The iron hypothesis of atherosclerosis and its clinical impact

The iron hypothesis as an alternative explanation for the gender difference in the incidence and mortality of atherosclerosis has provoked increased debates and public health concerns. In this review we summarize the historical and recent literature on the iron hypothesis and discuss several related clinical issues and their implications. Apart from misconstruction of study populations, lack of a good method to reflect the iron contents of tissues may be the major factor for causing inconsistent results from epidemiological studies. Published data from 11 countries clearly indicate that the mortality from cardiovascular diseases is correlated with liver iron. We propose that redox-active iron in tissue is the atherogenic portion of total iron stores. Recently developed magnetic resonance imaging techniques in combination with Fe chelators may allow future studies to examine this component of body iron in lesions and the whole body. Several clinical situations characterized by increased iron stores have been proposed as 'human models' suitable for further tests of the iron hypothesis. Patients with end-stage renal disease may be the most unique cohort, having significant increases in their iron stores, low-density lipoprotein (LDL) oxidation, and cardiovascular events. Other patient groups may be well suited for specific studies of different atherogenic events. With a better understanding of iron-driven oxidative damage, well controlled and effectively designed studies on these models will finally bring us to the truth of the iron hypothesis.     

Menstrual Suppression, Iron Homeostasis, and Disease Risk

Menstrual blood loss may reduce risk of atherosclerotic cardiovascular and other diseases in premenopausal women (compared to men of comparable age and postmenopausal women) by maintaining relatively low levels of body iron as measured by the serum ferritin. The impact of menstrual suppression and cessation has not been adequately studied for the effects on ferritin levels or disease risk. Evidence for increased disease risk with rising body iron stores and effects of menstrual suppression on iron homeostasis are reviewed. We postulate that monitoring ferritin levels may guide preservation of optimal iron stores to reduce disease risk during menstrual suppression and cessation.     

Unbound iron binding capacity (UIBC) as a test for empty iron stores – results from the HUNT Study

Abstract

Background. When s-iron and s-transferrin are used to diagnose empty iron stores, the measurements are usually combined in the calculation of s-transferrin saturation. This may not be the best way to utilize the information in s-iron and s-transferrin, as s-transferrin alone has a better diagnostic accuracy than s-transferrin saturation. We suggest that unbound iron binding capacity (UIBC), which is s-total iron binding capacity (2 times s-transferrin) minus s-iron could be used for diagnosing empty iron stores. Methods. To test this hypothesis, we used ROC curve analysis to compare the diagnostic accuracy of s-iron, s-transferrin, s-transferrin saturation and s-UIBC in diagnosing empty iron stores in 3029 women of childbearing age. Empty iron stores were defined as s-ferritin less than 10 μg/L or less than 15 μg/L. Results. At both definitions of empty iron stores s-UIBC had a better diagnostic accuracy than the other tests, with area under the ROC curve of 0.80–0.87. This was also the trend in a subpopulation of 172 anemic women, where the area under the ROC curve of s-UIBC was 0.92. Conclusion. When diagnosing empty iron stores calculation of s-UIBC is a better way to utilize the information in s-iron and s-transferrin than is calculation of s-transferrin saturation.     

Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes

BACKGROUND: Hereditary haemochromatosis (HH) is a common autosomal recessive disease. Recently, HH heterozygosity has been identified as an independent risk factor for myocardial infarction and cardiovascular mortality. Iron may play an important role in atherogenesis by catalyzing peroxidation of low-density-lipoprotein (LDL), an essential step in atherogenesis. In iron overload conditions, non-transferrin-bound iron (NTBI) is found in serum, which can catalyze lipid peroxidation. We investigated whether sera of HH heterozygotes contain more NTBI than sera of normal controls. METHODS: In 27 treated HH homozygotes, 22 HH heterozygotes and 17 healthy control subjects, conventional parameters of iron status (serum iron, transferrin saturation, serum ferritin) were measured. NTBI was detected using HPLC after addition of nitrilotriacetic acid and pretreatment with cobalt. RESULTS: The conventional parameters of iron status were similar in the HH heterozygous group and the control group. NTBI was significantly higher in homozygotes compared to heterozygotes (1.79 micromol L-1 vs. 0.51 micromol L-1, 95% CI of the difference = 0.6-1.95, P < 0.001), and controls (1.79 micromol L-1 vs. - 0.3 micromol L-1, 95% CI of the difference = 1.36-2.81, P < 0.001). The difference in NTBI between the heterozygous subjects and control subjects was also significant (0.51 micromol L-1 vs. - 0. 3 micromol L-1, 95% CI of the difference = 0.05-1.57, P < 0.05). CONCLUSION: Phlebotomy treated HH homozygotes maintain a high and potentially harmful serum NTBI. HH heterozygotes have a higher serum NTBI than normal controls. The reported increased risk of cardiovascular events in heterozygous haemochromatosis may be explained by NTBI-catalyzed LDL peroxidation.     

