Clinical Briefs in Primary Care
February 1, 2009 6 minutes read
White coat hypertension and Type 2 diabetes
Source: Kramer CK, et al. Impact of white coat hypertension on microvascular complications in Type 2 diabetes. Diabetes Care 2008;31:2233-2237.
The preponderance of evidence about the impact of hypertension (HTN) on CV and renal (CV&R) endpoints is based upon measurement of BP in the office. For more than 3 decades, HTN specialists have recognized that office BP is only one way to view the burden of HTN. Indeed, either 24-hr ambulatory BP monitoring or even home BP self-monitoring correlates better with CV&R endpoints than office BP. One explanation for the inaccuracy of office BP is that some patients' BP rises when in the medical setting, yet remains essentially normal at other times: white coat hypertension (WCH). Although some examiners have pointed out that WCH portends enhanced proclivity to develop frank hypertension, and ought to be considered of greater importance when target organ damage is present, others have opined that WCH exists, but if BP is otherwise normal, no intervention (save enhanced vigilance for the development of frank HTN) is necessary.
Kramer et al studied a population of Type 2 diabetics (DM2) comparing the prevalence of nephropathy and retinopathy in persons with WCH (n = 46) as compared to normotensives (n = 117).
DM2 subjects with WCH had a 2 times greater prevalence of nephropathy and 2.7 times greater prevalence of retinopathy (adjusted for confounders). Although the pathogenetic role played by WCH remains controversial, the associations discerned in this observational study merit concern.
Vitamin K and insulin resistance
Source: Yoshida M, et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008;31:2092-2096.
Clinicians traditionally associate vitamin K (VitK) with the coagulation system, especially as it relates to antithrombotic therapy with agents like coumadin. Although a biologically plausible mechanism remains to be identified, a recent observational study reported a positive linear relationship: Higher amounts of dietary or supplemental VitK were associated with higher insulin sensitivity. Another small study indicated better glucose disposal (through better insulin sensitivity) after VitK supplementation in healthy men.
To investigate this phenomenon further, Yoshida et al studied healthy, non-diabetic adults (age 60-70; n = 355) by comparing levels of insulin resistance before and 36 months after VitK supplementation or placebo.
At the trial end, no changes were seen in levels of insulin resistance among female subjects. On the other hand, male subjects evidenced a statistically significant improvement in insulin resistance. Whether VitK supplementation might have a salutary effect in diabetics or others with overt insulin resistance syndromes (e.g., impaired glucose tolerance, obesity, polycystic ovary syndrome) remains to be clarified.
Aspirin for all? Not so fast…
Source: Ogawa H, et al. Low dose aspirin for primary prevention of atherosclerotic events in patients with Type 2 diabetes. JAMA 2008;300:2134-2141.
The syllogistic process that led us all to accept the utility of ASA in prevention of CVD in diabetics seemed innocent enough: a) ASA reduces CV events in persons with CVD, and b) Diabetes is considered a CV risk equivalent; therefore, c) ASA must reduce CV events in persons with diabetes.
Despite the quite consistent advocacy for ASA to reduce CV events in persons without known CVD (i.e., primary prevention), such primary prevention has never been shown to reduce mortality. And while adult diabetics older than age 40 have similar or even greater risk of sustaining a myocardial infarction than a non-diabetic who has already had an MI, the mechanisms inducing MI might be different in diabetics than non-diabetics; we cannot assume that just because aspirin benefits one population, it will indeed benefit another population whose background risk factors differ (for instance, diabetics typically have smaller, more dense, more atherogenic LDL than non-diabetics).
Ogawa et al published a multicenter prospective randomized trial of ASA (81-100 mg/d) vs placebo in adult, Japanese Type 2 diabetics (n = 2539). None of the subjects had sustained a known CV event, and all were free of clinically manifest PAD at baseline. The primary endpoint of the trial was a composite of fatal and nonfatal CVD events, ACS, new angina, and TIA.
After a follow-up of 4.37 years (median), although there was a trend towards reduced atherosclerotic events in the ASA group, the results were not statistically significant. The conclusion of the authors: "…low-dose ASA as primary prevention did not reduce the risk of CV events."
Non-fasting triglycerides and risk of stroke
Source: Freiberg JJ, et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008;300:2142-2152.
