Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks.

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting an increasing percentage of general population worldwide. Patients with T2DM are frequently characterized by impaired renal function, primarily as a result of diabetic kidney injury, but also by other contributing factors, such as hypertension, atherosclerosis, and medications. Sodium-glucose cotransporter (SGLT)-2 inhibitors have emerged as a new, promising class of antidiabetic agents with actions that seem to extend beyond their hypoglycemic effect.

Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy.

PURPOSE/AIM: To employ corneal confocal microscopy to assess differences in the extent of corneal nerve fiber alterations between diabetic patients classed according to retinopathy status and nondiabetic patients. MATERIALS AND METHODS: Two hundred seventy-eight corneas of 139 patients with type 2 diabetes mellitus and 94 corneas of 47 age-matched control participants were scanned using corneal confocal microscopy. Images of the subbasal nerve plexus were collected and analyzed for nerve fiber density (NFD), nerve branch density (NBD), nerve fiber length (NFL), and nerve fiber tortuosity (NFT). Diabetic patients were categorized into three groups according to the classification of diabetic retinopathy (DR) proposed in the Early Treatment of Diabetic Retinopathy Study, based on indirect fundoscopy, fundus photography, and fluorescein angiography findings. A separate classification into four groups according to the severity of peripheral diabetic neuropathy (DN) was also used, based on the results of clinical and electrodiagnostic examinations. RESULTS: Average NFD, NBD, and NFL differed significantly according to DR status and were found to be lower, whereas NFT was found to be higher in diabetic patients than control participants. A positive correlation between diabetic corneal neuropathy and peripheral DN was also found. CONCLUSIONS: Nerve fiber alterations of the subbasal nerve plexus of diabetic corneas appear to progress in parallel with DR and peripheral DN. Corneal confocal microscopy could possibly represent a promising adjuvant technique for the early diagnosis and assessment of human DN.

High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFalpha treatment: correlation with disease activity.

OBJECTIVE: Ankylosing spondylitis (AS) may be associated with an increased risk for cardiovascular diseases (CVD). We investigated the prevalence of cardiovascular risk factors and metabolic syndrome (MetS) in men with AS and assessed any correlation with AS-related factors. METHODS: This was a cross-sectional study of 63 men with AS, median age 40 (19-69) years, and 126 age-matched controls. Patients were on anti-TNFalpha treatment because of considerable disease activity at some time during the course of the disease. MetS was assessed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. The risk for CVD event within the next 10 years was estimated using the Framingham equation. RESULTS: Patients had lower high-density lipoprotein cholesterol (HDL-C) (p<0.001), higher systolic (p=0.001) and diastolic (p<0.01) blood pressure compared with controls. The prevalence of the MetS was higher in patients compared to controls (34.9% vs. 19.0%; p<0.05). AS patients with MetS were older (p<0.01), with higher Framingham risk score (p=0.001), had longer disease duration (p<0.05) and higher BASDAI (5.1 vs. 3.7; p<0.05) than those without MetS, while both BASFI and CRP had an inverse correlation with HDL-C levels. CONCLUSIONS: Men with AS have a higher prevalence of cardiovascular risk factors and MetS compared with controls. The presence of MetS was associated with increased 10 year CVD risk in these patients. The association of AS disease activity with MetS suggests that CVD in AS patients may, at least in part, be attributed to the inflammatory burden of the disease.

Predicting coronary heart disease risk using the Framingham and PROCAM equations in dyslipidaemic patients without overt vascular disease.

