

The accelerated development of atherothrombotic cardiovascular disease in type 2 diabetes mellitus may be enhanced by the presence of a prothrombotic state. This prothrombotic state includes a diminished fibrinolytic capacity and an increased coagulability. Impaired fibrinolytic capacity appears to be a hallmark of the metabolic syndrome of type 2 diabetes and can be a direct consequence of visceral obesity. In addition, a chronic low inflammatory state with hyperinsulinemia and dyslipidemia may further influence the hemostatic balance. The characteristic dyslipidemia of type 2 diabetes, coined the atherogenic lipoprotein profile, with raised plasma levels of fasting and postprandial triglyceride lipoproteins, atherogenic low-density lipoproteins, and low high-density lipoproteins, is involved in promoting a hypercoagulable state. Lifestyle and pharmacologic interventions that reduce cardiovascular risk in the general population and that may improve the metabolic syndrome may also reduce the prothrombotic state.

Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women.

OBJECTIVE: To compare the effects of 3 months treatment with tibolone (a single entity synthetic steroid hormone with estrogenic, progestanic and androgenic activities), or continuous combined conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA), with placebo, on endothelial function. DESIGN: A single center, randomized, double-blind, placebo-controlled study. SETTING: Research center as part of the University Medical Center Utrecht. SUBJECTS: One hundred and five healthy postmenopausal women, sampled from the general population. INTERVENTIONS: Three months treatment with tibolone or CEE+MPA or placebo. MAIN OUTCOME MEASURE: At baseline and after 3 months, endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. RESULTS: Results are presented as mean differences between treatment groups of endothelium dependent flow mediated dilatation (fmd) and endothelium independent nitroglycerine induced dilatation with 95% confidence intervals (95% CI). After treatment, there was a significant difference in mean fmd between the CEE+MPA group and the placebo group of 2.5% (95% CI: 0.3-4.6) while the tibolone group and the placebo group did not differ significantly (0.6%; 95% CI: 1.6-2.8). Nitroglycerine induced dilatation did not differ significantly between the groups. CONCLUSIONS: Hormone replacement therapy with CEE+MPA for 3 months increases endothelium dependent fmd of the brachial artery in healthy postmenopausal women. Tibolone did not alter fmd. The clinical significance of this improvement in fmd for cardiovascular disease risk needs to be established.

Variability of flow mediated dilation: consequences for clinical application.

BACKGROUND: Flow mediated vasodilatation (FMD), a non-invasive tool to assess endothelial function, has been shown to have prognostic value for the development of cardiovascular disease. Conventional B-mode ultrasonography has been criticised for its 'limited' resolution in vivo, which complicates reliable detection of the minute diameter changes during reactive hyperaemia. In the present study we evaluated the physical resolution, reproducibility and the capability to detect FMD impairment of a wall tracking system (WTS). METHODS: The resolution of WTS was compared with that of intravascular ultrasound (IVUS) in pig femoral arteries in vivo. Subsequently, intra- and interobserver variability of FMD testing with WTS was evaluated in 75 healthy volunteers. Finally, the effect of smoking as single risk factor for atherosclerosis on FMD in vivo was assessed. RESULTS: WTS and IVUS readings were not different (difference in arterial cross sectional area 1.97 mm(2), r=0.87). Intrasession coefficient of variation in baseline diameter was 1.1% (extremes 0.06--2.0%). Inter-session baseline diameter variation was 3.6 and 3.8% for each observer and 4.1% between observers. Intra-individual variability in FMD between sessions was considerable with coefficients of variation of 13.9% for FMD and 9.3% for NTG. Smokers had impaired FMD responses compared with matched non-smokers (4.7+/-2.4 vs. 9.6+/-4.4%, P<0.001), whereas NTG induced vasodilatation did not differ (13.4+/-6.2 vs. 15.4+/-5.1%; p=ns). CONCLUSION: WTS is a suitable technique for reproducibly assessing the brachial artery diameter in vivo with a accuracy comparable to that of IVUS. Using this sensitive technique the reproducibility of FMD in vivo proves to be poor mainly due to physiological factors. Whereas this seriously limits the use of FMD as follow-up parameter for individual subjects, FMD is demonstrated to be a useful research tool at group level.

Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women.

BACKGROUND: Microalbuminuria is an early predictor of cardiovascular morbidity and mortality, in both diabetic patients and hypertensive patients. Little is known about the relation of microalbuminuria to cardiovascular disease in women of the general population. METHODS AND RESULTS: We have studied the relation of urinary albumin levels to cardiovascular mortality in a cohort study of 12 239 postmenopausal women living in Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Albumin was determined in the urine of 561 cases and 557 controls. Data were analyzed by using a nested case-control design. The cardiovascular mortality rate (95% CI) for women who were in the highest quintile of urinary albumin levels was 13.2/1000 years (8.1 to 20.9) compared with 2.6/1000 years (2.3 to 3.1) in women without detectable urinary albumin. The age-adjusted rate ratio (95% CI) between these groups was 4.4 (2.6 to 7.6). CONCLUSIONS: This is the first large cohort study that confirms a predictive role of urinary albumin for the risk of future cardiovascular mortality independent of hypertension and diabetes. Our findings support the hypothesis that microalbuminuria is a reflection of vascular damage and a marker of early arterial disease in women from the general population.

Lipid-lowering therapy in diabetes mellitus.

Dyslipidemia emerges as an important modifiable risk factor for cardiovascular disease in diabetes mellitus, especially as part of the metabolic syndrome in type 2 diabetes. In type 1 diabetes mellitus, tight glucose regulation usually will correct dyslipidemia. Both total cholesterol and triglyceride levels predict cardiovascular disease in diabetes, and HDL-cholesterol may prove to be an even better predictor. In type 2 diabetes, increased triglyceride and reduced HDL-cholesterol levels are the key characteristics of dyslipidemia. Increased hepatic VLDL production and impaired catabolism of triglyceride-rich particles contribute to hypertriglyceridemia. Subsequent formation of small dense LDL particles leads to increased atherogenicity. Small dense LDL particles have a longer circulation time, are susceptible to glycoxidation, and are taken up by macrophages and the vessel wall. Post-hoc analysis of diabetic subgroups in primary and secondary prevention trials suggest that individuals with diabetes may enjoy substantial cardiovascular risk reduction from lipid-lowering therapy. Trials prospectively addressing the benefit of lipid lowering therapy in diabetes are under way. Target levels for lipid lowering therapy in diabetes at present stem from pathophysiological plausibility rather than from clinical proof. Intensive lipid-lowering with a statin in adequate dosage or a combination of a statin and a fibrate may be used to lower LDL-cholesterol levels to values < 2.6 mmol/l and triglyceride levels to < 1.7 mmol/l, a value at which few small dense LDL particles remain in circulation. Effective medication to raise HDL-cholesterol levels adequately are not yet available for clinical use. Treatment of diabetic dyslipidemia should be as simple as possible, given the polypharmacy that is often necessary for the patient with diabetes. Therefore, single treatment with a statin in adequate dosage is the first choice.