The consistent and strong relationship between LDL and adverse CV events, coupled with widely replicated risk reduction achieved with statins, leaves little doubt about the risk-benefit ratio of such intervention. On the other hand, both the relationship between triglycerides (TRGs) and CV events, and the benefits of lowering elevated TRGs are much less well established.
The Copenhagen City Heart Study has been following approximately 14,000 men and women since 1976. Although TRGs are typically measured fasting, the authors of this paper measured non-fasting TRG (nf-TRG) to gain insight into CV risk associated.
An analysis was performed comparing 6 incremental levels of nf-TRG. The reference level was nf-TRG < 89 mg/dL. Risk for stroke was assessed for men and women, at increments of 89 mg/dL, from an nf-TRG level of 89 mg/dL to > 443 mg/dL. For both men and women, ischemic stroke increased with increasing levels of nf-TRG. For instance, individuals with nf-TRG > 443 mg/dL had a hazard ratio 2.5-3.8 times greater than persons with nf-TRG < 89 mg/dL.
These intriguing findings suggest that nf-TRG might be useful, in concert with LDL, as a target for CV risk reduction. Of course, whether intervention to modulate nf-TRG is appropriate will depend on future interventional trials documenting that reduction of nf-TRG is beneficial.
ACE/CCB or ACE/HCTZ for HTN: Which is better?
Source: Jamerson K, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high risk patients. N Engl J Med 2008;359:2417-2428.
Jnc 7 is probably the consensus document most utilized by U.S. clinicians to make decisions about HTN. The ALLHAT trial was instrumental in establishing the equal efficacy of chlorthalidone, amlodipine, and lisinopril in reference to mortality, with some subgroups (CHF, stroke) showing superiority of chlorthalidone. These results led to the suggestion that diuretic therapy be a foundation of HTN treatment.
Clinical trials have consistently demonstrated that only a minority of patients are able to have their HTN controlled on monotherapy, and little direction has been available to guide therapy about which combination of agents provides best outcomes. The ACCOMPLISH trial was designed to compare outcomes in HTN patients (n = 11,506) considered to be high-risk because of substantial comorbidity (e.g., PAD, LVH, MI, stroke, CKD). The two regimens compared were ACE/CCB (benazepril/amlodipine) and ACE/HCTZ (benazepril/hydrochlorothiazide). The primary endpoint was a composite of CV death, nonfatal MI/stroke, hospitalization for angina, sudden death resuscitation, and revascularization.
The trial was stopped early at 36 months when the clear advantage of ACE/CCB was seen: a 20% relative risk reduction for the primary endpoint. In situations where clinicians are choosing combination therapy, ACE/CCB has been superior to ACE/HCTZ. Because HCTZ and chlorthalidone are not identical, there is some controversy over whether results would have been the same had chlorthalidone (the agent used in ALLHAT) been used instead. At the current time, since the vast majority of prescriptions for an antihypertensive diuretic in the United States employ HCTZ, these results should be generalizable to most practice situations.
Putting sunscreen to the test
Source: Sang SQ, et al. In vitro assessments of UVA protection by popular sunscreens available in the United States. J Am Acad Dermatol 2008;59:934-942.
Spf stands for "sun protection factor," but if FDA recommendations change, the name will soon stand for "Sunburn Protection Factor" because of the recognition that current SPF testing reflects erythema effects of UVA light in the 320-340 nm and UVB light in the 290-320 nm wavelengths, but does not necessarily reflect efficacy for other photodamaging wavelengths. UVA light in the 340-400 nm range is also dermotoxic, but impact of sunscreen on this light component has not previously been included in labeling. In August 2007, the FDA suggested a new rating scale which includes a ratio of UVA 340-400 nm (termed UVA1) to total UV light absorption. Agents that have low efficacy for absorbing UVA1, even though they have good efficacy for other wavelengths, would be rated lower in overall efficacy.
An analysis of 13 OTC sunscreen products using the new FDA criteria found 8 to provide medium protection and 5 to provide high protection. All but one of the selected products had an SPF of at least 30. If the proposed FDA metric becomes widely accepted, consumers will have an opportunity to better appraise the overall efficacy of sunscreen products.
White coat hypertension and Type 2 diabetes; Vitamin K and insulin resistance; Aspirin for all? Not so fast; Non-fasting triglycerides and risk of stroke; ACE/CCB or ACE/HCTZ for HTN: Which is better?; Putting sunscreen to the testYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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