Valentina Boyko

Peroxisome Proliferator–Activated Receptor Ligand Bezafibrate for Prevention of Type 2 Diabetes Mellitus in Patients With Coronary Artery Disease

Background—Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator–activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period. Methods and Results—The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P =0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6±2.3 versus 3.8±2.6 years (P =0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16). Conclusions—Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.

Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease

The benefit of beta-blocker therapy in patients after myocardial infarction is well established. The use of beta blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) beta blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving beta blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified beta-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with beta-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with beta blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.

Perceptual, Social, and Behavioral Factors Associated With Delays in Seeking Medical Care in Patients With Symptoms of Acute Stroke

Background and Purpose— Despite availability of reperfusion therapy for acute ischemic stroke, most patients remain ineligible mainly because of late hospital arrival. We hypothesized that perceptual, social, and behavioral factors affect delays in seeking help after symptom onset. Methods— Patients presenting with stroke symptoms were interviewed about symptom experiences, interpretations, and reactions. Odds ratios (95% CI) for risk of delay >3 hours were estimated, and variables associated with increased risk and representing demographic, clinical, perceptual, social, and behavioral factors were included in an assessment of the effect of combined risk factors on delay. Results— Among 209 patients (mean age 61.8±12 years, 69% men) the median time interval from symptom awareness to seeking help was 2 (0.5 to 9) hours and to hospital arrival, 4.2 (1.3 to 14.5) hours. On multivariate adjustment, perceiving symptoms as severe (odds ratio [OR]: 0.42; 0.17 to 0.95), advice from others to seek help (OR: 0.18; 0.05 to 0.63), and contacting an ambulance (OR: 0.26; 0.10 to 0.63) were associated with decreased risks of delay, whereas perceived control of symptoms (OR: 2.45; 1.08 to 5.71) increased risk of delay in seeking help. Risk of delay in hospital arrival was 3 times greater in women than in men. Increasing proportions of patients who delayed seeking help were observed with increasing numbers of combined risk factors, ranging from 17% to 94% for 0 to 1 and 6 to 7 factors, respectively. Conclusions— Perceptual, social, and behavioral factors contribute to delay in seeking medical care in acute ischemic stroke beyond demographic and clinical variables, and, when combined, further increase risk of delay. These findings may be important for designing programs to reduce delay.

Is there an association between hypertension and cancer mortality

BACKGROUND Because of suggestions that hypertension may increase the long-term risk of cancer, we assessed the relation between hypertension and malignancy. METHODS We conducted a MEDLINE search of English-language articles published between January 1966 and January 2000 using the terms hypertension or blood pressure, and neoplasm or cancer or malignancy. We reviewed prospective studies that reported cancer incidence or mortality in hypertensive and nonhypertensive patients, case-control studies that reported the prevalence of hypertension in cancer patients and controls, and references from identified articles. RESULTS We identified 10 longitudinal studies that evaluated the association between blood pressure and cancer mortality in 47 119 subjects. Subjects with hypertension experienced an increased rate of cancer mortality during durations of follow-up ranging 9 to 20 years, with an age- and smoking-adjusted pooled odds ratio of 1.23 (95% confidence interval [CI]: 1.11 to 1.36). In 13 case-control studies, including 6964 cases of renal cell cancer and 9181 controls, the adjusted odds ratio for renal cell cancer among hypertensive patients, relative to normotensive counterparts, was 1.75 (95% CI: 1.61 to 1.90). No clear association was found between hypertension and cancer of other sites. CONCLUSION Hypertension was associated with an increased risk of mortality from cancer, particularly renal cell carcinoma.

