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To evaluate the treatment of type 2 diabetes from a cardiologist’s view. A new era in the treatment of type 2 diabetes began for the cardiologist in 2015 with the publication of the EMPA-REG outcome trial finding a significant reduction in CV death with empagliflozin (oral sodium-glucose co-transporter-2 [SGLT2] inhibitor) in patients with type 2 diabetes at increased cardiovascular risk. Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke). Both classes have demonstrated significant renal protection when added to usual care. Moreover, there may be some exciting new benefits of SGLT2 inhibitors for patients with heart failure. These research studies are underway. These two new classes of cardiovascular drugs for type 2 diabetes usher in a new era for the cardiologist who sees greater than 50% of patients with diabetes. The off-target effect of these agents is different as with all new cardiovascular compounds. While safety profiles in these populations are consistent with the known effects of these classes, new off-target effects have been seen with some agents in this class. Ongoing collaboration between cardiologists and other care providers remains important in the implementation of the evidence and care of patients with type 2 diabetes.

The aim of this study was to see if there is any association between masked hypertension (MHTN) and orthostatic HTN (OHTN). In addition, we evaluated if MHTN was associated with diabetes (DM). Lastly we compared BP and HR changes between DM and non-diabetics (NDM)pts. We performed ambulatory BP monitoring (ABPM) in 70 consecutive pts referred to us for evaluation of hypertension. From this number of pts there were 20 pts with OHTN for an incidence of 28%. There were 8 pts with MHTN for an incidence of 11.4%. There were 26 pts with DM and 44 pts were NDM The studies were performed after 5 minutes of rest. We obtained BP’s in the dominant arm. We subsequently performed the 24hs ABPM using Space Lab On Trak 90227 monitors. Out of 8pts with MHTN, none had OHTN and only 2 were pts with DM. In addition, we compared age, weight, BP sitting and standing as well as HR sitting and standing in our 70 patients that were divided in 2 groups, DM v/s NDM. The following table depicted our results: In summary, we found a higher sitting diastolic BP in nondiabetic pts. There was no significant difference between both groups in the remaining parameters. In conclusion, in our small population of pts there was no association between MHTN and OHTN. The association between MHTN and DM was very low. When comparing 8 different parameters depicted in the table the only significant difference between DM and NDM was on the sitting diastolic BP.

Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers activation of the sympathoadrenal system, leading to an increase in counter-regulatory hormones and, consequently, increased myocardial workload and oxygen demand. Additionally, hypoglycemia triggers proinflammatory and hematologic changes that provide the substrate for possible myocardial ischemia in the already-diseased diabetic cardiovascular system. Hypoglycemia creates electrophysiologic alterations causing P-R-interval shortening, ST-segment depression, T-wave flattening, reduction of T-wave area, and QTc-interval prolongation. Patients who experience hypoglycemia are at an increased risk of silent ischemia as well as QTc prolongation and consequent arrhythmias. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an increase in all-cause mortality with intensive glycemic control, whereas the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study and Veteran's Affairs Diabetes Trial (VADT) showed no benefit with aggressive glycemic control. Women, elderly patients, and those with renal insufficiency are more vulnerable to hypoglycemic events. In fact, hypoglycemia is the most common metabolic complication experienced by older patients with DM in the United States. The concurrent use of medications like β-blockers warrants caution in DM because they can mask warning signs of hypoglycemia. Here we aim to elucidate the pathophysiology, review the electrocardiographic changes, analyze the current clinical literature, and consider the safety considerations of hypoglycemia as it relates to the cardiovascular system. In conclusion, in the current era of DM and its vascular ramifications, hypoglycemia from a cardiologist's perspective deserves due attention.