AIM: To compare the Framingham and Prospective Cardiovascular Munster (PROCAM) risk calculations. METHODS: We calculated the risk in 234 dyslipidaemic patients without overt vascular disease and in different subgroups. For example, the proportion of patients with coronary heart disease (CHD) risk >or= 20%, the effect of including the family history (FaHist) and of adjusting raised triglyceride (TG) levels. RESULTS: The Framingham risk was significantly (p < 0.0001) higher than the PROCAM risk (with and without including the FaHist) in different subgroups and when the TGs were adjusted to 1.7 mmol/l. The percentage of patients with CHD risk >or= 20% calculated by the Framingham (based on systolic or diastolic blood pressure) and PROCAM equations was 21.4% or 23.1% and 16.2% respectively. In the tertile with the highest PROCAM risk, the Framingham score was significantly greater than the PROCAM risk only when the FaHist was included in the Framingham calculation. When we analysed risk by gender, the Framingham score did not differ but the PROCAM risk was significantly (p < 0.0001) greater in men. When TG values were adjusted to 1.7 mmol/l, the predicted risk using PROCAM changed by 0% to -2% in all subgroups. CONCLUSIONS: In dyslipidaemic patients without overt vascular disease the Framingham model predicted a higher risk than PROCAM. Thus, the Framingham equation probably leads to substantial overtreatment compared with PROCAM. However, according to the literature, even the PROCAM equation may overestimate risk. This has considerable cost implications. New more accurate risk engines are needed to calculate risk in dyslipidaemic patients without overt vascular disease.

Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins.

Atherosclerosis may be more prevalent and more extensive in individuals with rheumatoid arthritis (RA) compared with the general population. Despite the fact that traditional and novel cardiovascular disease (CVD) risk factors are clinically important in these patients, it seems that inflammation--a key feature of RA--plays a crucial role in atherogenesis. Reducing the CVD burden in patients with RA is a more complex process than in the general population, mostly due to inadequate inflammation suppression as well as multiple concomitant drug therapy. Furthermore, there is no current consensus on whether RA patients should be treated as individuals at high-risk for vascular events. Statins have proved their efficacy in reducing CVD events in the general population. Despite the fact that they are not specifically indicated in RA, there is evidence supporting a beneficial effect on CVD risk factors as well as disease activity and progression. The present review considers the traditional and novel as well as the RA-specific CVD risk factors. The current evidence supporting the use of statins in this patient population is also discussed.

Platelets and white blood cell subpopulations among patients with myocardial infarction and unstable angina.

Platelet (PLT)-endothelial cell and PLT-leukocyte interactions at lesion-prone sites might trigger a local inflammatory response early in the genesis of atherosclerosis and contribute to plaque destabilization leading to acute coronary syndromes (ACS). The aim of this study was to assess the PLT count, mean PLT volume (MPV), PLT mass, white blood cell (WBC; including eosinophils) and plasma interleukin (IL)-5, in patients with ACS and controls. PLT count, MPV, PLT mass, WBC and eosinophil percentage were determined in 167 consecutive patients with ACS (86 with acute myocardial infarction, AMI, and 81 unstable angina, UA) and 83 controls. Plasma IL-5 was measured in some patients and controls. Patients were considered in subgroups depending on smoking status and if they had or did not have diabetes mellitus (DM). The PLT count was lower in the UA and AMI groups although this did not always achieve significance. The MPV was significantly raised in all patient groups except in DM non-smokers with UA or AMI. All AMI patients had significantly higher WBC counts compared with controls. The percentage of eosinophils was lower in the UA and AMI groups although this did not always achieve significance. Plasma IL-5 levels were significantly increased in the UA and AMI groups. In conclusion, patients with ACS present with changes in the count of several cell types. These cells may become therapeutic targets and these changes may also act as markers of myocardial damage or prognosis.

Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study.

OBJECTIVES: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)-a major contributor to CVD-in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. METHODS: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. RESULTS: The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). CONCLUSION: A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.

Serum homocysteine concentration as a marker of nutritional status of healthy subjects in Crete, Greece.