Diabetic Foot Ulcers and Cardiac Autonomic Neuropathy

PurposeDiabetic foot ulcers (DFUs) and cardiac autonomic neuropathy (CAN) are severe complications of diabetes mellitus (DM). Both DFU and CAN are associated with increased risk of major cardiovascular events and mortality. Because of the clinical impact of both these conditions, it is important to establish what effect the presence of CAN has on DFU outcomes.MethodsThis is a narrative review of original research articles identified through an electronic search of PubMed, Scopus, and Google scholar databases until June 2021 exploring CAN in individuals with DFUs. We explored prevalence, patient outcomes (DFU healing and amputation), and mortality.FindingsEvidence suggests that the prevalence of CAN is high, ranging from 43% to 66% among those with DFUs. The presence of CAN may also increase the odds of developing DFUs. A single-center, prospective, observational study has suggested that the presence of CAN significantly reduces DFU healing time. The impact on amputation is indeterminate, with conflicting reports from studies reporting either no or increased risk. On the basis of limited evidence, CAN may be associated with increased mortality in individuals with DFUs.ImplicationsThe interplay between CAN and DFUs is poorly understood from current literature. Given the high prevalence of CAN in individuals with DFUs and the potential for suboptimal outcomes, further high-quality studies are required to determine future management approaches when both conditions coexist and to establish whether early CAN screening in individuals with diabetes at high risk of foot ulceration may ultimately improve their outlook.     

Mapping body fat distribution: A key step towards the identification of the vulnerable patient?

Abstract

Although excess body fat is a significant health hazard, estimation of body fat content with the body mass index may not adequately reflect the amount of atherogenic adipose tissue (AT), i.e. visceral and ectopic fat. As opposed to subcutaneous AT that supposedly acts as a metabolic sink buffering excess dietary energy, visceral or intra-abdominal AT depots respond to several external stimuli that trigger lipolysis and secretion of free fatty acids (FFAs). Reaching the liver, FFAs accumulate in the liver and, over time, promote a chronic condition known as non-alcoholic fatty liver disease (NAFLD). The liver of the typical NAFLD patient secretes large amounts of very-low-density lipoproteins, the lipid content of which may accumulate in additional organs (skeletal muscle, heart, and pancreas). Here, we review the evidence emerging from functional and population studies that point towards an important role of ectopic fat accumulation in the pathophysiology of type 2 diabetes and cardiovascular disease. We conclude that although patients with impaired glycemic control or type 2 diabetes are at increased cardiovascular disease (CVD) risk, estimating cardiovascular risk goes wellbeyond the assessment of glycemic control and traditional CVD risk factors, and the estimation of visceral/ectopic fat deposition via readily available imaging techniquesshould be considered.     

Comparative bioavailability of ferric polymaltose and ferrous sulphate in iron-deficient blood donors