Red blood cell distribution width (RDW) is an automated measure of red blood cell size. It is considered a novel biomarker, independently associated with morbidity and mortality in cardiovascular disease (CVD). RDW is elevated in prehypertensive and hypertensive patients; particularly in non-dippers

Diabetes mellitus (DM) is well known to be a coronary artery disease risk equivalent but the cellular mechanism is not completely understood. Recently, virtual histology intravascular ultrasound has demonstrated that patients with DM tend to have a higher occurrence of vulnerable plaques as compared with patients without DM. Insulin-sensitizing agents, such as metformin, have been shown to have limited cardioprotective effects, whereas thiazolidinediones, such as rosiglitazone, have been reported to have possible deleterious effects on cardiovascular mortality in a meta-analysis; however, limited data exist. In contrast, pioglitazone has been reported to have a significant benefit in patients with type 2 DM with acute coronary syndrome (ACS). Animal and human studies have demonstrated the myocardial protective effects of incretins and hold promise in reducing the incidence of major adverse cardiac events in patients with DM. Moreover, in addition to aspirin, the early use of potent antiplatelet agents, such as prasugrel and intravenous glycoprotein IIb-IIIa inhibitors, in patients with DM presenting with ACS is crucial for reducing cardiovascular events in most patients. Thus, patients with DM deserve special attention in global risk factor reduction and development of newer therapeutic agents to improve glycemic control while minimizing or reducing cardiovascular events. This article focuses on ACS in patients with DM, the pathophysiology of "vulnerable blood" in patients with DM, and newer treatment strategies to improve outcomes in this high-risk patient population.

Evidence-based medicine is key to the cardiologist’s role in the management of type 2 diabetes. Proven therapies that reduce cardiovascular (cV) events with few off-target effects are imperative. evidence from epidemiology studies supports the concept that increased blood sugar is correlated with increased cV events. unfortunately, the lowering of glucose with current agents shows limited benefit in reducing cV events. Metformin in the obese individual reduced cV events and is currently first-line therapy in most clinical practice guidelines. recently, a meta-analysis reported that current hypoglycemic agents did not improve cV outcomes and were possibly harmful. Possible exceptions come from the Prospective pioglitazone clinical trial in macrovascular events (Proactive), a secondary prevention trial in patients with prior myocardial infarction in which pioglitazone was found to reduce cV events. glucagon-like peptide-1 (gLP-1) agonists appear to be the most exciting new cV agents, but a dipeptidyl peptidase-4 (DPP4) inhibitor (sitagliptin) combined with a high-dose angiotensin-converting enzyme inhibitor (Acei) (enalapril) may increase blood pressure and heart rate. Lifestyle modification and proven global risk reduction are still the number one ways to reduce cV events in type 2 diabetes.

The global epidemic of diabetes mellitus (~95% type 2 diabetes) has been fueled by a parallel increase in obesity and overweight. Together, these metabolic disease epidemics have contributed to the increasing incidence and prevalence of cardiovascular disease. The accumulation of metabolic and cardiovascular risk factors in patients with type 2 diabetes--risk factors that may exacerbate one another--complicates treatment. Inadequate treatment, treatment that fails to achieve goals, increases the risk for cardiovascular morbidity and mortality. From a clinical perspective, type 2 diabetes is a cardiovascular disease, an observation that is supported by a range of epidemiologic, postmortem, and cardiovascular imaging studies. Vascular wall dysfunction, and particularly endothelial dysfunction, has been posited as a "common soil" linking dysglycemic and cardiovascular diseases. Vascular wall dysfunction promoted by environmental triggers (e.g., sedentary lifestyle) and metabolic triggers (chronic hyperglycemia, obesity) has been associated with the upregulation of reactive oxygen species and chronic inflammatory and hypercoagulable states, and as such with the pathogenesis of type 2 diabetes, atherosclerosis, and cardiovascular disease. Glucagon-like peptide-1 (GLP)-1, an incretin hormone, and synthetic GLP-1 receptor agonists represent promising new areas of research and therapeutics in the struggle not only against type 2 diabetes but also against the cardiovascular morbidity and mortality associated with type 2 diabetes. In a number of small trials in humans, as well as in preclinical and in vitro studies, both native GLP-1 and GLP-1 receptor agonists have demonstrated positive effects on a range of cardiovascular disease pathologies and clinical targets, including such markers of vascular inflammation as high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, and brain natriuretic peptide. Reductions in markers of dyslipidemia such as elevated levels of triglycerides and free fatty acids have also been observed, as have cardioprotective functions. Larger trials of longer duration will be required to confirm preliminary findings. In large human trials, GLP-1 receptor agonists have been associated with significant reductions in both blood pressure and weight.