BACKGROUND: Dietary habits are an important determinant of serum homocysteine (tHcy), which may be a marker rather than a cause of progression of the atherosclerotic process. The aim of the present study was to evaluate the nutritional status, and to determine the serum tHcy concentrations in healthy subjects who live in rural areas of Crete, and who theoretically follow a contemporary Mediterranean-style diet. METHODS: Serum tHcy, folate, vitamin B(12), creatinine, glucose, and the lipid profile, were measured in 203 (141 men and 62 women) healthy subjects, aged 33-78 years. The major risk factors for cardiovascular disease such as age, gender, cigarette smoking, obesity were recorded and dietary data were assessed using a 3-day weighed food intake record. RESULTS: Our population had high serum tHcy, low serum folate concentrations and lower than the traditional Cretan dietary folate intake [median (range): 12.0 (3.6-44.7) micromol L(-1), 7.9 (1.9-15.5) ng mL(-1) and 241 (68-1106) microg, respectively]. Dietary intake of fibre, omega-3, and mono- or/ polyunsaturated fatty acids was also low. An inverse relation was observed between serum tHcy concentrations and serum folate (r = -0.28; P < 0.01) and vitamin B(12) levels (r = -0.33; P < 0.001). CONCLUSIONS: Nowadays, the Cretan diet has changed towards a more westernized eating pattern. Given the analytic difficulties in determining the amount of folate in food and the inverse correlation between serum tHcy and folate levels, serum tHcy concentrations may be a useful marker for nutritional status, especially folate deficiency, in healthy subjects.

The control of dyslipidemia in outpatient clinics in Greece (OLYMPIC) Study.

The objective of this study was to determine the proportion of Greek patients referred to outpatient clinics for dyslipidemia who achieved the low-density lipoprotein cholesterol (LDL-C) goal defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines, using lifestyle changes, lipid-lowering drug treatment (LLDT), or both. Adult patients with dyslipidemia, who had been receiving a hypolipidemic diet and/or LLDT for at least 3 months were assessed in a multicenter study performed at 66 sites across Greece. Patients were followed up for an additional 3-month treatment period. Lipid levels were recorded at baseline and at the end of the study. The primary endpoint was the proportion of patients achieving their individual LDL-C target at the end of the study, according to their coronary heart disease (CHD) risk status or its equivalents, as defined by the NCEP-ATP III guidelines. Multivariate logistic models were used to identify determinants of undertreatment. The study included 2,660 adults (20-75 years) from 7 regions of Greece. Of the evaluable sample (n = 2,211; men 51%; mean age 62 +/-9 years) 81% were receiving LLDT (96% with statins and 3% with fibrates), 44% had a history of CHD, 61% arterial hypertension, 36% diabetes, and 26% a family history of premature CHD. Overall, 6% were at low CHD risk, 30% at medium CHD risk, and 63% at high CHD risk. At the end of the study, 26% of all patients and 30% of those receiving LLDT achieved the NCEP-specified LDL-C target levels. The percentage of patients at LDL-C goal according to CHD risk status was: low risk 67% (95% CI = 59-75), medium risk 29% (95% CI = 26-33), and high risk 20% (95% CI = 18-22). Statins proved to be more effective than fibrates (p <0.0001). Atorvastatin-treated subjects (n = 1,222, mean dose 19 mg/day) attained the LDL-C target (31% of the cases) at a higher rate than those receiving other LLDT (n = 574, 26% at target, p <0.01) or not receiving drug treatment (n = 415, 8%, p <0.001). This outcome was more evident in the high-CHD risk group (n = 1,402, 26% with atorvastatin vs 16% with other LLDT and 3% not receiving LLDT attained the LDL-C goal, ANOVA, p <0.001). The majority of dyslipidemic patients receiving LLDT, mainly those with high-CHD risk, are not achieving the NCEP LDL-C target. This is mainly explained by inadequate dose titration to ensure target goals are met. Promoting healthy lifestyle and appropriate LLDT (potent statins with sufficient dose titration) must be implemented to ensure that patients attain LDL-C treatment goals and thus benefit from the reduction in individual CHD risk.

Wild chamomile (Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositis.

