Can Ischemic Stroke Be Caused by Acute Reduction of Blood Pressure in the Acute Phase of Cardiovascular Disease?

Acute-phase cardiovascular disease (CVD) frequently presents with markedly elevated blood pressure (BP) levels and often requires fairly rapid lowering of BP. On the other hand, aggressive lowering of systemic BP to the point that the cerebral BP decreases below a certain threshold may result in ischemic stroke. The authors retrospectively studied 192 consecutive patients with CVD who had markedly elevated BP and end-organ damage. Ischemic stroke was noted in 12 of these patients during BP-lowering therapy. The incidence of ischemic stroke did not differ significantly between a standard BP-lowering group, in which the target BP reduction was within the parameters of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, and a rapid BP-lowering group, in which the target BP was below these guidelines (7.1% vs 2.6%, respectively; P=.27, not significant). In stepwise multiple regression analysis, diabetes mellitus (beta=0.203, P=.008) and acute pulmonary edema (beta=0.228, P=.003) remained significant factors associated with the incidence of stroke. Thus, acute pulmonary edema and diabetes were the most important factors related to ischemic stroke during BP reduction in patients with marked elevations of BP regardless of the rapidity of BP lowering.     

Abdominal Obesity and Cardiovascular Disease: Is Inflammation the Missing Link?

It is well established that cardiovascular disease has an inflammatory component. The present narrative review explores the role of adipose tissue distribution, morphology, and function as potential mediators of the link between inflammation and cardiovascular disease. Evidence that abdominal obesity is a key driving force behind a constellation of atherothrombotic inflammatory abnormalities linked to insulin resistance and often referred to as the metabolic syndrome is also reviewed. It is also proposed that the amount of visceral adipose tissue and the liver fat content are important factors responsible for the link between abdominal obesity and features of the metabolic syndrome. It is suggested that the inflammatory profile associated with excess visceral adipose tissue/liver fat may be a consequence of the relative inability of subcutaneous adipose tissue to expand through hyperplasia and to act as a protective metabolic sink storing the chronic energy surplus resulting from a positive energy balance (overnutrition or lack of physical activity or both). In this model, the inflammatory profile often observed among sedentary overweight/obese individuals with an excess of visceral adipose tissue/liver fat may be a consequence of a more primary defect in subcutaneous adipose tissue. On that basis, it is proposed that therapeutic strategies relieving the stress for storage of a chronic energy surplus in the subcutaneous adipose tissue (reduced caloric intake, increase in energy expenditure, pharmacotherapy) should induce a substantial loss of visceral adipose tissue and of ectopic fat depots such as the liver, thereby substantially reducing inflammation.     

The Incidence and Pathophysiology of the Obesity Paradox: Should Peritoneal Dialysis and Kidney Transplant Be Offered to Patients with Obesity and End-Stage Renal Disease?

Purpose of Review

To educate nephrologists and primary-care physicians about the incidence, pathophysiology, and survival benefits of the obesity paradox in end-stage renal disease (ESRD). This review also discusses the future of kidney transplant and peritoneal dialysis in obese dialysis patients.

Recent Findings

Obesity paradox in ESRD was first reported three decades ago, and since then, there have been several epidemiological studies that confirmed the phenomenon. Regardless of the anthropometric indices used to define obesity in ESRD patients, these markers serve to predict the dialysis patient’s survival. The pathophysiology of obesity paradox tends to be multifactorial. Recent cohort studies demonstrated a survival benefit in all race and ethnic groups, but Hispanics and blacks experienced increased survival rates when compared to non-Hispanic whites. Obese dialysis patients should be offered peritoneal dialysis, especially if they are new to dialysis and have an adequate renal residual function. Several studies have shown that the benefit of receiving kidney transplant in obese patients exceeds the risks. The robotic-assisted kidney transplant (RAKT) procedure is the latest innovation that could offer hope for obese dialysis patients who have been denied or are waiting for kidney transplant.

Summary

The obesity paradox phenomenon in ESRD is a unique illustration of survival benefit in a population that has a high overall annual mortality. Peritoneal dialysis should be encouraged for obese patients who have preserved residual renal function. Kidney transplant centers should encourage RAKT utilization in obese dialysis patients instead of denying them a kidney transplant.

     

Projected Cardiovascular Impact of Obesity in Children and Adolescents: Will Obesity Increase the Cardiovascular Risk of Women to That of Men?

