Cardiovascular Risk In Type Research Articles

Apolipoprotein B but not LDL Cholesterol Is Associated With Coronary Artery Calcification in Type 2 Diabetic Whites

OBJECTIVEEvidence favors apolipoprotein B (apoB) over LDL cholesterol as a predictor of cardiovascular events, but data are lacking on coronary artery calcification (CAC), especially in type 2 diabetes, where LDL cholesterol may underestimate atherosclerotic burden. We investigated the hypothesis that apoB is a superior marker of CAC relative to LDL cholesterol.RESEARCH DESIGN AND METHODSWe performed cross-sectional analyses of white subjects in two community-based studies: the Penn Diabetes Heart Study (N = 611 type 2 diabetic subjects, 71.4% men) and the Study of Inherited Risk of Coronary Atherosclerosis (N = 803 nondiabetic subjects, 52.8% men) using multivariate analysis of apoB and LDL cholesterol stratified by diabetes status.RESULTSIn type 2 diabetes, apoB was associated with CAC after adjusting for age, sex, and medications [Tobit regression ratio of increased CAC for 1-SD increase in apoB; 1.36 (95% CI 1.06–1.75), P = 0.016] whereas LDL cholesterol was not [1.09 (0.85–1.41)]. In nondiabetic subjects, both were associated with CAC [apoB 1.65 (1.38–1.96), P < 0.001; LDL cholesterol 1.56 (1.30–1.86), P < 0.001]. In combined analysis of diabetic and nondiabetic subjects, apoB provided value in predicting CAC scores beyond LDL cholesterol, total cholesterol, the total cholesterol/HDL cholesterol and triglyceride/HDL cholesterol ratios, and marginally beyond non-HDL cholesterol.CONCLUSIONSPlasma apoB, but not LDL cholesterol, levels were associated with CAC scores in type 2 diabetic whites. ApoB levels may be particularly useful in assessing atherosclerotic burden and cardiovascular risk in type 2 diabetes.

Clinical insights from the Fenofibrate Intervention and Event Lowering in Diabetes study: a community practice perspective

Achieving adequate control of cardiovascular risk in type 2 diabetes mellitus (DM) is crucially important; however, the atherogenic dyslipidaemia (including low high-density lipoprotein cholesterol and hypertriglyceridaemia) typically encountered in type 2 DM is often managed inadequately. Evidence from the Fenofibrate Intervention and Event Lowering in Diabetes study suggests that fenofibrate reduces the risk of long-term macrovascular and microvascular type 2 diabetic complications, especially in patients demonstrating features of the metabolic syndrome. Fenofibrate represents a useful treatment option for controlling cardiovascular risk in type 2 diabetes patients in the community setting.

Effect of pioglitazone and metformin fixed-dose combination on biomarkers of inflammation and dyslipidemia in patients with type 2 diabetes

Inflammation and dyslipidemia are recognized markers of cardiovascular risk in type 2 diabetes mellitus (T2DM). This 24-week, double-blind trial compared efficacy and safety of a fixed-dose combination of pioglitazone/metformin (PIO/MET) with respective monotherapy in T2DM patients who had stable HbA1c for 3 months on no antidiabetes medications. The primary endpoint was change from Baseline in HbA1c. Changes in hs-CRP, triglycerides, and lipid fractionations were secondary endpoints. Measurements of hs-CRP showed significant decrease from Baseline to Week 8 and Week 24/Final Visit with PIO/MET compared with MET monotherapy, and PIO monotherapy showed significant decrease compared with MET at Week 8 (Table 1).

Abstract 839: A Common Allele at the GRB14 Locus is Associated with Increased Cardiovascular Risk in Type 2 Diabetes: Evidence from a Pooled DNA GWA Study

