Donald R. Smith

Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions Two Years’ Follow-Up by High-Resolution Noninvasive Magnetic Resonance Imaging

Background—Statins are widely used to treat hypercholesterolemia and atherosclerotic disease. Noninvasive MRI allows serial monitoring of atherosclerotic plaque size changes. Our aim was to investigate the effects of lipid lowering with simvastatin on atherosclerotic lesions. Methods and Results—A total of 44 aortic and 32 carotid artery plaques were detected in 21 asymptomatic hypercholesterolemic patients at baseline. The effects of statin on these atherosclerotic lesions were evaluated as changes versus baseline in lumen area (LA), vessel wall thickness (VWT), and vessel wall area (VWA) by MRI. Maximal reduction of plasma total and LDL cholesterol by simvastatin (23% and 38% respectively;P <0.01 versus baseline) was achieved after ≈6 weeks of therapy and maintained thereafter throughout the study. Significant (P <0.01) reductions in maximal VWT and VWA at 12 months (10% and 11% for aortic and 8% and 11% for carotid plaques, respectively), without changes in LA, have been reported. Further decreases in VWT and VWA ranging from 12% to 20% were observed at 18 and 24 months. A slight but significant increase (ranging from 4% to 6%) in LA was seen in both carotid and aortic lesions at these later time points. Conclusion—The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.

Hypertension Secondary to Renal Artery Occlusive Disease

Historically, the awareness of renal artery narrowing as a curable cause of hypertension has evolved gradually, highlighted especially by Goldblatt and Poutasse. The increasing use of renal arteriography over the past 8 years in this hospital has yielded a total of 70 patients with renal artery abnormalities out of 110 hypertensive patients examined. In order to select the hypertensive patients most likely to have demonstrable arterial lesions, certain indications for arteriography were used. Most useful among these were the presence of an epigastric bruit, malignant hypertension, atheroselerosis of the abdominal aorta, and recent onset of hypertension. However, no one indication was always present in patients with lesions or always absent in those without abnormalities. Of the 70 patients with renal artery abnormalities, 54 were considered to represent sufficient renal artery stenosis to be potential candidates for surgical correction, while 16 had minor renal artery abnormalities. Atherosclerotic lesions occurred in 63 per cent of the patients with significant lesions, fibromuscular hyperplasia in 28 per cent, unilateral renal artery hypoplasia or atrophy in 7 per cent, and one case had embolic renal artery occlusion. Fifty-four per cent of all patients with significant lesions had bilateral disease. The patients with atherosclerotic lesions and those with fibromuscular hyperplasia differed markedly in sex distribution, age, and severity of hypertension. It is suggested that the retrograde transfemoral catheterization technic may be associated with fewer complications in patients without extensive occlusive atherosclerotic disease of the aorta, and iliac and femoral arteries. At operation the radiologic findings were confirmed in all but one patient. Corrective surgical procedures were performed in 38 patients, including nephrectomy, endarterectomy, segmental resection with reanastomosis, and splenorenal arterial shunt. Of the 31 patients who survived, 25 (81 per cent) had a postoperative fall in blood pressure, 14 to normal, in addition to improvement in clinical status. The follow-up period, however, is not yet sufficiently long to permit definite conclusions. Seven patients died; most of these had bilateral renal artery disease and extensive atherosclerosis of the cerebral and coronary arteries. Divided renal function studies were of limited diagnostic value because of the high incidence of bilateral lesions. In all patients with significant differences in renal sodium and water excretion, a postoperative fall in blood pressure occurred, but the same number of patients with equal bilateral excretion also had a fall in blood pressure. The importance of suspecting renal artery lesions in hypertensive patients regardless of age, severity of hypertension, or renal function is stressed. The question is discussed whether all patients with sustained hypertension should undergo arteriography. Although further studies to determine the true prevalence of occlusive renal artery lesions in the hypertensive population are in order, the fact that 50 per cent of our 110 patients had occlusive lesions and 60 per cent of the operated cases had a fall in blood pressure attests not only to the prevalence of the lesion but also to its potential curability.

Radiculitis Distress as a Mimic of Renal Pain

It is the experience of the urological author that radiculitis secondary to costovertebral joint derangement is the most common cause of lower abdominal pain. However, this pain is sometimes made worse when the patient is subjected to a flank incision for presumed renal disease, since the aftermath of a flank incision may be a downward pull on a rib owing to detachments of muscles attached to its superior surface. Emotional problems, too, befall many patients with radiculitis-despondency over delayed diagnoses or sensitivity at having been told their complaints are psychosomatic. Most often theses difficulties disappear spontaneously once the pain is relived. Definitive diagnosis requires orthopedic techniques. Unfortunately, few orthopedists are well versed or interested in the syndrome of renal pain. When they are, erroneous diagnosis can be corrected and a course of conservative or surgical treatment prescribed, with excellent results.

Antithrombotic potency of ticagrelor versus clopidogrel in type-2 diabetic patients with cardiovascular disease

Type-2 Diabetes Mellitus [T2DM] is associated with increased platelet reactivity and hypo-response to antiplatelet drugs. Ticagrelor, with its faster and more potent antiplatelet effects, was shown to reduce adverse events more than clopidogrel in the overall CAD patient population of PLATO trial, but the benefits did not reach statistical significance in the T2DM subgroup. To better understand these findings, we compared the antithrombotic effects of ticagrelor versus with clopidogrel in T2DM patients with cardiovascular disease. In a randomized, 2 treatment-sequence, crossover-design, T2DM patients (n=20, 57±8 years, 60 % male) received a loading-dose [LD] plus one week of daily-therapy [DT] of clopidogrel or ticagrelor. Treatment effects were assessed by measuring thrombus formation (Badimon Chamber) and platelet aggregation (Multiple Electrode Aggregometry (MEA) Analyzer and VerifyNow®) at 2- and 6-hour post-LD and on Day-7 of DT, in comparison with pre-treatment baseline. After 2 weeks of washout, patients switched to the second treatment under identical testing conditions. Ticagrelor significantly reduced thrombus formation versus baseline at 2- and 6-hour post-LD and Day-7 of DT (33 %, 40 % and 31 %, respectively, p<0.01 for all) whereas thrombus reductions with clopidogrel were much lower and significant only at 6-hour post-LD (16 %, 20 % and 17 %, respectively). Antithrombotic effect of ticagrelor at 6-hour was significantly stronger than clopidogrel (p<0.05). Platelet aggregation (MEA and VerifyNow®) was inhibited by both treatments but effects of ticagrelor were significantly stronger at each time-point. Ticagrelor exhibits a faster and more potent antithrombotic effect than clopidogrel in T2DM patients with cardiovascular disease, supporting its use in this population.