Antibiotic therapy after acute myocardial infarction. A prospective randomized study

Methods: 2623 subjects in the Framingham Offspring Study were evaluated by echocardiography and fasting and 2-hour FBS and insulin post 75-gram oral glucose load in non diabetics (FBS ⬍126 mg/mL). Insulin resistance was assessed from fasting glucose and insulin levels by the homeostasis model assessment [HOMA-IR ⫽ fasting glucose (mmol/L) ⫻ fasting insulin (␮U/mL)/22.5]. Echo measurements were made from m-mode echoes. Results: Mean age was 53 years, 60% were women and BMI averaged 26 kg/m2. Systolic BP, BMI and HOMA-IR increased with worsening glucose tolerance. HOMA-IR was strongly related to BMI in both the normal and abnormal glucose tolerance groups (rⱖ0.40 in both men and women). LV mass (adjusted for age, height, and systolic pressure) increased across categories of worsening glucose tolerance, and was more striking in women. In both subjects with normal and abnormal glucose tolerance, covariate adjusted LV mass and wall thickness increased across HOMA-IR quartiles in women but not men. Covariate adjusted LA size increased with worsening glucose tolerance and across HOMA-IR quartiles in both sexes. Adjustment for BMI considerably attenuated the relations of LV/LA measures and HOMA-IR, rendering them insignificant in the normal tolerance group. Conclusions: In a large community-based sample, LV mass and wall thickness increased with worsening glucose tolerance, particularly in women. Insulin resistance was associated with increase LV mass in women, which was largely accounted for by obesity. Perspective: In contrast to LV mass, the increase in LA size was related to insulin resistance in men and women, suggesting LA size may be influenced by factors independent of their impact on LV mass. An increase in LA size may be an early marker of LV diastolic impairment associated with glucose intolerance even with normal LV mass. MR

a maximum of 100 mg of losartan, 3 mg of trandolapril or a combination of both drugs at the equivalent doses. Results: The mean age was 45 years, 47% were male, mean BP 130/75 mm Hg, 65% had glomerular disease, 18% hypertension, and there was no between group difference in ACE gene polymorphism. The mean serum creatinine was 2.9 mg/mL, 22% had ⬎3 gm/day of proteinuria, 40% 1–3 gm/day and 38%% ⬍1 gm/day. Eleven percent of the 85 patients on the ARB⫹ACEi reached the combined primary end point compared to 23% on ACEi alone and 23% on the ARB, a 60% reduction with the combination compared to either monotherapy, p⫽0.02. Covariates effecting renal survival were the combined treatment, age, baseline renal function, use of diuretics (20% decreased mortality) and the reduction in proteinuria attributable to the ACEi. Side effects with the combination were the same as with the ACEi alone. On treatment, BP decreased by about 5 mm Hg systolic and 3 mm Hg diastolic and did not differ between groups. Conclusions: Combination treatment with losartan and trandolapril safely retards progression of non-diabetic renal disease compared to monotherapy. Perspective: The benefits of the combination were not always present in other smaller studies including diabetes. The value and safety of combining ACEi⫹ARB needs to be tested in larger and ethnically diverse cohorts and in other indications such as hypertension and congestive heart failure. MR

Antibiotic Therapy After Acute Myocardial Infarction. A Prospective Randomized Study Zahn R, Schneider S, Frilling B, et al. Circulation 2003;107: 1253–9. Study Question: Exposure to chlamydia pneumoniae (c. pneumoniae) appears to contribute to the pathogenesis of atherosclerosis. This study sought to determine whether the macrolide antibiotic roxithromycin reduces mortality or morbidity in patients with acute myocardial infarction. Methods: This was a multicenter (68 German hospitals) double-blind placebo-controlled trial of 300 mg roxithromycin daily for 6 weeks in 872 men and women with an AMI (non-STEMI or STEMI) with a 12-month follow-up. Treatment was begun within 5 days after admission. The primary end point was total mortality at 12 months, and combined secondary end points included 1) death, reinfarction, stroke or post-MI angina during the hospitalization; 2) same outcomes at 12 months and 3) the need for revascularization. Results: The mean age was 60 years, 79% were male, about 45% had an anterior MI and 50% were smokers. There was a lower prevalence of COPD in the roxithromycin group (.35% vs. 6.9%, p⫽0.028). Treatment was more often stopped by the patient prior to 4 weeks in the active drug group than placebo (18% vs. 11%, p⫽0.003). Total mor-

