Martino Laurenzi

Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction

BACKGROUND Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting beta(2)-receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited. OBJECTIVE We sought to compare montelukast and salmeterol in the long-term treatment of EIB. METHODS One hundred ninety-seven patients with mild asthma and a postexercise fall in FEV(1) of at least 18% were randomized (double-blind) to receive montelukast 10 mg once daily or salmeterol 50 microg twice daily for 8 weeks. Exercise challenge was repeated at day 3, week 4, and week 8 after randomization near the end of the dosing interval for both drugs. The primary efficacy endpoint was the maximal percent fall in postexercise FEV(1) at week 8. RESULTS Montelukast was effective in treating EIB without inducing tolerance and provided superior (P </=.001) protection than salmeterol at weeks 4 and 8, with comparable protection at day 3. The frequency of respiratory clinical adverse events (P =.046) and discontinuations because of clinical adverse events (P =.052) were less with montelukast. CONCLUSION The effect of montelukast was greater than that of salmeterol in the chronic treatment of EIB over a period of 8 weeks in patients with mild asthma as demonstrated by effect size, maintenance of effect, and fewer respiratory clinical adverse events during the study period. Montelukast may be a better alternative to salmeterol as a controller agent for the chronic treatment of EIB.

Hematocrit, Blood Pressure, and Hypertension The Gubbio Population Study

Baseline data from the Gubbio Population Study in north central Italy were used to investigate the relation of hematocrit to blood pressure and hypertension among 2,809 men and women aged 25-74 years. Independent of gender, age, and other confounders, the hypertensive group had a higher hematocrit than the nonhypertensive group (p less than 0.001). In comparison with the untreated hypertensive group, the hypertensive group being treated with diuretics or with other drugs only had similar mean hematocrit levels despite significantly lower blood pressures. Hematocrit was positively correlated with systolic pressure (r = 0.085, p less than 0.01 and r = 0.264, p less than 0.001 for men and women, respectively) and diastolic pressure (r = 0.214, p less than 0.001 and r = 0.266, p less than 0.001). In both sexes, whether or not the treated hypertensive group was included, age-adjusted prevalence of hypertension and average blood pressure were higher for persons in higher quintiles of hematocrit (p less than 0.001). The association of hematocrit with blood pressure and hypertension was significant and independent of several confounders. The regression coefficient of blood pressure on hematocrit ranged between 0.410 and 0.620 mm Hg per unit of hematocrit for systolic pressure and between 0.371 and 0.581 for diastolic pressure, depending on gender and whether the treated hypertensive group was included in multiple regression analysis. Based on exponentiation of the multiple logistic coefficient, prevalence of hypertension was at least two times greater for persons whose hematocrit levels were higher by 10 units.

Definition of Kidney Dysfunction as a Cardiovascular Risk Factor Use of Urinary Albumin Excretion and Estimated Glomerular Filtration Rate

BACKGROUND Urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) have been used separately to provide information about cardiovascular risk. We analyzed whether UAE and eGFR used together provide complementary information. METHODS We analyzed UAE, eGFR, cardiovascular risk factors, and incidence of cardiovascular disease in 1665 men and women of the Gubbio Population Study (aged 45-64 years). We designated UAE in the highest decile as high (>or= 18.6 microg/min in men and >or= 15.7 microg/min in women) and eGFR in the lowest decile as low (<64.20 mL/min/1.73 m(2) in men and <57.90 mL/min/1.73 m(2) in women). RESULTS Kidney dysfunction defined using both markers was more frequent than using 1 marker (UAE alone or eGFR alone) (P< .001) because high UAE and low eGFR clustered in different individuals and were weakly associated with each other (P= .12). The hazard ratio (HR) for incident cardiovascular disease was elevated for both markers, independently of each other (HR for high UAE, 2.15; 95% confidence interval [CI], 1.33-3.49; HR for low eGFR, 2.14; 95% CI, 1.32-3.48). Kidney dysfunction defined by both markers predicted cardiovascular disease independently of sex, age, hypertension, hypercholesterolemia, smoking, diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity (HR, 1.50; 95% CI, 1.05-2.14). The discriminant power of dysfunction defined by both markers was statistically significant (area under the receiver operating characteristic curve, 0.569 [P= .02]) and slightly higher than what was found with 1 marker of diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity. CONCLUSIONS High UAE and low eGFR provide complementary information in defining kidney dysfunction because they cluster in different individuals. Concomitant evaluation of both markers should be considered to adequately assess kidney dysfunction and cardiovascular risk.

Sodium-lithium countertransport and blood pressure: the Gubbio Population Study.