Oral mucositis is a known complication of methotrexate (MTX) therapy, but a single efficacious intervention or agent for prophylaxis or management of this side effect has not yet been identified. We report a case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile mouthwashes.

The effects of antihypertensive therapy on haemostatic parameters.

There is extensive trial-based evidence showing that antihypertensive drugs reduce the risk of vascular events (e.g. stroke and myocardial infarction) as well as target organ damage (e.g. left ventricular hypertrophy and microalbuminuria). However, some of these benefits appear to be, at least partially, independent of the extent of blood pressure (BP) lowering. It is also evident that in certain clinical situations some antihypertensive drugs are more effective than others. In this review we discuss the effects of antihypertensive drugs on the endothelium, platelets, fibrinolysis and coagulation. These properties may account for the observed BP-independent actions. Antihypertensive drugs exert multiple effects on the vascular endothelium. These include effects on nitric oxide (NO) and angiotensin II-mediated actions. Many BP lowering drugs can inhibit platelet activity, although the relevance of this property is unknown, especially if patients are also taking platelet inhibitors (e.g. aspirin). Antihypertensive drugs also influence fibrinolysis and coagulation. These effects may be mediated by a variety of mechanisms, including altering insulin sensitivity. The haemostatic actions of antihypertensive drugs deserve greater recognition and further investigation.

The clinical and prognostic significance of erythrocyte sedimentation rate (ESR), serum interleukin-6 (IL-6) and acute phase protein levels in multiple myeloma.

Interleukin-6 (IL-6) and acute phase proteins are commonly increased in patients with multiple myeloma. Several of these acute phase proteins are believed to predict prognosis and influence survival. We measured interleukin-6 (IL-6), C-reactive protein (CRP), alpha-1-antitrypsin (a1AT), acid alpha-1-glycoprotein (a1AG), haptoglobin (HAP), transferrin (TRF), hemoglobin (Hb), beta-2-microglobulin (beta2M) and erythrocyte sedimentation rate (ESR) in 42 newly diagnosed multiple myeloma patients and 25 normal controls. At the time of blood collection, nine patients were at stage I of disease, 14 at stage II, and 19 at stage III according to the Durie and Salmon myeloma staging system. Mean +/- SD values of IL-6, CRP, a1AT, a1AG, HAP, beta2M, and ESR were significantly higher and Hb significantly lower than those found in the controls. Univariate analysis, using the log-rank test, showed that among the acute phase proteins, serum CRP (P < 0.002), a1AT (P < 0.008) and ESR (P < 0.008) were significantly correlated with survival. However, when a multivariate Cox proportional hazard model was performed, ESR, CRP, a1AT, a1AG and beta2M were identified as independent prognostic factors, while the others were not. We conclude that ESR, a simple and easily performed marker, was found to be an independent prognostic factor for survival in patients with multiple myeloma.

The effect of peripheral vascular disease on the serum levels of natural anti-oxidants: bilirubin and albumin.

BACKGROUND: Bilirubin and albumin may act as antioxidants. Their circulating levels are lower in those patients with ischemic heart disease (IHD) and could be further reduced by more extensive atherosclerosis, i.e. peripheral vascular disease (PVD). METHODS: Serum bilirubin and albumin were measured in 456 patients classified into 3 groups: 1) no clinically evident cardiovascular disease (CVD), 2) IHD present and 3) PVD present. Smoking status and gender (which affect bilirubin and albumin levels in healthy individuals) were considered separately. RESULTS: Bilirubin was lower in smoking men without CVD or with PVD than in non-smokers (p=0.02 and p=0.04, respectively) in the same groups. Non-smoking women without CVD had significantly (p=0.004) lower bilirubin levels than the corresponding group of men. Frequency analysis of male non-smokers revealed significantly (p=0.04) more patients with a lower bilirubin (<6.5 mmol/l) in the PVD compared with the no CVD group. Albumin levels showed the same trends. CONCLUSIONS: Prospective studies should consider smoking and gender when assessing the relevance of bilirubin and/or albumin levels in patients with vascular disease. Our findings support those of other studies that show that low serum bilirubin and albumin levels are associated with the presence of vascular disease.