Genetics factor have long been recognized as important modulators of the risk of coronary artery disease (CAD) in both the general and the diabetic population. Evidence from our group indicates that some of these genes may act synergistically with the diabetic milieu, resulting into an especially strong effect among diabetic individuals. To search the genome for variants having a major effect on CAD risk in type 2 diabetes (T2D), we conducted a 300K SNP genome-wide association (GWA) study using DNA pools made from 322 CAD-positive and 412 CAD-negative individuals with T2D of European origin from the Joslin Heart Study (JHS). SNPs associated with CAD were found to cluster on chromosomes 2q24, 5p14, 9p21, and 14q31. These association signals were confirmed by genotyping of individual DNA samples, with additive ORs in the 1.4–1.6 range. The signal on chromosome 9p21 corresponded to the CAD locus that had been identified in the general population in the vicinity of the CDKN2A/CDKN2B genes. Of the other three regions emerging from the GWA screen, chromosome 2q24 showed the strongest association with CAD. The most representative SNP at this location (rs631871, additive OR=1.53, 95%CI=1.24–1.88, p=7.5 × 10 −5 ) was placed in the 3′ flanking region of the Growth Factor Receptor-Bound 14 ( GRB14 ) gene, which codes for an adapter protein with inhibitory effects on insulin receptor signaling. A similar association was found between rs631871 and cardiovascular mortality in an independent group of 475 type 2 diabetic patients (mean age at baseline=57±10 y) who were recruited at the Joslin Clinic for genetic studies in 1994–1996. In this cohort, the cumulative 10-year cardiovascular mortality was 28.1% among homozygotes for the risk allele, 20.0% among heterozygotes, and 15.8% among homozygotes for the protective allele (age and sex adjusted additive HR=1.41, 95%CI 1.04–1.90, p=0.026). By contrast, the association with increased cardiovascular risk was not confirmed in this cohort for the signals on 5p14 and 14q31. These findings point to the insulin signaling inhibitor GRB14 as a possible modulator of cardiovascular risk among individuals with T2D.

Circulating Levels of Adipocyte and Epidermal Fatty Acid–Binding Proteins in Relation to Nephropathy Staging and Macrovascular Complications in Type 2 Diabetic Patients

OBJECTIVE—To investigate the relationships of serum adipocyte fatty acid–binding protein (A-FABP) and epidermal fatty acid–binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients.RESEARCH DESIGN AND METHODS—The associations of serum A-FABP and E-FABP with markers of renal function, nephropathy staging, and macrovascular complications were examined in 237 type 2 diabetic patients.RESULTS—Serum A-FABP and E-FABP correlated significantly with serum creatinine, mean albumin excretion rate, and glomerular filtration rate (all P < 0.001) and were independently associated with diabetic nephropathy staging (P = 0.001 and P < 0.05, respectively). Circulating levels of both types of FABP were increased (P < 0.01) in subjects with macrovascular complications. Serum A-FABP was independently associated with macrovascular complications (odds ratio 2.92 [95% CI 1.42–6.01]; P = 0.004).CONCLUSIONS—Serum A-FABP and E-FABP might be novel serum biomarkers for evaluating the progression of nephropathy and its cardiovascular risk in type 2 diabetic patients.

Combined task delegation, computerized decision support, and feedback improve cardiovascular risk for type 2 diabetic patients: a cluster randomized trial in primary care.

OBJECTIVE—The Diabetes Care Protocol combines task delegation (a practice nurse), computerized decision support, and feedback every 3 months. We studied the effect of the Diabetes Care Protocol on A1C and cardiovascular risk factors in type 2 diabetic patients in primary care.RESEARCH DESIGN AND METHODS—In a cluster randomized trial, mean changes in cardiovascular risk factors between the intervention and control groups after 1 year were calculated by generalized linear models.RESULTS—Throughout the Netherlands, 26 intervention practices included 1,699 patients and 29 control practices 1,692 patients. The difference in A1C change was not significant, whereas total cholesterol, LDL cholesterol, and blood pressure improved significantly more in the intervention group. The 10-year coronary heart disease risk estimate of the UK Prospective Diabetes Study improved 1.4% more in the intervention group.CONCLUSIONS—Delegation of routine diabetes care to a practice nurse combined with computerized decision support and feedback did not improve A1C but reduced cardiovascular risk in type 2 diabetes patients.

Influence of combined exercise training on indices of obesity, diabetes and cardiovascular risk in type 2 diabetes patients

Objective: To investigate the influence of combined exercise training on indices of obesity, diabetes and cardiovascular risk in type 2 diabetes patients. Design: A double-blind randomized controlled trial with patients receiving either combination (COM), endurance (END) or no training (C). Setting: Sint-Jozef hospital (Belgium), general practice (Holland). Subjects: Forty-six type 2 diabetes patients (17 female, 29 male). Interventions: COM versus END and C. Patients exercised for three months, three times a week for 1 hour. Main measures: Six-minute walk test (6MW T), peak Vo2, strength in upper and lower limbs, sit-to-stand, height, weight, body mass index, fat mass, glycosylated haemoglobin (HbA1c), glycaemia, triglycerides, high-density lipoprotein (HDL), total cholesterol and quality of life (General Health Survey Short Form (SF-36)). Results: COM had significant better results on sit-to-stand (P<0.05), 6MW T (P<0.01), strength in upper (P<0.001) and lower limbs (P<0.001) compared with C. A different evolution among COM and C was found for HbA1c (P<0.05) and cholesterol (P<0.01), both decreased in COM and increased in C. HDL increased in COM and decreased in C (P<0.01). END had significant higher results on the 6MW T (P<0.01) compared with C. Compared with END, COM had significantly higher results on strength in upper (P<0.01) and lower limbs (P<0.01). The evolution of SF-36 items was not significantly different between the three groups. Conclusion: In diabetes type 2 patients, COM had significant better effects on indices of physical condition, diabetes and cardiovascular risk compared with C. Compared with END, COM gave a tendency towards better results, however more research with a larger number of participants is needed.