Cardiovascular disease is a leading cause of death in the United States and across the world, and better therapies are constantly being sought to improve patient outcomes. Recent studies have brought our attention to the mechanisms of glucagon-like peptide 1 (GLP-1). Not only does it demonstrate beneficial effects in regard to cardiovascular risk factors (i.e., diabetes, lipid management, and weight control), but it also has been shown in animal studies to have positive cardiac effects irrespective of its effects on glucose control and weight loss. This review discusses the biology of GLP-1 and its effects on cardiovascular risk factors, and it also elaborates on the positive direct cardiovascular outcomes of GLP-1 in animal studies.

Treatment of hypertension using renal artery sympathetic denervation was first reported as early as 1924, but only recently has the advent of safer, less invasive techniques allowed this treatment modality to emerge as a promising treatment for hypertension. Aside from reductions in blood pressure, the effect of this treatment appears to be more widespread than initially thought. Renal artery sympathetic denervation may globally reduce cardiovascular risk through a variety of mechanisms such as decreased insulin resistance, oxidative stress, and organ hypertrophy, along with improvement in diastolic function and other metabolic parameters. The following is a comprehensive review of current literature on renal artery sympathetic denervation with a focus on potential cardiovascular benefits.

The role of cardiovascular risk reduction in patients with diabetes mellitus is significant as several factors have been found to promote accelerated atherosclerosis in persons with diabetes including hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. Recent attention has focused on identifying a cardiovascular biomarker that would propose a better noninvasive way to detect or visualize subclinical cardiovascular disease and prevent cardiovascular events. This article reviews the use of commonly used cardiovascular risk assessment tools and emerging biomarkers including coronary artery calcium scanning, metabolomics, genomics, and the role of optimal revascularization and risk reduction strategies and their impact on reducing risk in patients with cardiovascular disease and diabetes.

Recent studies have failed to show an improvement in cardiovascular mortality with intensive glycemic control and aggressive glycated hemoglobin (A(1c)) targets less than 7.0%. Excessive hypoglycemic episodes with intensive glucose-lowering therapy are thought to be a major factor in the failure to show cardiovascular benefit in these trials. In this article, we review the physiology of glucose metabolism, the cardiovascular pathophysiology of hypoglycemia, and the trials with an intensive glucose-lowering strategy that have studied microvascular and macrovascular complications. We also review the current non-insulin drugs available for the treatment of diabetes and their potential hypoglycemic and cardiovascular impacts.

Impaired fasting glucose (IFG) contributes to microvascular and macrovascular complications and increased cardiovascular disease risk. Although type 2 diabetes is largely considered to occur as a result of IFG, understanding of physiologic and associated management targets is uniformly lacking among health care professionals. Once definitions are standardized, diagnostic criteria and screening tools may help to identify individuals at risk sooner, thereby minimizing the rapid deterioration that often results. To counter the rising pandemic of obesity and diabetes, it is important to understand the vascular risk of IFG and impaired glucose tolerance in patients at risk.

