Prediabetic Neuropathy: Does It Exist?

It is now increasingly being appreciated that a substantial proportion of subjects with prediabetes may exhibit peripheral neuropathy and/or neuropathic pain. The reverse is also true, inasmuch as examining patients with idiopathic peripheral neuropathy will frequently reveal prediabetes. In the general population, the prevalence of neuropathy in prediabetes is intermediate between overt diabetes and subjects with normoglycemia. This prediabetic neuropathy is, generally, milder in comparison to diabetic neuropathy and mainly affects small fibers mediating sensory function. Hyperglycemia, microangiopathy, dyslipidemia and the metabolic syndrome have been implicated as pathogenic mechanisms. In practice, therapy of prediabetic neuropathy should be addressed towards normoglycemia and correction of cardiovascular risk factors. However, additional work is needed to establish the long-term results of this approach.     

Lethal Reperfusion Injury: Does It Exist and Does It Matter?

Journal of Thrombosis and Thrombolysis -     

Reperfusion Injury: Does It Exist and Does It Have Clinical Relevance?

Although reperfusion is an absolute prerequisite for the survival of ischemic tissue, it is not necessarily without hazard. Many (but not all) cardiologists are of the opinion that some components of reperfusion may be detrimental and able to inflict injury over and above that attributable to the ischemia. In this article we define four sequelae of reperfusion that might be designated as reperfusion injury. We identify possible underlying mechanisms and consider whether any of these forms of reperfusion injury are of clinical relevance.     

Statin Adherence: Does Gender Matter?

Purpose of Review

Cardiovascular disease (CVD) continues to be the leading cause of death for men and women in the USA. Statins have contributed significantly to noted declines in cardiovascular-related mortality in the last decade; however, the benefit of statins is inequitable across genders. Women continue to be less likely to take statins and to meet target LDL goals than men. As a possible contributing factor to this disparity, we explore the evidence for gender-based differences in provision of, and adherence to statins.

Recent Findings

Compared with men, women are less likely to adhere to statins. Potential reasons for this gender difference in use of statins can be observed across all phases of adherence including both intentional and unintentional non-adherence. Notable gender-specific contributing factors for statin non-adherence include decreased provider and patient awareness of CVD risk among women, higher risk of statin intolerance among women, and competing demands associated with family caregiving responsibilities. Similar to limitations in the broader CVD literature, there is inadequate inclusion of gender-specific analyses in statin-related trials.

Summary

Gender-based disparities in statin adherence can be linked to both provider level, psychosocial, and medication intolerance factors. Interventions designed to improve statin adherence should take gender-specific challenges into consideration such as women being older at the time of increased CVD risk, higher rates of statin intolerance, and potentially greater caregiving responsibilities.

     

Lethal Myocardial Reperfusion Injury: Does it Exist; Should We Treat It?

Journal of Thrombosis and Thrombolysis -     

Does Reperfusion Injury Exist?

Journal of Thrombosis and Thrombolysis -     

Does Idiopathic Cough Exist?

Despite a meticulous protocol involving diagnostic testing and trials of empirical therapy, there may be no obvious cause for a chronic cough in up to 42% of cases referred for specialist evaluation. In some cases, failure to consider causes that include the asthma/eosinophilic airway syndromes such as eosinophilic bronchitis and atopic cough, or nonacid gastroesophageal reflux disease may explain diagnostic failure. However, a distinct group of patients may be considered to have true idiopathic cough. Current published evidence suggests a certain patient phenotype, namely, middle-aged females with prolonged nonproductive cough and cough reflex hypersensitivity. Almost nothing else is known about this clinical entity and currently no specific therapy exists.     

Antihypertensive Treatment: Does the J-curve Exist?

In the treatment of arterial hypertension, the optimal reduction in blood pressure is obviously the one that causes the maximum achievable prevention of hypertension-associated cardiovascular morbidity and mortality. This goal has clearly not been reached by today's approach to the treatment of elevated blood pressure. Treated hypertensive patients are still at increased risk of cardiovascular morbidity and mortality in spite of receiving antihypertensive treatment, as shown in many intervention studies.One possible explanation for this outcome could be that treated blood pressure is rarely brought down to strictly normotensive levels, again as shown in numerous studies. This finding would suggest that a more vigorous lowering of blood pressure would be advantageous when treating hypertensive patients. On the other hand, the fact that the relationship between the level of blood pressure and risk is J-shaped obviously means that vigorous lowering of blood pressure may increase cardiovascular risks, if blood pressure is brought down too far.Several open, retrospective, nonrandomized studies have been analyzed with this issue in mind, but so far only two prospective intervention trials have been specifically designed to address this problem: the BBB Study, published in 1994, and the much larger HOT Study, published in 1998. The rationale of these studies as well as some of their findings will be discussed briefly here, with emphasis on the HOT Study.     