Pilot Program Cuts Cardiovascular Risk in Type 2

Pilot Program Cuts Cardiovascular Risk in Type 2

Haptoglobin Genotype

Haptoglobin is a plasma protein that binds free hemoglobin, thereby inhibiting hemoglobin-induced oxidative damage. We investigated the association between the haptoglobin genotype and the incidence of coronary artery disease (CAD) in a cohort of individuals with childhood-onset type 1 diabetes. Participants from the Epidemiology of Diabetes Complications Study who were free of CAD at study entry and had DNA available were selected (n = 453, mean age 27.1 years, and diabetes duration 18.8 years). CAD was defined as angina, ischemic electrocardiogram, myocardial infarction confirmed by Q-waves on electrocardiogram or hospital records, angiographic stenosis >50%, or revascularization. The proportions of the cohort with the haptoglobin 1/1, 2/1, and 2/2 genotypes were 11.5, 41.3, and 47.2%, respectively. During 18 years of follow-up, there were 135 (29.8%) incident CAD events. Univariately, the proportion of CAD events increased from 15.4 to 28.3 and 34.6% for haptoglobin 1/1, 2/1, and 2/2, respectively (P = 0.02, P-trend = 0.007). Cumulative incidence (including 33 baseline prevalent cases) also increased from 24.1 to 32.3 and 39.1%, respectively (P = 0.07, P-trend = 0.02). In Cox proportional hazards models adjusting for traditional CAD risk factors, the haptoglobin 2/2 genotype was associated with increased CAD incidence compared with the haptoglobin 1/1 genotype (hazard ratio [HR] 2.21, 95% CI 1.05-4.65, P = 0.04). Although the risk associated with the haptoglobin 2/1 genotype did not reach significance (1.78, 0.84-3.79, P = 0.13), there remained a significant trend across the three groups (P = 0.03). These data support the hypothesis that the haptoglobin genotype influences cardiovascular risk in type 1 diabetes.

Diabetic dyslipidemia and atherosclerosis: Evidence from clinical trials

Diabetes is a highly prevalent disease in the United States and is increasing in both incidence and prevalence. Atherosclerotic vascular disease is a major cause of morbidity and mortality in diabetic patients. Type 2 diabetes is characterized by insulin resistance and frequently co-exists with a variety of cardiovascular risk factors, including hypertension, obesity, dyslipidemia, and physical inactivity. Hygienic measures such as weight loss and exercise should form the basis of therapeutic interventions in the prevention and treatment of type 2 diabetes. The role of dyslipidemia as a causal factor in vascular disease associated with diabetes was previously downplayed because total cholesterol was frequently normal or minimally elevated. However, diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein, and small, dense low-density lipoprotein, the combination of which has been termed the "lipid triad." The role of lipid modification as a means to decrease cardiovascular risk in type 2 diabetes has recently been clarified by a number of clinical trials. Subgroup analysis in early studies implied the potential for benefit of lipid modification in diabetes. The results of these early studies prompted the design of large-scale intervention trials that employed statin and fibric acid derivatives in diabetes patients. The preponderance of data from the statin trials implicates significant clinical benefit in cardiovascular risk reduction. The fibric acid derivatives have theoretic advantages in diabetic dyslipidemia. However, the robust bulk of clinical data obtained from prospective statin studies is lacking for the fibric acid derivatives, and the results of the major trials are equivocal.