Prognostic significance of mild mitral regurgitation by color Doppler echocardiography in acute myocardial infarction

Mitral regurgitation (MR) complicating acute myocardial infarction (AMI) is associated with increased mortality. The prognostic significance of only mild MR detected by echocardiography in patients with AMI is unknown. This study assessed the long-term risk associated with mild MR detected by color Doppler echocardiography within the first 48 hours of admission in 417 consecutive patients with AMI. No MR was detected in 271 patients (65%), mild MR was seen in 121 patients (29%), and moderate or severe MR was noted in 25 patients (6%). One-year mortality rates were 4.8%, 12.4%, and 24%, respectively (p<0.001). Multivariate analysis revealed that mild MR was independently associated with increased 1-year mortality (p<0.05) after adjustment for age, gender, previous myocardial infarction, diabetes mellitus, systemic hypertension, Killip grade > or =2 on admission, and left ventricular ejection fraction < or =40%. The hazard ratio for 1-year mortality was 2.31 (95% confidence interval 1.03 to 5.20) for mild MR and 2.85 (95% confidence interval 0.95 to 8.51) for moderate or severe MR. Thus, mild MR detected by color Doppler echocardiography within the first 2 days of admission in patients with AMI is a significant independent risk predictor for 1-year all-cause mortality.

Effect of gender on outcomes of acute coronary syndromes.

can be a valuable tool for the management of patients who undergo diagnostic and interventional angiographic procedures. The effectiveness of the QuickSeal was demonstrated by a significant decrease in TTH and TTA in diagnostic and interventional patients. This led to a significant decrease in time to eligibility for hospital discharge and time to discharge. Importantly, this benefit was not accompanied by any increase in major complications in the QuickSeal group. There were no reported incidents of infection or adverse tissue reactions in any of the QuickSealtreated patients. The extravascular delivery of Gelfoam makes the device safe for use in patients with common femoral artery disease and in patients where the puncture site may involve the common femoral artery bifurcation. The extravascular nature of the device eliminates the need for a femoral angiogram at the end of the procedure. The device received Food and Drug Administration approval in March 2002.

Prospective Study of Serum Homocysteine and Risk of Ischemic Stroke Among Patients With Preexisting Coronary Heart Disease

Background and Purpose— Substantial evidence is accumulating suggesting that hyperhomocysteinemia may be a risk factor for ischemic stroke. Results of prospective studies are, however, conflicting, and the role of hyperhomocysteinemia in patients with preexisting atherosclerotic vascular disease is not clear. Our aim was to assess prospectively the risk of incident ischemic stroke conferred by serum total homocysteine among patients with preexisting stable coronary heart disease (CHD). Methods— We obtained baseline fasting serum samples from patients with chronic CHD enrolled in the Bezafibrate Infarction Prevention (n=3090) secondary prevention study cohort. With a nested case-control design, we measured baseline total homocysteine concentration by a high-performance liquid chromatography–based method in sera (n=160) of matched case-control pairs: patients who developed ischemic stroke during a mean follow-up of 8.2 years (cases) and age- and sex-matched controls without subsequent cardiovascular events. Results— An increase of 1 natural log unit in homocysteine concentration was associated with a >3-fold increase in relative odds of incident ischemic stroke (3.3; 95% CI, 1.2 to 10.2). Homocysteine concentrations at the highest quartile (>17.4 &mgr;mol/L) were associated with significantly higher odds of ischemic stroke compared with the lowest quartile in matched-pair analysis (3.1; 95% CI, 1.1 to 9.8) and after multivariable adjustments (4.6; 95% CI, 1.3 to 18.9). Adding fibrinogen or soluble intercellular adhesion molecule-1 concentrations, markers of inflammation, to the model did not attenuate this association. The linear trends across the quartiles were significant for all models (P <0.05). Conclusions— Serum total homocysteine concentration is a strong predictor for incident ischemic stroke among patients at increased risk because of chronic CHD. The graded association observed is independent of traditional risk factors or inflammatory markers and indicates the importance of serum homocysteine levels in patients with preexisting vascular disease.