Statin escape phenomenon: Does it really exist?

BACKGROUND: The normalization of blood lipid profile has become an accepted method of primary and secondary prevention of vascular disease, with statins being the most popular group of medicines prescribed to lower cholesterol and LDL cholesterol levels. The failure of statins, administered in an appropriate dose, to maintain the optimal level of LDL cholesterol is a rare phenomenon, and is still not well understood in patients compliant for both medication and diet. The entity of "statin escape phenomenon", proposed to explain the failure of statins in some of these patients, has not been studied or characterized extensively, and reports of its prevalence are scarce. METHODS: Patients with hyperlipidemia type 2a or 2b who had been treated with statins for at least 1 year and who were followed up in the lipid clinic on a regular basis every 3-4 months were included in this study. The charts of patients whose LDL cholesterol levels were elevated by 15% or more while receiving the same treatment were analyzed, and patients with putative statin escape phenomenon were included in the study and further characterized. RESULTS: Forty-five of 358 statin-treated patients demonstrated a 15% increase in LDL cholesterol levels, leading to suspicion of statin escape phenomenon. However, a strict exclusion analysis left only two patients without evident potential triggers for the observed elevation in LDL cholesterol. CONCLUSIONS: Whether a statin escape phenomenon really exists is still not certain, but if it does exist, it is probably an uncommon event with a low prevalence.     

College Binge Drinking: What Is It? Who Does It?

This article presents research included in the symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. James Lange was the organizer and provided the introduction of this article. Gayle Boyd was the chairperson, and Mary Larimer was the discussant. The presentations were (1) Defining binge-drinking quantities through resulting BACs, by James E. Lange and Robert B. Voas; (2) Environmental predictors of heavy episodic drinking events, by John D. Clapp; (3) Parents' continuing role in college binge drinking, by Rob Turrisi, Racheal Taki, and James Jaccard; and (4) Motivations of binge drinkers, by Mark B. Johnson, Robert B. Voas, and James E. Lange. The summary and discussion were provided by Mary Larimer.     

Statin therapy in renal disease: Harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit, if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.     

Does Lethal Myocardial Reperfusion Injury Exist?

Journal of Thrombosis and Thrombolysis -     

Pre‐clinical Dementia: Does it Exist?

Abstract . Identification of syndromes that will progress to dementia carries immense importance for the management of these diseases when therapies are available and for future research into effective early prevention. Evidence supporting the presence of a preclinical phase for dementia has arisen from a range of different areas. Clinical and epidemiological studies have identified both cognitive and neurological abnormalities which predict the future development of dementia. Similarly, various neuroimaging techniques have identified abnormalities in asymptomatic subjects with significant risk for developing Alzheimer's disease and subjects who show mild cognitive deficits. Neuropathological series are hampered by non‐representative study populations and poor antemortem data but in studies where informants have been utilised to provide details of subjects' antemortem cognitive function, evidence indicates that the presence of brain pathology is associated with cognitive deficits. This paper reviews the current literature exploring the presence of a pre‐clinical phase for dementia, identifies the weaknesses in this research and provides suggestions for future research.     

Statin therapy in renal disease: Harmful or protective?

Chronic kidney disease (CKD) creates one of the highest-risk atherosclerotic states that can occur in human beings. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has gained widespread acceptance in the general population for the purposes of lowering low-density lipoprotein cholesterol (LDL-C) and reducing the future risks of myocardial infarction, stroke, and cardiac death. In patients with CKD, these benefits are believed to be enjoyed to the same or greater degrees. Reductions in LDL-C with statins may be associated with a reduced progression of CKD. Importantly, recent studies suggest statins are associated with a reduction in rates of acute renal failure after cardiopulmonary bypass surgery and exposure to iodinated contrast. In patients with end-stage renal disease (ESRD), recent data suggest that the annual rate of coronary artery calcification can be attenuated or reduced with LDL-C reduction. However, two large trials demonstrating LDL-C reduction with statins and with these drugs have failed to demonstrate a reduction in cardiovascular events in ESRD. Thus, the potential benefits of statins and LDL-C reduction in CKD have to be considered in light of evidence suggesting a reduced benefit if any, in patients with ESRD. In addition, studies suggest that there are higher adverse drug effects with statins in CKD.