Review: The role of fenofibrate in reducing cardiovascular risk in type 2 diabetes

Dyslipidaemia (elevated triglycerides, low high-density lipoprotein-cholesterol [HDL-C] and an increase in small, dense low-density lipoprotein [LDL] particles) is an important contributor to the increased cardiovascular risk associated with type 2 diabetes. Lowering LDL-C levels with a statin is the main focus of lipid-modifying intervention. Fibrates are effective against all components of this atherogenic mixed dyslipidaemia. Adding a fibrate to primary statin therapy is a logical approach to achieving all lipid targets. Evidence from the Fenofibrate Invention and Event Lowering in Diabetes trial also shows that fenofibrate is a well-tolerated option with potential benefits on the progression of microvascular complications of type 2 diabetes. Thus fenofibrate-statin combination therapy may translate into greater reductions in vascular risk.fenofibrate, safety, type 2 diabetes.

Effect of pioglitazone on the drivers of cardiovascular risk in type 2 diabetes

The prevalence of type 2 diabetes and its associated mortality and morbidity are continuing to increase across the world. People with type 2 diabetes typically have a cluster of risk factors for cardiovascular disease, including hyperglycaemia, hypertension and lipid abnormalities, which contribute to the high cardiovascular morbidity and mortality in these patients. Targets for glycosylated haemoglobin, lipids and blood pressure are becoming more stringent, and most patients will require multiple therapies to maximally reduce cardiovascular risk. In a large randomised, controlled, long-term cardiovascular outcomes study pioglitazone showed durable glycaemic control, a powerful insulin-sparing effect and changes in the lipid profile associated with reduced cardiovascular risk. This article reviews these metabolic findings in the context of previous randomised, controlled studies for pioglitazone and discusses whether the integration of this agent into the treatment regimen of appropriate patient groups has the potential to improve cardiovascular outcomes in type 2 diabetes.

Diabetic dyslipidemia and atherosclerosis: Evidence from clinical trials

Diabetes is a highly prevalent disease in the United States and is increasing in both incidence and prevalence. Atherosclerotic vascular disease is a major cause of morbidity and mortality in diabetic patients. Type 2 diabetes is characterized by insulin resistance and frequently co-exists with a variety of cardiovascular risk factors, including hypertension, obesity, dyslipidemia, and physical inactivity. Hygienic measures such as weight loss and exercise should form the basis of therapeutic interventions in the prevention and treatment of type 2 diabetes. The role of dyslipidemia as a causal factor in vascular disease associated with diabetes was previously downplayed because total cholesterol was frequently normal or minimally elevated. However, diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein, and small, dense low-density lipoprotein, the combination of which has been termed the "lipid triad." The role of lipid modification as a means to decrease cardiovascular risk in type 2 diabetes has recently been clarified by a number of clinical trials. Subgroup analysis in early studies implied the potential for benefit of lipid modification in diabetes. The results of these early studies prompted the design of large-scale intervention trials in diabetes patients that employed statin and fibric acid derivatives. The preponderance of data from the statin trials implicates significant clinical benefit in cardiovascular risk reduction. The fibric acid derivatives have theoretic advantages in diabetic dyslipidemia. However, the robust bulk of clinical data obtained from prospective statin studies is lacking for the fibric acid derivatives, and the results of the major trials are equivocal.

Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies

To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).

Adiponectin gene and cardiovascular risk in type 2 diabetic patients: a review of evidences

Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its clinical complications as compared to non-diabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors like arterial hypertension, central obesity and dyslipidemia. Genetic variability affecting many areas such as lipid and energy metabolisms, hypertension and haemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall will have an impact on the development of macrovascular complications in diabetic patients. Adiponectin is abundantly secreted by adipocytes. It plays important roles in lipid and glucose metabolisms and has direct anti-inflammatory and anti-atherogenic effects. In this review, we summarize recent data from the literature suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ) in the genetic determinants of cardiovascular disease in diabetic subjects.

Non-HDL cholesterol versus Apolipoprotein B in the identification of dyslipidemic phenotypes associated with cardiovascular risk in type 2 diabetic dyslipoproteinemia