THE PREDICTIVE VALUE OF ADMISSION HEART RATE ON MORTALITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

The purpose of this study was to assess the predictive value of admission heart rate (HR) for in-hospital and 1 year post-discharge mortality in a large cohort of patients hospitalized for acute myocardial infarction (MI). Data were derived from the SPRINT-2 secondary prevention study population, and included 1044 patients (aged 50-79), hospitalized in 14 coronary care units in Israel with acute MI in the years 1985-1986, before the beginning of thrombolytic therapy in acute MI. Demographic, historical and medical data were collected for each patient. All deaths during initial hospitalization and 1 year post-discharge were recorded. In-hospital mortality was 5.2% for 294 patients with HR < 70 beats/min, 9.5% for 532 patients with HR 70-89 beats/min, and 15.1% for 323 patients with HR > or = 90 beats/min (p < 0.01). One year post-discharge mortality was 4.3% for patients with HR < 70 beats/min, 8.7% for patients with HR 70-80 beats/min and 11.8% for patients with HR > or = 90 beats/min (p < 0.01). An increasing trend of mortality with higher HR was confined to patients with mild CHF (p = 0.02) and likely to patients with absent CHF (p = 0.06), but this post hoc observation requires confirmation in larger groups. The combination of high admission HR (> or = 90 beats/min) and a systolic blood pressure < 120 mmHg was a powerful predictor of in-hospital mortality. Multivariate analysis showed that admission HR was an independent risk factor for in-hospital and 1 year post-discharge mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble intercellular adhesion molecule-1 and long-term risk of acute coronary events in patients with chronic coronary heart disease. Data from the Bezafibrate Infarction Prevention (BIP) Study.

OBJECTIVES The goal of this study was to assess soluble intercellular adhesion molecule-1 (sICAM-1) level as a predictor of future acute coronary events in patients with chronic coronary heart disease (CHD). BACKGROUND Increased sICAM-1 concentration has been shown to be associated with the incidence of CHD in healthy persons. Its significance in patients with CHD has been scarcely investigated. METHODS We designed a prospective, nested case-control study. Sera were collected from patients with CHD enrolled in a secondary prevention trial that evaluated the efficacy of bezafibrate in reducing coronary events. We measured baseline sICAM-1 concentration in the sera of patients who developed subsequent cardiovascular events (cases: n = 136) during follow-up (mean: 6.2 years) and in age- and gender-matched controls (without events: n = 136). RESULTS Baseline serum concentrations of sICAM-1 were significantly higher in cases versus controls (375 vs. 350 ng/ml; p < 0.05). Each 100 ng/ml increase in sICAM-1 concentration was associated with 1.27 (95% confidence interval [CI]: 1.00 to 1.63) higher relative odds of coronary events. Soluble ICAM-1 concentration in the highest quartile (>394 ng/ml) was associated with significantly higher odds of coronary events (compared with the lowest quartile), even after multivariate adjustment (2.31, 95% CI: 1.02 to 5.50). After adding fibrinogen and total white blood cell count to the multivariate model, the relative odds were 2.12 (95% CI: 0.88 to 5.35) and 2.70 (95% CI: 1.10 to 7.05), respectively. CONCLUSIONS Elevated sICAM-1 concentration in CHD patients is associated with increased risk of future coronary events independent of other traditional risk factors.

Ten-year survival after acute myocardial infarction: Comparison of patients with and without diabetes

Abstract In a prospective study among 5839 consecutive patients after acute myocardial infarction (AMI), the prognosis of men and women with diabetes was compared with that of patients without diabetes after AMI. The prevalence of insulin-treated diabetes or diabetes treated with oral hypoglycemic drugs was 2% and 8% among men and 6% and 12% among women respectively. After multiple regression analysis, the odds ratio for in-hospital mortality was 1.26 (95% confidence interval [CI] 0.82 to 1.92) for non-insulin-treated men with diabetes and 2.24 (95% CI 1.14 to 4.38) for those treated with insulin. Among women, these odds ratios were 1.46 (95% CI 0.90 to 2.36) and 1.80 (0.93 to 3.51), respectively. The 10-year relative risk for death was 1.32 (95% CI 1.10 to 1.58) for men with non-insulin-treated diabetes and 1.75 (95% CI 1.26 to 2.45) for men treated with insulin. For women, the respective relative risks for 10-year mortality were 1.41 (95% CI 1.10 to 1.82) for those treated with oral hypoglycemic drugs and 2.59 (95% CI 1.89 to 3.56) for diabetic women treated with insulin. We conclude that (1) diabetes requiring treatment emerged as an independent predictor of short- and long-term mortality after AMI; (2) diabetic women had a worse long-term prognosis than diabetic men after AMI; and (3) diabetic patients treated with insulin had the worst short- and long-term prognosis after AMI in both genders. (Am Heart J 1997;133:290-6.)