Combination Treatment of Angiotensin-II Receptor Blocker and Angiotensin-Converting-Enzyme Inhibitor in Non-Diabetic Renal Disease (COOPERATE): A Randomised Controlled Trial Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Lancet 2003;361:117–24. Study Question: To assess the safety and efficacy of combined treatment with an ACEi and ARB and monotherapy of each drug at maximum doses in non-diabetic chronic renal disease. Methods: This was a randomized double-blind trial in men and women 18 –70 years with chronic renal failure (CRF) defined as a serum creatinine of 1.45– 4.5 mg/dL or a GFR 20 –70 mL/min per 1.73m2 (normal range 90 –130 mL/min per 1.73m2). Following an 18 week run-in period, 263 of the initial 336 patients screened with non-diabetic renal disease were randomly assigned and titrated to tolerance to

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tality was about 6%. There was no difference in primary or secondary end points at hospital discharge or 12 months whether adjusted or unadjusted for differences in baseline characteristics or 4- or 6-week drug compliance. Conclusions: Treatment of AMI patients with roxithromycin did not reduce event rates during a 12-month follow-up. Perspective: This report adds to the list of negative large trials of antibiotics targeted to c. pneumoniae in CHD. This does not preclude the hypothesis that prevention and early treatment of local and systemic infections may reduce coronary events by reducing the systemic inflammatory burden and response. MR

PAD. The relative risk of history of periodontal disease for PAD was 1.41 (95% CI, 1.12–1.77) and for any tooth loss during the follow-up period was 1.39 (95% CI, 1.07–1.82), controlling for traditional risk factors of cardiovascular disease. Among men with a history of periodontal diseases, the relative risk of tooth loss increased to 1.88 (95% CI, 1.27–2.77), whereas no association was found between tooth loss and PAD among those without periodontal diseases (RR, 0.92; 95% CI, 0.61–1.38). The investigators further explored the potential induction period of tooth loss and found that tooth loss in the previous 2 to 6 years was most strongly associated with PAD. Conclusions: The investigators found that incident tooth loss was significantly associated with PAD, especially among men with periodontal diseases. Perspective: This large scale prospective registry demonstrated that men with a history of periodontal diseases or with any tooth loss during follow-up had a significantly higher risk of PAD than men without any periodontitis or without any tooth loss. There was no apparent association between number of teeth at baseline and PAD. The results support a potential oral infection/inflammation pathway for PAD. Atherosclerosis is a complex, multifactorial disease with a significant component of inflammation. Recently, infectious agents have been proposed as accelerators of atherosclerosis through nonspecific stimulation of the inflammatory cascade. Future studies, which measure serum levels of inflammatory markers, may help delineate the mechanism of the increased risk of vascular disease in individuals with periodontitis. MR

Oral Health and Peripheral Arterial Disease Hung H, Willett W, Merchant A, Rosner BA, Ascherio A, Joshipura KJ. Circulation 2003;107:1152–7. Study Question: The investigators sought to examine the association between poor oral health and peripheral arterial disease (PAD). Methods: In a prospective study of 45,136 eligible male health professionals in the Health Professionals Study among individuals who were free of cardiovascular diseases at baseline, the investigators identified 342 cases of PAD during a 12-year follow-up period. They evaluated the association between different measures of oral diseases and the occurrence of PAD. Results: Baseline number of teeth was not related to the risk of PAD, but cumulative incident tooth loss was significantly associated with elevated risk of subsequent occurrence of

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