Far too many girls suffer from overweight, obesity, and even severe obesity in childhood and adolescence. The early establishment of excess adiposity is associated with the development of cardiovascular disease (CVD) through complex metabolic aberrations that manifest as components of the metabolic syndrome at young ages. When combined with exposure to other independent CVD risk factors, overweight and obese girls face an elevated risk of cardiovascular morbidity and mortality in adulthood. Additionally, due to their reproductive capacity, women face a different series of risks with regards to the development of CVD compared with men. The risk of CVD accumulates across the lifespan of women, and without a special emphasis in terms of prophylaxis and treatment in younger girls and women, their risk of CVD is likely to equal or even surpass that of men in the future.     

The Alzheimer’s Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar

Aging-related cellular and molecular processes including low-grade inflammation are major players in the pathogenesis of cardiovascular disease (CVD) and Alzheimer’s disease (AD). Epidemiological studies report an independent interaction between the development of dementia and the incidence of CVD in several populations, suggesting the presence of overlapping molecular mechanisms. Accumulating experimental and clinical evidence suggests that amyloid-beta (Aβ) peptides may function as a link among aging, CVD, and AD. Aging-related vascular and cardiac deposition of Αβ induces tissue inflammation and organ dysfunction, both important components of the Alzheimer’s disease amyloid hypothesis. In this review, the authors describe the determinants of Aβ metabolism, summarize the effects of Aβ on atherothrombosis and cardiac dysfunction, discuss the clinical value of Αβ1-40 in CVD prognosis and patient risk stratification, and present the therapeutic interventions that may alter Aβ metabolism in humans.     

Does an Obesity Paradox Really Exist After Cardiovascular Intervention?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies

Several studies have shown the existence of an obesity paradox after Percutaneous Coronary Intervention (PCI). However, other studies have shown its absence. This study sought to perform a systematic review and meta-analysis of studies comparing the mortality risk between high body mass index patients and normal weight patients after PCI.We have searched PubMed, Embase, and Chinese medical journal for randomized controlled trials (RCTs) and observational studies published between the year 2000 and 2015 by typing the keywords “percutaneous coronary intervention” and “obesity paradox.” The main outcome was “all-cause mortality”. RevMan 5.3 software was used to calculate the risk ratio (RR) with 95% confidence interval (CI) to express the pooled effect on discontinuous variables.Twenty-two studies have been included in this meta-analysis consisting of a total of 242,377 patients with 73,143 normal weight patients, 103,608 overweight, and 65,626 obese patients. Younger age, higher cardiovascular risk factors and the intensive use of medications have mainly been observed among obese patients followed by overweight and normal weight patients respectively. In-hospital, 12 months and ≥ 1 year (long-term) mortality risks were significantly lower in the overweight and obese groups with (RR: 0.67; 95% CI: 0.63–0.72, P < 0.00001) and (RR: 0.60; 95% CI: 0.56–0.65, P < 0.00001) respectively in the in-hospital follow-up (RR: 0.62; 95% CI: 0.55–0.71 and 0.57; 95% CI: 0.52–0.63, P < 0.00001) at 12 months, and (RR: 0.70; 95% CI: 0.64–0.76; P < 0.00001) and (RR: 0.80; 95% CI: 0.71–0.91, P = 0.0006) respectively for the long-term follow-up after PCI.This “obesity paradox” does exist after PCI. The mortality in overweight and obese patients is really significantly lower compared to the normal weight patients. However, the exact reasons for this phenomenon need further exploration and research in the future.     

The Role of Calcium in the Prevention of Cardiovascular Disease—A Review of Observational Studies and Randomized Clinical Trials

Calcium is a mineral that is important for bone health and has also been suggested to play a role in the prevention of cardiovascular disease (CVD). Lately, the potential effects of both inadequate and excessive calcium intake have received growing attention. In this review, we summarize the evidence from experimental, epidemiologic, and clinical studies investigating the role of calcium intake, either from the diet or from supplements, as well as blood concentrations, in relation to the risk of CVD in adults. In vitro and in vivo laboratory studies suggest that calcium may be involved in CVD development through multiple pathways, including blood cholesterol, insulin secretion and sensitivity, vasodilation, inflammatory profile, thrombosis, obesity, and vascular calcification. Several prospective epidemiologic studies have examined how dietary or supplemental calcium intake is associated with CVD incidence or mortality in middle-aged and older adults, and the results are inconsistent. Prospective studies investigating blood concentrations of calcium have also reported mixed results. However, changes in blood calcium concentrations may reflect a disturbed calcium phosphate balance, which is associated with increased risk of CVD. To date there is no randomized clinical trial that has been designed specifically to test the effect of calcium supplementation on the risk of CVD as the primary end point. Existing trials have performed secondary analyses, and most of them have been conducted among postmenopausal women. These trials suggest that calcium supplementation has no effect on CVD development; however, they do not allow a definitive conclusion to be drawn. The average daily intake of calcium is low in many populations; however, the evidence for a potential role of dietary or supplemental calcium in the prevention of CVD remains insufficient and inconclusive. Only large-scale randomized trials designed to investigate the effects of calcium supplementation on CVD events as the primary end point, as well as short-term trials investigating the effect on coronary biomarkers, can provide a definitive answer.     

