S.D. Hobbs

LDL Cholesterol is Associated with Small Abdominal Aortic Aneurysms

OBJECTIVE To examine the relationship between serum lipids and abdominal aortic aneurysms (AAA). METHODS Two hundred and six males (>50 years) with AAA (> or =30 mm) detected in a population based screening programme were compared with 252 age-matched male controls in a nested case-control study. Smoking status, previous medical and family histories, height, weight, blood pressure, ankle brachial pressure index (ABPI) and non-fasting lipid profile were recorded. RESULTS Cases were found to have significantly higher LDL cholesterol than controls. LDL cholesterol was an independent predictor of the risk for aneurysms in a logistic regression model adjusting for smoking status, family history of AAA, history of ischaemic heart disease, presence of peripheral vascular disease, use of lipid lowering medication and treatment for hypertension. There was a linear effect with increased levels of LDL cholesterol increasing the risk of having a small aneurysm (test for trend p=0.03). CONCLUSION The highly significant association between LDL cholesterol and small aneurysms suggests that LDL, possibly acting via inflammatory mediated matrix degeneration, could be an initiating factor in the development of AAA. The ability of statin therapy to prevent AAA formation requires further investigation.

The prevalence of hyperhomocysteinemia, methylene tetrahydrofolate reductase C677T mutation, and vitamin B12 and folate deficiency in patients with chronic venous insufficiency

INTRODUCTION Hyperhomocysteinemia (HHcy) is a risk factor for venous thromboembolism, which in turn is a major cause of chronic venous insufficiency. HHcy may be more common in patients with chronic venous insufficiency, but the cause is unknown. METHODS One hundred hospital outpatients (52 women; median age, 66.5 years [interquartile range, 53-77 years] with venous disease C(2-6) underwent assessment of serum vitamin B(12) and folate concentration, plasma Hcy concentration, and C677T methylene tetrahydrofolate reductase (MTHR) homozygosity with polymerase chain reaction. HHcy was defined as greater than 15 micromol/L, the 95th centile of the normal range. RESULTS CEAP classification was C(2) in 39 patients, C(3) in 10 patients, C(4) in 13 patients, C(5) in 15 patients, and C(6) in 23 patients, with median Hcy concentration 11.6, 11.5, 12.5, 15.1, and 18.1 micromol/L, respectively (Kruskall-Wallis test, P <.001). Overall prevalence of HHcy was 39% (P <.001, binomial test vs normal population), and was significantly related (Pearson chi(2) for trend, 13.616; P <.009) to clinical grade: C(2), 23%; C(3), 20%; C(4), 39%; C(5), 53%; C(6), 65%. In a linear regression model, C(6) disease was a strong independent predictor (R(2) = 20.1%) for Hcy. Overall, 5 of 49 patients (10%, NS compared with normal population [5%]) with C(2-3) disease and 10 of 51 patients (20%) (P <.001, binomial test) with C(4-6) disease were homozygous for the C677T MTHFR polymorphism. Hcy levels and prevalence of HHcy were negatively correlated with vitamin B(12) levels (r = -0.248, P =.021, and r = -0.225;, P =.037, respectively). There was no significant relationship with folate. HHcy was present in 3 patients (all with C(5-6) disease) with either vitamin B(12) or folate deficiency, and in 8 of 15 patients homozygous for MTHFR C677T. No patient had HHcy, vitamin deficiency, and C677T mutation. CONCLUSION HHcy is common in patients with chronic venous insufficiency, especially those with ulceration. However, inasmuch as fewer than a third of patients with HHcy were C677T MTHFR homozygous or had vitamin B(12) or folate deficiency, other mechanisms must be responsible in the majority. Further work is required to determine the cause of HHcy in chronic venous insufficiency, whether HHcy is causally related to development and progression of the disease, and whether treatment would be beneficial.

Effect of ramipril on renal function in patients with intermittent claudication

Background The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in patients with peripheral arterial disease (PAD). Despite this, general practitioners and vascular surgeons remain reluctant to prescribe ACE inhibitors in this group of patients because of concerns about renal artery stenosis (RAS). We aimed to define the effect of ramipril on renal function in patients with intermittent claudication (IC). Methods and Results Of 132 unselected patients with IC entering the study 78 (59%) were excluded due to: current ACE inhibitor use (38%), renal impairment (serum creatinine above normal range) (15%), known severe RAS (1%) or unwillingness to participate (5%). The remaining 54 patients were titrated to 10 mg ramipril and renal function was monitored at 1, 5, and 12 weeks. Treatment was discontinued during titration in 5 patients due to symptoms (3) or lack of compliance (2). In the remainder, median [IQR] serum creatinine increased (94 [85.8–103.3] to 98 [88.0–106.5] μmol/L, p ≤ 0.001) and median [IQR] GFR decreased (71.5 [64.6–82.3] to 68.7 [59.8–74.7] mL/min per 1.73 m2, p ≤ 0.001) between baseline and 5 weeks. These changes were not considered clinically significant. By 12 weeks these values had returned almost to baseline (Cr 95.5 [88.0–103.25] μmol/L, GFR 71.8 [65.3–77.4] mL/min). No patient had a serum creatinine rise >30%. Conclusion Most of patients with IC and a normal serum creatinine can be safely commenced on ramipril provided they are screened, titrated and monitored as described above. Studies in patients with borderline renal impairment (serum creatinine up to 30% above baseline) are on-going.