Absolute iron deficiency is treated by correcting the causative lesion and then, traditionally, administering sufficient amounts of ferrous salt to return the haemoglobin level to normal and replenish body stores. The bioavailability of ferric compounds has been questioned and accordingly their therapeutic role remains controversial. A special problem is posed by regular blood donation, where the frequency of phlebotomy is limited by the haemoglobin level, which, in turn, requires maintenance of an adequate supply of iron from dietary sources. Since this latter situation may not always occur, it would be of practical benefit to have a form of supplementation that is effective and can be taken without side effects. These issues were prospectively examined in a consecutive series of otherwise healthy blood donors who developed absolute iron deficiency anaemia and were then randomly allocated to receive 60 mg of this metal as ferrous sulphate twice a day (Group 1: n = 51), 100 mg as chewable ferric polymaltose daily (Group 2: n = 53), or the latter product twice a day (Group 3: n = 55). Serial studies showed that 80% of patients in Groups 1 and 3 had reached normal haemoglobin levels by 12 weeks, but this figure was only 50% in Group 2. Similarly, the proportion of patients improving their percentage saturation of transferrin to within the normal range was significantly better in Groups 1 and 3 than in Group 2 (P < .01). However, body iron stores, reflected in serum ferritin level, was significantly better in Group 1 (P < .01); there was no difference in this respect between Groups 2 and 3. Toxicity was more severe in those receiving ferrous sulphate, with 20% having to discontinue participation owing to nausea and vomiting, whereas this was mild in those receiving ferric polymaltose and none withdrew from the trial for this reason. It can be concluded that the two forms of iron are equally bioavailable for hemoglobin regeneration, but at 12 weeks of study ferrous sulphate was superior in reconstituting stores, as reflected in the serum ferritin level. Since the ferric iron complex is associated with only minimal side effects, it may be useful in selected populations and, in the context of blood donors, valuable as a means of maintaining positive balance, thereby diminishing the number of donors rejected because of their having developed phlebotomy-iron deficiency anaemia. © 1993 Wiley-Liss, Inc.     

Comparative Absorption of Ferri-Haemoglobin-59Fe/Ferro-Haemoglobin-59Fe and 59Fe3+/59Fe2+ in Humans with Normal and Depleted Iron Stores*

Abstract. The intestinal ⁵⁹Fe absorption from ferri- and ferro-haemogIobin-⁵⁹Fe and ⁵⁹Fe³⁺ and ⁵⁹Fe⁺ was calculated from whole body-⁵⁹Fe-retention measurements in subjects with normal and depleted iron stores. A ferri-haemoglobin-⁵⁹Fe/ferro-haemoglobin-⁵⁹Fe absorption ratio of 1.03 ±0.11 was observed for the absorption of ferri-haemoglobin-⁵⁹Fe (8.6± 0.77%) and ferro-haemogIobin-⁵⁹Fe (8.7±0.94%) in persons with normal iron stores. Depletion of iron stores caused a slight but significant higher rise of ferri-haemoglobin-⁵⁹Fe absorption (22 ± 1.7%) than the increase of ferro-haemoglobin-⁵⁹Fe absorption (18 ±0.9%) so that the absorption ratio was 1.24±0.073.—This remarkable iron valence independence of haemoglobin iron absorption is in considerable contrast to the well-established valence dependence of inorganic iron absorption which favours ferrous iron absorption especially with rising iron doses. The ⁵⁹Fe³⁺/⁵⁹Fe²⁺ absorption ratio for a diagnostic 0.56 mg Fe dose increased from 0.43 in subjects with normal iron stores to 0.74 in persons with depleted iron stores, whereas this absorption ratio was augmented only from 0.21 to 0.28 for the therapeutic 50 mg Fe-dose.—The different influence of iron valence on iron absorption from inorganic and haemoglobin iron supports other evidence for the existence of two separate mechanisms for ferrous iron and haem iron absorption in humans.     

Comparing Cardiovascular Safety of Febuxostat and Allopurinol in the Real World: A Population-Based Cohort Study

ObjectiveTo determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use.Patients and MethodsWe conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined.ResultsA total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner.ConclusionThe use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes.     

Evaluation of iron status of Finnish blood donors using serum transferrin receptor

The maximum allowable frequency of blood donations has been set so that donations should not cause anaemia or depletion of iron stores. However, it has not been determined precisely how often blood donations result in depletion of iron stores. In the present study we have evaluated iron status in blood donors using serum ferritin and transferrin receptor (TfR) concentrations. The elevation of serum TfR has been reported to be the most sensitive indicator of depletion of iron stores. On the basis of ferritin values, in men who donate frequently the amount of body iron is reduced to a level very close to that found in women donating blood for the first time. When an elevation of serum TfR above 4.0 mg L-1 was used as a stringent definition of complete iron depletion, it was estimated that 17% of frequently donating women had completely lost their iron stores, while the corresponding value for men was 8%. The fact that a considerable proportion of the female blood frequent donors have completely depleted their iron stores raises the question whether the iron status of female frequent blood donors should be routinely monitored using serum transferrin receptor measurements.     