Beneficial effect of moderate alcohol consumption on vascular disease: myth or reality?

Moderate ethanol consumption (1-3 drinks/day on 5-6 days/week) has a favourable effect on vascular disease-related mortality and morbidity [especially ischaemic heart disease (IHD)]. This cardioprotective effect may be due to significant effects on cardiovascular risk factors such as high density cholesterol (HDL) concentration (HDL protects from IHD) and an inhibition of platelet aggregation (increased platelet aggregability predicts coronary events). In contrast, alcoholics and problem drinkers have an excess of IHD-related, and possibly stroke-related, mortality. Excessive alcohol intake may raise the blood pressure. Prolonged alcohol abuse can also result in alcoholic heart muscle disease. Alcohol is the major cause of non-ischaemic cardiomyopathy in Western society. Although there is a widespread belief that red wine protects more than other alcoholic beverages, several studies do not support this interpretation.

Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease.

We evaluated the use of combination therapy (ciprofibrate 100 mg or bezafibrate 400 mg plus fluvastatin 40 mg) in 23 patients (n = 13 in the ciprofibrate group) with established cardiovascular disease. Both treatments achieved a significant (P< or =0.01) decrease in the total cholesterol (TC) (32 and 21%), triglycerides (TG) (53 and 46%) and low-density lipoprotein (LDL) (36 and 26%) levels and the TC/high-density lipoprotein (HDL) (42 and 31%) and LDL/HDL (46 and 35%) ratios. HDL levels were increased (19% for both treatment groups), but this rise only achieved significance (P=0.01) in the ciprofibrate group. Although the two patient groups were not strictly matched, the reduction in serum TC and LDL levels was greater with ciprofibrate (32 and 36%, respectively; P< or =0.001) than with bezafibrate (21 and 26%, respectively; P< or =0.01). There was a significant reduction in plasma fibrinogen levels (36.4 and 13.5% in the ciprofibrate and bezafibrate group, respectively). None of the patients reported myalgia or had abnormal creatine kinase activity or liver function tests. Combination therapy is worth considering in high-risk patients because of the advantages associated with this option. Combination therapy is competitively priced when compared with high doses of statins. An end-point-based trial is needed.

Effect of hypertension and its treatment on lipid, lipoprotein(a), fibrinogen, and bilirubin levels in patients referred for dyslipidemia.

We measured the serum lipid profile, together with plasma fibrinogen and serum lipoprotein(a) (Lp[a]), glucose, bilirubin, and albumin levels in 491 patients (310 men) who were referred for the management of primary dyslipidemia. All these variables have been shown to predict vascular events. The patients were not taking lipid-lowering drugs; hypertension was present in 156 (31.7%) of them. Of the hypertensive patients, 52 (33%) were not receiving any treatment to control their blood pressure. This omission was not due to a lower prevalence of established vascular disease. The treated hypertensives were divided into three groups according to their treatment: 62 were taking lipid-hostile antihypertensives (beta-blockers, thiazides), 37 were taking lipid-neutral antihypertensives (angiotensin converting enzyme inhibitors, Ca-channel blockers, angiotensin II receptor blockers, indapamide sustained release), and five were taking lipid-friendly antihypertensives (doxazosin). Lipid-hostile antihypertensive drugs were associated with a significantly higher fibrinogen concentration when compared with untreated hypertensives or those taking lipid-neutral/lipid-friendly drugs (median values: 383, 353, and 336 mg/dL, respectively; P < .01). Lipid-neutral/lipid-friendly antihypertensive drugs were associated with lower Lp(a) levels when compared with untreated hypertensives (median values: 22 and 45 mg/dL, respectively; P < .05). The serum bilirubin level was significantly lower in the untreated hypertensives when compared with normotensives or the treated hypertensives. There were no significant differences in lipids, glucose, or albumin among the groups of hypertensives or normotensives. The influence of antihypertensive drugs on additional cardiovascular risk factors should be considered when selecting medication to reduce blood pressure.