The relation of red blood cell sodium-stimulated lithium countertransport to blood pressure (BP) and prevalence of hypertension was assessed in univariate and multivariate analyses for 2,748 men and women aged 25–74 years who participated in the baseline examination of the Gubbio Population Study in north central Italy. Since age-specific countertransport values were consistently higher for men than women, all analyses were done for men and women separately. In simple correlation analyses, countertransport was significantly related to systolic and diastolk BP in both sexes (r values 0.107–0.163). In age-adjusted analyses, countertransport was significantly related to BP level of both men and women not receiving antihypertensive treatment; mean levels were high for hypertensive persons receiving antihypertensive therapy compared with normotensive persons. Age-adjusted prevalence rates of hypertension were progressively higher for both sexes in successively higher quintiles of countertransport, almost twice as high for those in the highest quintile compared with those in the lowest quintile. Correspondingly, age-adjusted logistic regression analyses showed countertransport to be related significantly to prevalence of hypertension for both men and women (p < 0.001). Since age, body mass index, plasma total cholesterol, uric acid, glucose, urinary sodium/potassium excretion, pulse, and (for men) daily alcohol intake also were significantly correlated with BP, and in some instances with countertransport, relation of countertransport to BP was also assessed in multivariate analyses with control for these variables. For men and women, multiple logistic coefficients for the relation of countertransport to prevalence of hypertension were significant (p < 0.05) or borderline significant (0.05<p < 0.10); a person with a high countertransport value was 1.3–1.9 times more likely to be hypertensive than a person with a low value. These findings indicate that the cross-sectional relation between countertransport and hypertension generally remains significant with control for other traits known to be related to hypertension. However, prospective data are lacking as to whether countertransport is an independent risk factor for incidence of hypertension. Such data are needed for further clarification of the relation of high countertransport to the etiology of hypertension.

Multiple risk factors in hypertension : results from the Gubbio study

The association between hypertension and a number of cardiovascular disease risk factors was assessed in the large population sample of Gubbio, a town in central Italy that dates back to medieval times. The data confirm those of previous studies showing that hypertension is strongly associated with other metabolic abnormalities, such as markedly overweight subjects, hyperuricaemia, hyperglycaemia, hypercholesterolaemia, that may be related to the aetiopathogenesis of high blood pressure and, in addition, compound the risk of major clinical cardiovascular events in people with hypertension. The findings are therefore relevant for prevention strategies. In addition, the association between erythrocyte sodium-stimulated lithium countertransport and hypertension is being studied

Elevated blood pressure and positive history of kidney stones: results from a population-based study

Mild hypercalciuria has been observed in hypertension, but it is not yet established whether the prevalence of urinary stone disease is increased as well. Data from the cross-sectional phase of the Gubbio Study — a population-based survey on hypertension involving 5376 subjects (84% response rate) — have been analysed to address this issue, defining as hypertensive those subjects with diastolic pressure falling within the fifth quintile for each sex- and age-specific category, and/or under regular antihypertensive treatment. The prevalence of a positive history for urinary stone (radiographic and/or surgical evidence, and/or stone excretion) was increased by over 50% (P > 0.01) in treated and untreated hypertensives. None of the 136 subjects with a positive urinary stone history were hypercalcaemic and none had renal failure.

Low Muscular Mass and Overestimation of Microalbuminuria by Urinary Albumin/Creatinine Ratio

Microalbuminuria is a mild urinary albumin elevation and is associated with cardiovascular disease. Urinary albumin/creatinine ratio is recommended for microalbuminuria assessment, because it reflects urinary albumin excretion. Muscular mass could affect albumin/creatinine ratio, because urinary creatinine reflects muscular mass. The study investigated high albumin/creatinine ratio attributed to low urinary creatinine without microalbuminuria. The Gubbio Population Study for ages 45 to 64 collected data on weight, skinfold, urinary albumin, urinary creatinine, and coronary heart disease. Weight and skinfold thickness were used to calculate fat and nonfat mass and urinary creatinine as a marker of muscular mass. Microalbuminuria was defined as urinary albumin of 20 to 199 &mgr;g/min and high albumin/creatinine ratio as a ratio of 17 to 250 &mgr;g/mg in men and of 25 to 355 &mgr;g/mg in women. Persons with macroalbuminuria (urinary albumin ≥200 &mgr;g/min) were excluded to focus analyses on microalbuminuria. Coronary heart disease was defined by ECG and questionnaire. The target cohort consisted of 1623 men and women, ages 45 to 64. Prevalence was 8.5% for high albumin/creatinine ratio (n=138), 4.3% for microalbuminuria (n=69), 5.2% for high albumin/creatinine ratio without microalbuminuria (n=85), and 1.0% for nonhigh albumin/creatinine ratio with microalbuminuria (n=16). High albumin/creatinine ratio without microalbuminuria was inversely associated with nonfat mass and urinary creatinine (P<0.04). Compared with persons with a nonhigh albumin/creatinine ratio, coronary heart disease was more prevalent in persons with a high albumin/creatinine ratio and microalbuminuria (18.9% and 7.1%; P=0.002), not in persons with a high albumin/creatinine ratio without microalbuminuria (8.2% and 7.1%; P=0.706). A high albumin/creatinine ratio in persons with low muscle mass indicates low urinary creatinine more often than microalbuminuria and cardiovascular disease.