Poor iron store recovery in voluntary blood donors in the northern zone of Ghana; a five-month three-centre cohort study

ObjectiveIn Ghana, although iron deficiency is endemic, post blood donation iron supplementation is not routine. We sought to determine whether at five months post-donation of a single unit of whole blood, donors were able to recover iron stores.Materials and methodsThis three-centre cohort study recruited 164 blood donors at the Lawra, Nandom, and Bimbila communities in the northern zone of Ghana. Venous blood samples were drawn at baseline to estimate full blood count (FBC), haemoglobin variants, qualitative G6PD status, and serum ferritin. Five months post-donation, venous blood samples were drawn for a repeat measurement of FBC and serum ferritin. Data were analysed using SPSS and GraphPad prism to assess recovery of iron stores.ResultsWhereas 26.8 % had inherited haemoglobin variants, 18.9 % of the donors had qualitative G6PD deficiency. Overall, mean difference between pre-donation and five months post donation iron stores significantly differed from zero (p < 0.001; one sample t-test). After five months post donation, 76.8 % of the blood donors could not achieve pre-donation iron stores. Whereas 6.1 % and 8.5 % blood donors had depleted iron stores and iron deficient erythropoiesis at baseline, these increased to 9.8 % and 21.3 % respectively at five-month post donation. Moreover, at five months post donation, 11 % of these blood donors would have been disqualified per haemoglobin screening cut off of 12.5 g/dl.ConclusionReliance on food intake to replenish iron store lost per blood donation may not adequately assure donor health in the study area; iron supplementation should be considered.     

Improving risk stratification for cardiovascular disease

Evaluation of: Heslop CL, Frohlich JJ, Hill JS. Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography. J. Am. Coll. Cardiol. 55(11), 1102–1109 (2010).

Identifying people at high risk of cardiovascular events is the cornerstone of cardiovascular disease prevention and a major challenge for healthcare worldwide. Recently, both inflammatory and oxidative markers have been shown to improve cardiovascular risk prediction models in a wide range of patients. Here, we evaluate a recent publication investigating the value of inflammatory and oxidative markers for the prediction of cardiovascular mortality in patients with stable coronary artery disease. This study shows that the use of multiple markers may increase the predictive power of traditional risk models. The findings are discussed in the context of cardiovascular risk prediction in general.     

Why, when and how should hypertriglyceridemia be treated in the high-risk cardiovascular patient?

Recent epidemiology attests that hypertriglyceridemia may be a causal risk factor for cardiovascular disease (CVD). The specific atherogenicity of hypertriglyceridemia relates to the accumulation in plasma of triglyceride-rich lipoprotein remnants. Hypertriglyceridemia also drives a 'global' atherogenic dyslipidemic profile, which is frequent in high-risk cardiovascular patients, such as Type 2 diabetics. Elevated triglyceride in fasting or nonfasting blood samples should be a trigger for assessing atherogenic components of the lipid profile, particularly HDL-cholesterol, non-HDL-cholesterol and apoB. Residual risk of CVD remains high in statin-treated diabetic patients owing to persistent atherogenic dyslipidemia, which is not fully corrected by these agents nor by the addition of ezetimibe. Hypertriglyceridemia may then be targeted with niacin, fibrates or n-3 fatty acids, after correcting aggravating factors, especially obesity and hyperglycemia. Fibrates consistently decrease coronary events in dyslipidemic patients in outcome studies. New evidence supports adding fenofibrate to a statin in Type 2 diabetics with residual hypertriglyceridemia and low HDL-cholesterol; extrapolating from a recent meta-analysis, a 15% reduction in triglycerides could translate into a further 15% reduction in coronary events. Ongoing clinical trials may provide new evidence for adding niacin to a statin. The value of higher doses of n-3 fatty acids in reducing CVD risk remains to be demonstrated. The high triglyceride/low HDL nexus is an under-recognized risk factor for CVD that merits more detailed clinical assessment and treatment, particularly in patients with Type 2 diabetes already receiving a statin.     

Apolipoprotein C‐III predicts cardiovascular mortality in severe coronary artery disease and is associated with an enhanced plasma thrombin generation

