Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Statins and Dyslipidemia: Should we be Looking Beyond LDL?

Source: Boekholdt SM, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: A meta-analysis. 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 cholesterol (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.

Broadening Perspectives on Maintaining Healthy Erectile Function

Source: Meldrum DR, et al. Lifestyle and metabolic approaches to maximizing erectile and vascular health. 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.

When Thiazides are Associated with Hyponatremia

Source: Rastogi D, et al. Evaluations of hospitalizations associated with thiazide-associated hyponatremia. 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.