Summary Objective Few studies have compared non-HDL cholesterol (non-HDLc) and Apolipoprotein B (apoB) as markers of atherosclerotic risk. No such study has yet been undertaken in Asian-Indians who have a different lipid–lipoprotein profile than their Western counterparts. Our aim, therefore, was to evaluate the role of non-HDLc and apoB, as markers of all potentially atherogenic species, and to further assess as to which is the better index of the risk of cardiovascular disease (CVD) in type 2 diabetic subjects. Research design and methods Lipidic parameters, apoB and carotid mean intima–media thickness (IMT) were determined in the 95 diabetic subjects included in the study. Subjects were classified on the basis of apoB and triglyceride as well as non-HDLc and triglyceride levels. Agreement of the resultant phenotypes with IMT was assessed (correlation and concordance ( κ ) analysis), and the major contributor to the variance of IMT was determined using multistep linear regression. Results HyperapoB was the most prevalent lipoproteic abnormality. The correlation between apoB and non-HDLc was strong in the whole cohort ( r = 0.60, p r = 0.67, p κ = 0.490, p κ = 0.403, p κ = 0.598, p κ = 0.481, p κ = 0.387, p κ = 0.043, p = NS). Further apoB was a better predictor of IMT in all the subgroups as well as the whole cohort ( R 2 = 0.378, β -coefficient = 0.002) as compared to non-HDLc ( R 2 change = 0.030, β -coefficient = 0.0017). Conclusions Non-HDLc and apoB are equivalent atherogenic markers of cardiovascular risk in hypertriglyceridemic diabetic subjects, but apoB is a better index of the risk of cardiovascular disease in normotriglyceridemic subjects. Thus, measurement of apoB might be helpful in identification of a subgroup of apparently normolipidemic subjects who have hyperapoB and thus stand increased cardiovascular risk.

Fenofibrate therapy and cardiovascular protection in diabetes: recommendations after FIELD

The aim of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was to provide valuable information on the ability of fibrates to reduce cardiovascular risk in type 2 diabetes. The purpose of this review is to analyse results from FIELD and to see whether they may lead to modify the recommendations for treatment of diabetic dyslipidemia. In FIELD, fenofibrate therapy was associated with a nonsignificant 11% reduction in the primary endpoint (coronary heart disease death, nonfatal myocardial infarction), corresponding to a significant 24% reduction in nonfatal myocardial infarction (P = 0.010) and a nonsignificant 19% increase in CHD mortality. Fenofibrate reduced CHD events only in patients in primary prevention, but not in secondary prevention. Fenofibrate treatment was associated with less albuminuria progression and less retinopathy needing laser treatment. FIELD's results are somewhat disappointing. The relatively low cardiovascular risk population from FIELD and the 'pollution' by statin therapy may not totally explain the weak results of fenofibrate in the reduction in CHD events. The significant increase in plasma homocysteine observed with fenofibrate could partly explain not only the higher number of venous thrombotic events, but also the poor effect of fenofibrate in reducing clinical outcomes, more particularly in patients with previous cardiovascular disease.

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.

Reducing vascular risk in the diabetic patient: implications from the FIELD study

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, involving 9, 795 patients with type 2 diabetes, is the largest study to date investigating the role of a lipid-modifying therapy in reducing cardiovascular risk in type 2 diabetes. Although the reduction in the primary end point (non-fatal myocar-dial infarction [MI] and coronary heart disease [CHD] death) did not reach statistical significance, fenofibrate treatment was associated with a significant reduction in total cardiovascular events, largely driven by reductions in non-fatal MI and revascularisation procedures. Subgroup analyses demonstrated greater treatment effect in patients without prior cardiovascular disease than in those with established cardiovascular disease (relative risk reduction for CHD events of 25%, p=0.014 vs. a non-significant 8% increase, respectively; and for total cardiovascular events of 19%, p=0.004 vs. no effect). Differences in the magnitude of the reduction in cardiovascular risk between studies emphasise the importance of considering patient characteristics, such as duration of diabetes, concomitant lipid-modifying therapy, glycaemic control and prior cardiovascular disease, which may all influence treatment response. Taking these factors into account, as well as the promising effects on microangiopathy observed in FIELD, suggests that fenofibrate may have a role as a well-tolerated treatment (most likely in combination with a statin) in patients with early stage type 2 diabetes without evidence of macrovascular disease.

Importance of blood glucose management in the multifactorial approach of absolute cardiovascular risk in type 2 diabetes: the lessons from the Steno 2 Study

The problem of blood glucose as a cardiovascular risk factor has long been debated. Indeed, increasing arguments confirm the importance of blood glucose on cardiovascular risk, as shown by the results from epidemiological studies and therapeutic investigations. However, the literature has demonstrated the importance of postprandial blood glucose, or post-load-glucose, on cardiovascular risk. One could think that blood glucose, in particular postprandial blood glucose, is an independent, although not major, cardiovascular risk factor compared to other classical risk factors such as hypercholesterolemia, high blood pressure, and smoking, but it potentiates the risk when it coexists with these classical risk factors. This explains the increased prevalence of cardiovascular morbi-mortality in diabetic patients, in particular type 2 diabetes. Multifactorial treatment can reduce the cardiovascular risk by 55%, as the Steno 2 study demonstrated.