quoted saying ‘‘you’re only as old as your arteries.’’ 4 At a pathobiological level, aortic wall stiffness has been associated with processes involving wall matrix, inflammation, and mechanical stress. Increased collagen content and extracellular matrix (arteriosclerosis) is commonly seen in hypertension and aging. In contrast, atherosclerosis relates to endovascular inflammation, increased cellular oxidative stress, and plaque formation; however, both processes can lead to increased vascular stiffness. 5 Patients with increased aortic stiffness have increased aortic pulse wave velocity and reduced arterial compliance. 6 The clinical implication of increased aortic stiffness results in increased afterload on the left ventricle; alteration in coronary perfusion, which affects cardiac diastolic relaxation; and increased myocardial oxygen consumption. Moreover, these surrogates have been tested in multiple trials with important CV outcomes data. Based on the studies so far, it is evident that increased aortic pulse wave velocity is a strong independent predictor of CV risk, regardless of whether it plays a causative role in CV risk or merely serves as a marker of CV disease already present. One example is found in the Strong Heart Study, 7 which evaluated 2405 patients without CV disease at entry with a 5-year follow-up. During this period, 344 patients had CV events that were significantly associated with high central pulse pressure, thus associating high central pulse pressure with increased arterial stiffness. 1 Another study, the Conduit Artery Function Evaluation (CAFE) trial 8 substudy (on behalf of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT] Investigators), evaluated the differential impact of BPlowering drugs on central aortic pressure and clinical outcomes. The study enrolled 2073 patients from 5 ASCOT centers after being on treatment for about 1 year. A total of 19,257 patients were enrolled in the ASCOT trial. All patients had hypertension and 3 additional risk factors. They were randomized in a 2 2 factorial design to receive 1 of 2 antihypertensive regimens: amlodipine (5 ⁄10 mg) with or without perindopril (4 ⁄8 mg) or atenolol (50 ⁄100 mg) with or without a diuretic. Despite similar brachial arm systolic BPs in the two treatment arms, there was a significant decrease in both central aortic pulse pressure and central aortic systolic pressure in the angiotensin-converting enzyme (ACE) inhibitor ⁄calcium channel blocker (CCB) arm vs the b-blocker ⁄diuretic arm. This study suggested that ACE inhibitor ⁄CCB treatment was significantly better. In addition, using the Cox proportional hazards modeling, they determined that central aortic pulse pressure was significantly associated with a post hoc‐defined composite outcome of total CV events (unadjusted P

The effect of thiazolidinediones (TZDs) on the progression of atherosclerosis in diabetes patients remains unclear. There has been heightened interest in recent years in this class of diabetes medications due to the non-glycemic lowering effects, such as altering lipids, inflammation and hematologic profiles. There have been several exciting studies over the past few years focused on the mechanism of action of the TZDs with respect to alteration in the cardio-metabolic profile in diabetes patients. New tools such as intravascular ultrasound have been used to follow plaques characteristics over time on a much more sensitive scale than has ever been possible in the past by coronary angiograms. These advances have enabled researchers to follow closely the macrovascular effects of different anti-atherosclerotic medications such as statins and TZDs. This article reviews the pathophysiology of atherosclerosis in diabetes, the role that TZDs play in this process and the imaging trials looking at the progression or regression of atherosclerosis in patients treated with TZDs.

We sought to validate that the supply-demand ratio for myocardial oxygen could be accurately measured from tracings of peripheral as well as central arterial pressure. This ratio was the ratio of the diastolic pressure-time-index (DPTI) over the systolic pressure-time index (SPTI). Sixteen patients had the peripheral DPTI/SPTI determined at cardiac catheterization by the following two different methods: (1) P 1 , using the mean diastolic and systolic peripheral arterial pressure and the ratio of the duration of diastole and systole; and (2) P 2 , where the peak systolic and diastolic peripheral arterial pressures are used, eliminating the need for planimetric data. The results of P 1 and P 2 correlated closely with the central value (r = 0.96 and 0.92, respectively). We conclude that DPTI/SPTI can reliably be measured from a tracing of peripheral arterial pressure, enabling reliable continuous monitoring of this ratio.

The ratio of the preejection period to the left ventricular ejection time (PEP/LVET), obtained from the aortic root echocardiogram, was studied immediately before and after left ventricular (LV) cineangiography in 23 patients with documented coronary artery disease. The initial PEP/LVET ratio was inversely related to LV ejection fraction (r = -.78, P less than or equal to .001). Repeat measurements taken 60 s after angiography showed a significant decrease from a mean value of .36 +/- .13 to .27 +/- .08 (P less than or equal to .005). Furthermore, when patients were divided into those with an initial PEP/LVET value above and below 0.40, those with a higher value showed a significantly greater decrease following contrast left ventriculography (mean decrease, 0.16 vs 0.06, P less than or equal to .01). This study indicates that systolic time intervals derived from echocardiography are a reliable noninvasive measure of LV function, and that ventricular function improves following left ventriculography, with the degree of improvement being inversely related to initial function.

Two patients in whom left anterior hemiblock occurred during a treadmill exercise test were found at cardiac catheterization to have significant obstruction of the proximal portion of the left anterior descending coronary artery. After successful myocardial revascularization in one of these patients, a disturbance in conduction no longer appeared during treadmill testing. To our knowledge, this association has not been previously reported, and this finding may be a useful clinical marker for significant obstructive disease of the proximal portion of the left anterior descending coronary artery.