Cardiovascular Disease in Blacks: Can We Stop the Clock?

Blacks have the highest rates of hypertension and cardiovascular disease, with earlier onset, greater severity, and more target organ damage including coronary disease, heart failure, stroke, and end-stage renal disease. A major reason is the greater prevalence of other cardiovascular disease risk factors, particularly obesity, inactivity, and diabetes mellitus, along with socioeconomic differences, adherence, and achievement of goals. This review focuses on the burden of cardiovascular disease in blacks. Therapeutic lifestyle changes and pharmacologic interventions to decrease clinical events in this high-risk group are described. Intensive blood pressure control is a primary means of "stopping the clock" in the progression of cardiovascular disease and renal disease. Thiazide diuretics remain primary first-step agents, especially for uncomplicated hypertension; calcium channel blockers are also efficacious. However, renin-angiotensin system modulators may also be beneficial, especially with a diuretic, considering the high prevalence in this group of patients of compelling indications for use of such agents.     

Navigating the “MACE” in Cardiovascular Outcomes Trials and decoding the relevance of Atherosclerotic Cardiovascular Disease benefits versus Heart Failure benefits

The publication of results from recent cardiovascular outcome trials (CVOTs) has transformed the landscape of diabetes treatment. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose co-transporter-2 (SGLT2) inhibitors have demonstrated CV benefits in large, well-conducted, randomized studies. Today, empagliflozin, canagliflozin and liraglutide are US Food and Drug Administration-approved not only for glucose-lowering, but also to reduce the risk of cardiovascular (CV) events/CV mortality in people with type 2 diabetes (T2DM) and established CV disease (CVD)/high CVD risk. Although the CVOTs were primarily powered for CV safety (non-inferiority), they also demonstrated CV efficacy (superiority). This initially surprised many in the diabetes community, but the replication of the CV benefits with different compounds in the same class alleviated concerns about the CV benefits being chance findings. However, many questions remain. While the heterogeneity in the CV benefits in the various CVOTs can be attributed to the variability in CV risk in the different studies, the reason(s) for the differences in the CV benefits between the GLP-1RA class and the SGLT2 inhibitor class appear to be more complex. An analysis of major adverse cardiovascular events (MACE) in the CVOTs shows that the CV benefits of GLP-1RAs are predominantly specific to atherosclerotic CV events (non-fatal myocardial infarction [MI], non-fatal stroke and CV death). By contrast, the SGLT2 inhibitors do not have any significant effects on atherosclerotic CV events (non-fatal MI/stroke). Their benefits are predominantly on hospitalization for heart failure (HF), suggesting effects primarily on myocardial function (“the pump”), and not on the “pipes” (coronary arteries). In the present review, we discuss the rationale for the conduct of CVOTs, highlight the inability of the classic three-point MACE to capture the entire spectrum of atherosclerotic and non-atherosclerotic CVD morbidity, especially HF in T2DM, and discuss the results of the CVOTs with a focus on the clinical significance of atherosclerotic CVD (ASCVD) versus HF, which develops in a sizeable proportion of people with diabetes and without prior ASCVD.     

Rethinking Ormond’s Disease: “Idiopathic” Retroperitoneal Fibrosis in the Era of IgG4-Related Disease

Idiopathic retroperitoneal fibrosis (RPF) is a periaortic sclerotic disease that encases adjacent retroperitoneal structures, particularly the ureters. A subset of idiopathic RPF cases can be associated with IgG4-related disease, but the frequency of this association is not clear. We selected 23 cases of idiopathic RPF and identified IgG4-related RPF cases based on the presence of IgG4+ plasma cells in the tissue, using an IgG4/IgG ratio cutoff of >40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review.We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar.IgG4-related disease accounts for a substantial percentage of patients with “idiopathic” RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic.