Statins and Dyslipidemia: Should we be Looking Beyond LDL?
Source: Boekholdt SM, et al. JAMA 2012;307:1302-1309.
Treatment of dyslipidemia with statins produces consistent, durable lowering of low-density lipoprotein cholesterol (LDL-C), which is associated with substantial reductions in myocardial infarction and stroke. Other lipoprotein markers — in particular apolipoprotein B (apoB) and non-high-density lipoprotein cholester ol (non-HDL-C) — are also associated with vasculopathy. Indeed, the putative pathogenetic role of apoB has garnered some enthusiasm from lipidologists who encourage more routine measurement and modulation of apoB as a primary goal.
Risk reduction with statins is imperfect. That is, substantial risk for vascular events and death exists even with excellent LDL-C reduction. Might levels of apoB or non-HDL-C in patients already on a statin help us to discern which ones remain at high risk?
Boekholdt et al performed a meta-analyis of statin trials (n = 62,154) that included data on apoB and non-HDL-C, examining the relationship between on-treatment levels of LDL-C, apoB, non-HDL-C, and cardiovascular outcomes. For each increase of one standard deviation in the level of any of these three markers, the risk for a cardiovascular event increased, and to a very similar degree (13%-16% increase per standard deviation). However, when comparing the three markers with one another, non-HDL-C showed a statistically significantly greater association with increased risk than the other two markers. The authors suggest that based on this and other data, stronger consideration should be given to promoting non-HDL-C as an important target for reduction in subjects with dyslipidemia.
When Thiazides are Associated with Hyponatremia
Source: Rastogi D, et al. J Clin Hypertens 2012;14:158-164.
Control of hypertension is rewarded with important reductions in myocardial infarction, stroke, and cardiovascular death. Yet, the job of hypertension control is daunting, since on a worldwide basis it is estimated that more than one-fourth of all adults have hypertension! It has been known for more than 5 decades that thiazides can produce electrolyte disarray, including hypokalemia, hyponatremia, and hypomagnesemia, any of which can result in serious adverse effects and/or hospitalization. Rastogi et al performed a retrospective case-control study to elucidate risk factors for hyponatremic hospital admission while on a thiazide diuretic. They compared 1802 cases of hospitalized thiazide-associated hyponatremia with controls (n = 9003).
Risk for hyponatremic hospitalization doubled with each 10-year increase in age. The only other statistically significant associations were coadministration of an ACE inhibitor and concomitant hypokalemia. The coadministration of an ARB had a strong trend toward increased risk, but was marginally non-significant. Patients with comorbid diabetes, dyslipidemia, and gastroesophageal reflux disease were also more likely to be admitted for hyponatremia. Hopefully, recognition of these associations will assist clinicians to prevent hyponatremia, or at least detect its presence earlier.
Broadening Perspectives on Maintaining Healthy Erectile Function
Source: Meldrum DR, et al. Int J Impot Res 2012;24:61-68.
For more than a decade, it has been recognized that nitric oxide (NO) is critical in the attainment and maintenance of an erection. Accordingly, pathology that induces endothelial dysfunction, and hence impaired generation of NO, is consistently associated with erectile dysfunction (ED). Traditional cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and cigarette smoking are each associated with increased prevalence and incidence of ED. Increases in oxidative stress appear to be a common denominator for many of the paths that lead to endothelial dysfunction.
Additional lifestyle factors that have been associated with endothelial dysfunction include insufficient exercise, obesity, and specific dietary components (e.g., high carbohydrate diet).
Many of the risk factors associated with endothelial dysfunction are modifiable. For instance, obesity is associated with insulin resistance, which lowers vascular NO. Exercise improves NO levels systemically. A high-fat intake may increase oxidative vascular wall stress.
There is some literature support for multifactorial intervention in men with ED to help restore sexual function. Meldrum et al suggest a list of factors that might favorably impact endothelial health (and hence, sexual functionality), including: 1) maintenance of healthy weight; 2) regular aerobic exercise; 3) low-fat, low glycemic-index diet; 4) smoking cessation; 5) alcohol moderation; 6) folate and omega-3 fatty acid supplementation; and 7) ARB rather than ACE treatment of hypertension.
Cancer Risks Associated with Diagnostic X-rays
Source: Linet MS, et al. CA Cancer J Clin 2012;62:75-100.
Within a few years after the initiation of diagnostic X-rays, toxic effects were noted, including increased risk for skin cancer, leukemia, dermatitis, and cataracts. In this early period, doses of X-ray, especially from fluoroscopy, were high. Protective devices for patients as well as persons occupationally exposed to diagnostic radiation demonstrably reduced such adverse consequences.
The dose of radiation that is required to induce cancer is not clearly known. However, populations who have been exposed to calculable levels of radiation through wartime exposure (i.e., Japanese atomic bomb survivors) and subjects receiving radiation therapy help us to predict a dose-response relationship. It is not yet clear to what extent the high-dose radiation exposure and subsequent development of cancer reflects cumulative lower dose exposures. Nonetheless, because radiation toxicity may be related to total exposure, peak exposure, or both, radiation from commonly used diagnostic procedures has stimulated concern.
For instance, a CT of the abdomen, commonly used investigationally for persons with acute or chronic abdominal pain, incurs the same amount of radiation exposure as 750 chest X-rays. Linet et al quote recent estimates suggesting that the 70 million CT scans performed each year in the United States could lead to 29,000 additional cancers.
The authors recommend a number of steps to reduce unnecessary radiation exposure, including 1) learning about radiation doses associated with various imaging techniques, 2) consideration of imaging without radiation (i.e., ultrasound, MRI), and 3) avoidance of elective X-rays in pregnant women.
The REDEEM Trial: Dutasteride for Management of Localized Prostate Cancer
Source: Fleshner NE, et al. Lancet 2012; 379:1103-1111.
Prostate cancer (pca) comprises 25% of all newly diagnosed cancers in men in the United States. PCA chemoprevention trials with 5-alpha-reductase inhibitors have had mixed results. The first major PCA prevention trial with finasteride showed a 25% decrease in total PCA vs placebo, but an increase in more aggressive (high Gleason score) cancers. A similarly designed large prevention trial with dutasteride again found a 25% decrease in total PCA, but there was an increase in more aggressive cancers (albeit not statistically significant in this trial). Based on these mixed results, clinicians have been reluctant to use 5-alpha-reductase inhibition for PCA prevention.
Might 5-alpha-reductase inhibitors prove more useful for treatment of PCA rather than prevention? The REDEEM trial randomized men with localized PCA (n = 300) who had elected active surveillance for their disease to dutasteride 0.5 mg/d or placebo. At 3 years time, the risk of PCA progression was reduced by 38% in men on dutasteride.
Because dutasteride is generally well tolerated, men with non-aggressive Gleason scores (six or less) who might otherwise select active surveillance for localized disease may have reduced risk of disease progression with the addition of dutasteride.
Amantadine for Traumatic Brain Injury
Source: Giacino JT, et al. N Engl J Med 2012;366:819-826.
In young adults (age 15-30), traumatic brain injury (TBI) is the most common cause of death and disability. As many as one in seven TBI hospital admissions leaves the hospital in a vegetative state. Amantadine (AMT) has achieved some popularity for inclusion in pharmacotherapy regimens for disorders of consciousness, although the mechanism by which AMT effects positive change is uncertain. Certainly it has been shown that AMT blocks N-methyl-D-aspartate, and is an indirect agonist of dopamine, but what these pharmacologic effects do to enhance outcomes is unclear. In any case, initial trials have supported its use, and a major observational trial indicated better outcomes in TBI for persons who had received AMT.
Patients who had sustained TBI (n = 184) and who were either vegetative or minimally conscious for at least 1 month (and no longer than 16 weeks) after injury were randomized to AMT or placebo. AMT was administered initially at 100 mg b.i.d., and titrated to 200 mg b.i.d. if the Disability Rating Scale had not shown improvement. The course of treatment was 4 weeks in duration, and patients were monitored for 2 weeks after continuation of treatment.
AMT treatment was associated with statistically significantly better functional recovery outcomes than placebo. AMT is not a new medication, so its adverse effects profile, characterized by mild, transient adversities, is well known. These data support the inclusion of AMT in the pharmacologic regimen of serious TBI.
Statins and Dyslipidemia: Should we be Looking Beyond LDL?; When Thiazides are Associated with Hyponatremia; Broadening Perspectives on Maintaining Healthy Erectile Function; Cancer Risks Associated with Diagnostic X-rays; The REDEEM Trial: Dutasteride for Management of Localized Prostate Cancer; Amantadine for Traumatic Brain InjuryYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content