Summary. Background: Apolipopoprotein C‐III (apo C‐III) plays a pivotal role in controlling plasma triglyceride (TG) and contributes to the atherogenic properties of TG‐rich lipoproteins. Objectives: (i) To examine the predictive value of serum apo C‐III for cardiovascular mortality in the setting of secondary prevention of coronary artery disease (CAD); and (ii) to evaluate possible associations between apolipoprotein levels and the thrombin generation assay, a global test to estimate plasma thrombogenic potential. Methods and results: A cohort of 633 patients with angiographically proven CAD was prospectively followed for a median follow‐up of 57 months. The large majority of them (92%) underwent coronary (endovascular or surgical) revascularization. During the follow‐up, 91 (14.3%) out of 633 patients died, with 64 events (10.1%) attributed to cardiovascular causes. After adjustment for all the other predictors of mortality during univariate analysis (i.e. age, statin therapy, myocardial infarction history, diabetes, hs‐CRP and creatinine), elevated apo C‐III levels (≥ 10.5 mg dL^?1– the median value) significantly predicted both total and cardiovascular mortality (HR for total mortality 2.22 with 95% CI 1.16–4.24; HR for cardiovascular mortality 2.35 with 95% CI 1.19–4.62). In a subgroup of 225 subjects, apo C‐III levels were significantly associated with endogenous thrombin potential in regression models (standardized β coefficient = 0.207, P = 0.002). Conclusions: Basal concentrations of apo C‐III levels ≥ 10.5 mg dL^?1 in CAD patients independently predicted cardiovascular mortality during the subsequent 5‐year period. Such concentrations were associated with an enhanced plasma endogenous thrombin generation, suggesting a complex interplay between TG‐rich particles and the coagulation cascade as well as a new ‘thrombogenetic’ role for apo C‐III.     

d-dimer predicts major bleeding,cardiovascular events and all-cause mortality during warfarin treatment

ObjectivesPrevious studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of d-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.Design and methodsIn a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for d-dimer, tPA, and tPA/PAI-1 complex.ResultsIn multivariate Cox regression analysis, high levels of d-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01–1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05–1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06–1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.ConclusionWe conclude that high levels of d-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.     

Endostatin predicts mortality in patients with acute dyspnea – A cohort study of patients seeking care in emergency departments

BackgroundIncreased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported.AimOur main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea.DesignCirculating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System–Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age.ResultsEach one standard deviation increment of endostatin was associated with a HR of 2.12 (95% CI 1.31–3.44 p < 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p < 0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin.ConclusionsIn an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3%.     

The GALAXY Program: an update on studies investigating efficacy and tolerability of rosuvastatin for reducing cardiovascular risk

The GALAXY Program is a series of clinical studies investigating the efficacy and tolerability of rosuvastatin in line with the hypothesis that the statin with the greatest efficacy for improving the atherogenic lipid profile and beneficially modifying inflammatory markers will also slow progression of atherosclerosis and improve cardiovascular outcomes. Completed studies report that rosuvastatin is more effective than comparator statins in reducing low-density lipoprotein cholesterol, improving the lipid profile and enabling patients to achieve lipid goals, including revised, more stringent goals, even in high-risk patients. Studies have also reported that rosuvastatin can arrest and even regress atherosclerosis. Ongoing outcomes studies will determine whether these beneficial effects of rosuvastatin translate into reduced morbidity and mortality.     

Role of stored iron in atherosclerosis

Myocardial infarction remains the No. 1 killer of American men and women, with a death rate of 225,000 per year, and stroke, the third leading cause of death in the United States, afflicts about 600,000 per year. The combined financial burden of these diseases is approximately $134 billion per year. Therefore, interventions that reduce mortality and suffering will have a significant impact on the health care system. This article summarizes research conducted during the last 2 decades that addresses the idea that stored iron plays a role in the pathogenesis of atherosclerosis and that iron reduction through phlebotomy may play a role in the treatment or prevention of atherosclerosis. Body iron stores rise after adolescence in men and menopause in women. This rise has been linked to the pathogenesis of atherosclerosis through iron-induced oxidation of low-density lipids and foam cell formation. However, the available evidence on the iron hypothesis remains circumstantial. Reduction of body iron stores in the setting of a controlled, prospective intervention trial is necessary to determine whether the amount of stored iron is related to clinically meaningful vascular disease. Such a study is feasible because reduction in iron stores can be achieved safely and predictably without induction of iron deficiency by graded phlebotomy. The Iron and Atherosclerosis Study (FeAST), a Veteran's Administration Cooperative Study, is under way to test this concept.     

Thanatopsis

PREVIEW

Diabetic patients are at high risk for morbidity and mortality from vascular complications. Therefore, it is important to identify and modify cardiovascular risk factors early in these patients. In this article, Dr Spanheimer discusses the major risk factors as well as other atherogenic factors and presents a practical approach for achieving recommended treatment goals.