Baseline Sodium-Lithium Countertransport and 6-Year Incidence of Hypertension The Gubbio Population Study

BACKGROUND Sodium-lithium countertransport (Na-Li CT) activity is high in persons with hypertension. This study investigated whether high Na-Li CT relates to development of hypertension. METHODS AND RESULTS At the baseline visit of the Gubbio Population Study, 4210 people of the 5376 surveyed were 18 to 74 years old; of these, 1599 were hypertensive (systolic pressure > or = 140 mm Hg, or diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy). Of the 2611 nonhypertensives, 302 did not have Na-Li CT measured and 580 did not participate in 6-year follow-up. This analysis, therefore, deals with data collected on 1729 men 18 to 74 years old and women 18 to 74 years old who at baseline were nonhypertensive and had Na-Li CT measurement. Compared with individuals who were nonhypertensive at baseline and follow-up, individuals with incident hypertension at follow-up (systolic pressure > or = 140 mm Hg, or diastolic pressure > or = 90 mm Hg, or on antihypertensive drug therapy) had higher baseline values of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake (P < .05). Baseline Na-Li CT was positively associated (P < .05) with development of hypertension in quartile analysis, with highest incidence of hypertension among men and women with Na-Li CT in the highest quartile (for men, > or = 376 and for women, > or = 311 mumol Li-L red blood cells-1.h-1). In univariate logistic regression, incidence of hypertension was related to baseline value of Na-Li CT, blood pressure, age, body mass index, plasma cholesterol, and alcohol intake (P < .05). In multiple logistic regression analysis, individuals with baseline Na-Li CT higher by 127 mumol (pooled SD for men and women) had 1.23 times greater risk of incident hypertension with control for sex and baseline age, body mass index, systolic pressure, and other confounders (P < .001). CONCLUSIONS Na-Li CT is a predictor of hypertension risk in adults.

Correlates of sodium-lithium countertransport. Findings from the Gubbio Epidemiological Study. The Gubbio Collaborative Study Group.

Background Numerous reports have presented evidence for a positive association between the maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes and hypertension. The nature of this association remains to be clarified. Methods and Results This report presents correlates of Na-Li CT in a population sample of 3,591 people aged 5–74 years. Males had higher mean age-specific levels of Na-Li CT than females except for the 5–14-year age stratum. In adults aged 25–74, for both men (n = 1,044) and women (n = 1,192), body mass index, plasma uric acid and glucose, alcohol consumption, and red blood cell mean corpuscular volume were positively related to countertransport in multivariate analyses; plasma high-density lipoprotein (HDL) cholesterol and plasma potas-sium were inversely related. Plasma non-HDL cholesterol was independently and directly related to Na-Li CT in women, and plasma sodium was inversely associated with Na-Li CT in men. These relations prevailed for men when persons with hypertension were excluded from the analyses and prevailed in part for women. When stepwise regression analyses were done for all men and women combined (n = 2,236), sex ceased to be significantly related to countertransport with plasma uric acid and alcohol intake in the model. In adults of either sex, no independent association was detected between Na-Li CT and age, heart rate, or the ratios of sodium to potassium or of sodium to creatinine in overnight untimed urine. Conclusions In both sexes, Na-Li CT is significantly and independently associated with a number of metabolic variables (plasma uric acid, plasma glucose, body mass index, plasma potassium, and life-style habits [e.g., alcohol intake]). Further research is needed to elucidate the meaning of the significant associations between Na-Li CT and the foregoing variables (all of them also related to blood pressure).

Comparison of oral montelukast and inhaled cromolyn with respect to preference, satisfaction, and adherence: a multicenter, randomized, open-label, crossover study in children with mild to moderate persistent asthma

Abstract Objective The aim of this study was to compare parent and child preference, satisfaction, and adherence of oral montelukast, a leukotriene receptor antagonist, with those of inhaled cromolyn. Background Parents are actively involved in the care of their young children with asthma. Parent and child preference and satisfaction are critical in maintaining adherence to asthma therapy and achieving optimal therapeutic outcomes. Methods Children aged 6 to 11 years with mild to moderate persistent asthma entered a multicenter, randomized, open-label, crossover trial. Children received montelukast (one 5-mg chewable tablet at bedtime) or cromolyn (2 mg 4 times daily via metered-dose inhaler), each for 4 weeks. A 2-week washout period separated the treatment periods. Parent and child preference for montelukast versus cromolyn and satisfaction with each treatment were assessed with 1-question preference and multiquestion satisfaction questionnaires. Adherence with study medications and beta-agonist use was assessed by means of diary cards. Results Two hundred sixty-six children entered the trial. Of 254 parents included in the analysis, 249 parents (98%) expressed a preference; of these, significantly more preferred oral montelukast over inhaled cromolyn (219 [88%] vs 30 [12%], P P P 95% of days) to montelukast therapy, whereas 122 children (48%) were adherent to cromolyn therapy ( P P = 0.001). Both therapies were generally well tolerated. Conclusions Parent and child preference, satisfaction, and adherence were all significantly better with oral montelukast compared with inhaled cromolyn. Treatment with oral montelukast may improve the outcomes of asthma therapy in children.