Panteleimon A. Sarafidis

Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/ insulin resistance?

The prevalence of hypertension in individuals with obesity or type II diabetes is substantially elevated. Increased levels of non-esterified fatty acids (NEFAs) in abdominally obese subjects were reported to contribute in the development of various disturbances related to the metabolic syndrome, such as hepatic and peripheral insulin resistance (IR), dyslipidaemia, β-cell apoptosis, endothelial dysfunction and others. However, the involvement of NEFAs in the development of hypertension has been much less studied in comparison to other mechanisms linking IR and central obesity with blood pressure (BP) elevation. This article reviews the existing evidence on the relation between NEFA and hypertension in an attempt to shed a light on it. In vivo data from both animal and human studies support that acute plasma NEFA elevation leads to increase in BP levels, whereas epidemiological evidence suggests a link between increased NEFA levels and hypertension. Further, accumulating data indicate the existence of several pathways through which NEFAs could promote BP elevation, that is α1-adrenergic stimulation, endothelial dysfunction, increase in oxidant stress, stimulation of vascular cells growth and others. The above data support a possible important role of NEFA in hypertension development in patients with obesity and the metabolic syndrome and raise hypotheses for future research.

Antihypertensive Therapy and the Risk of New-Onset Diabetes

Numerous studies have consistently demonstrated that certain classes of antihypertensive medications have differential effects on carbohydrate and lipid metabolism in humans. In general, higher doses of thiazide diuretics (i.e., ≥25 mg/day hydrochlorothiazide) and β-blockers, at any antihypertensive dose, worsen glycemic control, with β-blockers worsening insulin sensitivity (1). Conversely, ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers (CCBs) have neutral or beneficial effects on these variables (2,3). It is noteworthy, however, that not all drugs within the same class have similar effects on insulin sensitivity. This is exemplified by the effects of vasodilating β-blockers failing to worsen insulin resistance and consequently having neutral effects on glycemic control (4,5).nnThese aforementioned observations are evident in 11 randomized clinical outcome trials where development of new-onset diabetes was evaluated as a secondary end point (Table 1) (6–11). In contrast to this general trend, the STOP-2 (Swedish Trial in Old Patients with Hypertension 2) reported no difference in diabetes incidence between conventional treatment (β-blockers or diuretics) and either ACE inhibitor–or CCB-based treatment (12). Moreover, in addition to prospective randomized trials, some long-term epidemiological studies, such as the ARIC (Atherosclerosis Research in Communities) study, have linked different classes of antihypertensive agents with development of new-onset diabetes (13).nnAll of these studies, however, have limitations to their conclusions. First, all had cardiovascular outcomes rather than incidence of new-onset diabetes as a primary end point. Second, it is difficult to assess the effects of a single class of agents since many studies …

Do the Metabolic Effects of β Blockers Make Them Leading or Supporting Antihypertensive Agents in the Treatment of Hypertension

Reduction of blood pressure to guideline goals (i.e., <130/80 mm Hg) in persons with diabetes is crucial to optimally reduce cardiovascular events and kidney disease progression. Since many patients will be >20/10 mm Hg above this goal, most guidelines recommend using agents that block the renin–angiotensin system in concert with a thiazide‐like diuretic to achieve goal blood pressure. Meta‐analyses of clinical trials indicate that while all classes of antihypertensive agents reduce cardiovascular risk, they exert different effects on glucose utilization and lipids and, hence, may affect morbidity. Specifically, β blockers, in general, worsen insulin resistance and increase triglycerides in a dose‐dependent fashion. Moreover, they are not recommended as initial therapy for hypertension treatment in the absence of heart failure or recent myocardial infarction, especially in the elderly. Recent studies support the notion that newer β blockers with vasodilating effects have a better metabolic profile when compared with those that purely affect β receptors. Thus, vasodilating β blockers, by being neutral on glycemic and metabolic factors, are associated with less use of additional medication for lipid or glucose control and may provide a potentially greater cardiovascular risk reduction by virtue of these effects.

Level of Kidney Function Determines Cardiovascular Fate After Coronary Bypass Graft Surgery

The traditional risk factors for cardiovascular (CV) disease, ie, hypertension, diabetes, or metabolic syndrome, are also risk factors for chronic kidney disease development.1 For more than a quarter of a century, the association between late-stage kidney disease, ie, glomerular filtration rate (GFR) <30 mL/min, and higher CV death rate has been recognized.2 Only recently, however, have studies in the general population3–5 and in cohorts with previous CV events6 linked the continuum of increasing CV risk with decreasing kidney function. This is related in part to the fact that current studies used validated formulas derived from kidney disease outcome trials7,8 to find an estimated GFR (eGFR) rather than simply measuring serum creatinine randomly.nnArticles pp 1056 and 1063 nnAll studies published within the last decade indicate that when GFR falls to <60 mL/min (stage 3 nephropathy), a significant increase in CV events occurs.5,6 This may relate to the fact that as GFR falls to <60 mL/min, many physiological and regulatory functions of the kidney start to wane; such functions include reductions in 1,25[OH] vitamin D and erythropoietin synthesis. …

Cardiovascular disease in CKD in 2014: New insights into cardiovascular risk factors and outcomes

Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascular events and cardiovascular mortality. During 2014, several research efforts focused on clarifying the complex pathophysiology, assessing the prognostic associations and improving the treatment of cardiovascular disease in patients with CKD.