Smoking, diabetes and hyperlipidaemia.

The epidemiological evidence linking smoking with insulin resistance is considerable. This evidence is even more convincing because there is a dose response relationship between smoking and the risk of non-insulin dependent diabetes (NIDDM). Similarly, there is a time-dependent decrease in risk of NIDDM for those who quit smoking. Insulin resistance (in the form of impaired glucose tolerance, IGT) may precede the development of NIDDM. There is a biochemical basis for the smoking-IGT/NIDDM relationship. Smoking increases the risk of developing diabetic complications like nephropathy, neuropathy and retinopathy Smoking is also an independent risk factor for myocardial infarction and all-cause mortality in NIDDM. Smokers are both insulin resistant and lipid intolerant. Smoking cessation increases circulating high density lipoprotein (HDL) and reduces low density lipoprotein (LDL) levels, despite weight gain. Those providing advice or treatment to improve cardiovascular risk factors should be aware of these smoking-related harmful effects. This is especially true if IGT is underdiagnosed despite the fact that this condition increases the risk of vascular events. Explaining that smoking increases the chance of developing diabetes as well as raising 'blood fat' levels may convince more smokers to quit.

Smoking and urological disease.

It is important to realise that virtually every part of the body, including the urological system, is adversely affected by smoking. Smoking is the most important known preventable cause of urinary bladder cancer and is also associated with a risk of prostatic and renal cancer. The exact mechanism by which smoking increases the incidence of urological malignancy is not known. One possibility is that chemicals in cigarette smoke inhibit the synthesis of cytoprotective eicosanoids. Deficient local protection, against the hostile environment caused by the presence of urine, could then encourage the process of carcinogenesis. Smoking is a powerful predictor of erectile dysfunction; cessation may restore normal function. Cigarette smoke also exerts adverse effects on sperm motility and count. Although there is no convincing evidence of reduced fertility in male smokers, it is advisable for men to quit smoking should they have marginal semen quality and wish to start a family. Smoking causes substantial urological pathology; these facts can be used to convince patients with urological problems to quit smoking.

Prothrombotic and lipoprotein variables in patients attending a cardiovascular risk management clinic: response to ciprofibrate or lifestyle advice.

BACKGROUND: Lipid lowering drugs improve survival. However, intervention studies have focused on reducing serum total cholesterol and low density lipoprotein (LDL) concentrations and have not considered that levels of high density lipoprotein (HDL), triglycerides (TG), lipoprotein (a) and fibrinogen also predict risk and outcome. METHODS: A retrospective survey of patients with primary dyslipidaemia attending a cardiovascular risk management clinic (set in a university hospital) was initiated to assess the effect of ciprofibrate, a drug with the potential to modify all these variables. Patients who received ciprofibrate (n = 72) were compared with 64 patients who only received lifestyle advice. Both groups had a similar age and gender distribution. The ciprofibrate group had a higher cardiovascular risk load but both groups shared several other characteristics. Fasting serum total cholesterol, LDL, HDL, TG, lipoprotein (a), glucose and plasma fibrinogen concentrations were measured at baseline and after 2-4 months. RESULTS: Ciprofibrate significantly improved total cholesterol, LDL, HDL, TG, lipoprotein (a) and fibrinogen. In contrast, lifestyle advice only significantly (but less markedly) reduced serum total cholesterol and TG concentrations. CONCLUSIONS: In a clinical setting, ciprofibrate has a broad spectrum of action on several predictors of vascular events. Although our study is not of a double blind randomized design it reflects the conditions in clinical practice. Nevertheless, this type of survey has its limitations.