To determine the incidence and significance of transient intraventricular conduction abnormalities occurring in association with myocardial ischemia during exercise testing, the recordings of 2,200 consecutive exercise tests were reviewed. Ten patients (0.45%) were identified as having both ischemia and intraventricular conduction abnormalities that developed transiently during the exercise test. In all 10 patients both typical angina and electrocardiographic evidence of ischemia developed during exercise. Among the 10 patients, left anterior hemiblock developed in 4, left posterior hemiblock in 2, right bundle branch block (RBBB) in 2, RBBB with left axis deviation in 1, and left anterior hemiblock progressing to complete left bundle branch block (LBBB) in 1. All 10 patients had cardiac catheterization showing significant obstruction of the left anterior descending (LAD) coronary artery at or before the origin of the first septal branch. Eight patients were treated surgically and 2 medically, all with relief of ischemic symptoms. Nine of the 10 had repeat exercise stress testing without angina or electrocardiographic evidence of ischemia and without recurrence of the transient intraventricular conduction disturbance. It is concluded that the development of transient intraventricular conduction abnormalities associated with myocardial ischemia during exercise testing is an uncommon occurrence (0.45%). When such conduction disturbances do develop, the existence of significant disease in the proximal portion of the LAD coronary artery is strongly suggested. With control of myocardial ischemia, the transient conduction disturbances during exercise are ameliorated.

Five patients had angiographically proved coronary artery aneurysms. The clinical picture was similar to that of patients with ordinary coronary artery disease. The coronary artery aneurysms were multiple and associated with extensive coronary atherosclerosis. The natural history of this condition is not known. Of the three patients treated medically and two patients treated surgically, all are alive one to two years later.

To analyze the relationship between the myocardial supply and demand for oxygen in patients with aortic regurgitation, the ratio of the diastolic pressure-time index (DPTI) over the systolic pressure-time index (SPTI) was derived from recordings of pressure during cardiac catheterization in 24 patients with aortic regurgitation, and this ratio was compared with that in 14 normal subjects and in ten patients with congestive cardiomyopathy (an ejection fraction less than 0.30). Patients with aortic regurgitation had a DPTI/SPTI of 0.75 +/- 0.06 (mean +/- SE), which was lower than in the normal subjects (1.24 +/- 0.06) and patients with cardiomyopathy (1.06 +/- 0.03) (P less than 0.001). Among the patients with aortic regurgitation, the 13 with a DPTI/SPTI below 0.70 had more severe aortic regurgitation than the 11 with a DPTI/SPTI above 0.70. Aortic regurgitation results in a reduced myocardial supply-demand ratio, as measured by the DPTI/SPTI, which is related to the severity of the valvular regurgitation and is not present in patients with left ventricular dysfunction secondary to congestive cardiomyopathy.

Left ventricular (LV) performance may remain normal in patients with LV volume overload from aortic regurgitation, but this entity results in progressive LV dysfunction. Impairment of myocardial reserve may remain undetected by current methods of assessing ventricular performance at rest, but the stress of exercise may demonstrate a reduction of myocardial reserve. To analyze the relationship between the myocardial supply and demand for oxygen in patients with aortic regurgitation, the ratio of the diastolic pressure-time index (DPTI) over the systolic pressure-time index (SPTI) was derived from recordings of pressure tracings during cardiac catheterizations in 14 patients with aortic regurgitation, and this ratio was compared with that of 24 normal subjects. The patients with aortic regurgitation had a DPTI/SPTI that fell with exercise (0.91 +/- 0.2 to 0.55 +/- 0.2) to lower values than did the ratio in the normal subjects (1.3 +/- 0.2 to 0.8 +/- 0.1) with stress. Among the patients with aortic regurgitation, a DPTI/SPTI ratio less than 0.50 with exercise identified two groups of patients that were not well separated by more common indices of severity of aortic regurgitation. The only other parameter that separated these two groups was the end-systolic volume, which is an index that reflects myocardial contractile function independent of preload. The DPTI/SPTI ratio that falls to abnormal levels with exercise may accurately reflect a failure of myocardial reserve in aortic regurgitation.