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A study was conducted to investigate and identify genetic variants that are associated with cardiac structure and function through a meta-analysis. Results indicated that there were 5 genetic loci, associated with variance in cardiac dimensions and aortic root size; however, the proportion of variance is quite small.

The risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users and nonusers are compared. The results revealed that conjugated equine estrogen associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.

The relationship between the use of antibiotics and the risk of breast cancer was studied. The study reveals that the use of antibiotics is associated with increased risk of incident and fatal breast cancer.

People with a mutation in the gene for a protein called alpha adducin may benefit from treatment with diuretics to prevent a heart attack or stroke, according to a study of 1,038 people. This mutation causes salt-sensitive hypertension., Context A genetic variant in [alpha]-adducin has been associated with renal sodium reabsorption and salt-sensitive hypertension. Whether this genetic variant modifies the effect of diuretic therapy on the incidence of myocardial infarction (MI) and stroke is unknown. Objectives To estimate the interaction between [alpha]-adducin and diuretic therapy on the risk of MI or stroke. Specifically, we hypothesized that in participants with treated hypertension, the risk of MI or stroke associated with diuretic use would be lower in carriers of the adducin variant than in carriers of the adducin wild-type genotype. Design, Setting, and Participants Population-based case-control study of patients enrolled in a health maintenance organization, treated pharmacologically for hypertension, and genotyped as homozygous carriers of the adducin wild-type genotype or carriers of i or 2 copies of the Trp460 variant allele. Cases had a first nonfatal MI (n=206) or stroke (n=117) between January 1995 and December 1998. Controls (n=715) were a stratified random sample of pharmacologically treated hypertensive patients who were matched to MI cases by age, sex, and calendar year. Main Outcome Measure Risk of the combined outcome of first nonfatal MI or stroke. Results The adducin variant was present in more than one third of the participants. Among the 653 carriers of the adducin wild-type genotype, diuretic therapy was not associated with the risk of Ml or stroke (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.78-1.52). Among the 385 carriers of the adducin variant allele, diuretic therapy was associated with a lower risk of the combined outcome of Ml and stroke than other antihypertensive therapies (OR, 0.49; 95% CI, 0.32-0.77). The OR in carriers of the adducin variant was less than half of the OR in carriers of the wild-type genotype (P=.005). The case-control synergy index (SI) was 0.45 (95% CI, 0.26-0.79) for the combined outcome of MI and stroke. The point estimates of the diuretic-adducin interaction were similar in separate analyses of MI (SI, 0.41; 95% CI, 0.21-0.80) and stroke (SI, 0.53; 95% CI, 0.24-1.19). The diuretic-adducin interaction was not confounded by traditional cardiovascular risk factors, was specific to diuretic therapy but not pres ent for other major antihypertensive drug classes, and did not differ substantially between subgroups defined by age, sex, race, diabetes, and history of cardiovascular disease. Conclusions In carriers of the adducin variant, diuretic therapy was associated with a lower risk of combined Ml or stroke than other antihypertensive therapies. If these findings are confirmed in other studies, this large subgroup of the hypertensive population may be especially likely to benefit from low-dose diuretic therapy.

Diuretics and beta blockers remain the treatment of choice for hypertension. Researchers reviewed all of the long-term clinical trials of antihypertensive drugs, including beta blockers, diuretics, ACE inhibitors and calcium channel blockers. There is strong evidence that diuretics and beta blockers can reduce the risk of stroke and heart failure, which are the major complications of chronic hypertension. There is much less evidence that ACE inhibitors and calcium channel blockers are effective, except in speciific patient groups such as those with coronary artery disease and congestive heart failure., Objective.--To review the scientific evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major disease end points. Data Sources.--MEDLINE searches and previous meta-analyses for 1980 to 1995. Data Selection.--We selected long-term studies that assessed major disease end points as an outcome. For the meta-analysis, we chose placebo-controlled randomized trials. For randomized trials using surrogate end points such as blood pressure, we selected the largest studies that evaluated multiple drugs. Where clinical trial evidence was lacking, we relied on information from observational studies. Data Synthesis.--Diuretics and [Beta]-blockers have been evaluated in 18 long-term randomized trials. Compared with placebo, [Beta]-blocker therapy was effective in preventing stroke (relative risk [RR], 0.71; 95% confidence interval [CI], 0.59-0.86) and congestive heart failure (RR, 0.58; 95% CI, 0.40-0.84). The findings were similar for high-dose diuretic therapy (for stroke, RR, 0.49; 95% CI, 0.39-0.62; and for congestive heart failure, RR, 0.17; 95% CI, 0.07-0.41). Low-dose diuretic therapy prevented not only stroke (RR, 0.66; 95% CI, 0.55-0.78) and congestive heart failure (RR, 0.58; 95% CI, 0.44-0.76) but also coronary disease (RR, 0.72; 95% CI, 0.61-0.85) and total mortality (RR, 0.90; 95% CI, 0.81-0.99). Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure in hypertensive patients, the clinical trial evidence in terms of health outcomes is meager. For several short-acting dihydropyridine calcium channel blockers, the available evidence suggests the possibility of harm. Whether the long-acting formulations and the nondihydropyridine calcium channel blockers are safe and prevent major cardiovascular events in patients with hypertension remains untested and therefore unknown. Conclusion.--Until the results of large long-term clinical trials evaluating the effects of calcium channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and [Beta]-blockers as first-line agents and low-dose therapy for all antihypertensive agents. JAMA. 1997;277:789-745

People taking calcium channel blockers appear to have a greater risk of heart attack than those taking other classes of drugs used to lower blood pressure. Researchers studied the records of 623 patients who had heart attacks while taking antihypertensive medication and 2,032 patients who were treated for high blood pressure but did not have heart attacks. The patients ranged in age from 30 to 79. Patients taking high doses of short-acting calcium channel blockers had a 60% higher risk of heart attack compared to patients taking beta-blockers or angiotensin-converting enzyme (ACE) inhibitors. The risk, however, was small for patients on low doses of calcium channel blockers., Objective.--To assess the association between first myocardial infarction and the use of antihypertensive agents. Design and Setting.--We conducted a population-based case-control study among enrollees of the Group Health Cooperative of Puget Sound (GHC). Patients and Methods.--Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infarction from 1986 through 1993 among women and from 1989 through 1993 among men. Controls were a stratified random sample of hypertensive GHC enrollees, frequency matched to the cases on age, sex, and calendar year. All 623 cases and 2032 controls had pharmacologically treated hypertension. Data collection included a review of the ambulatory medical record and a brief telephone interview of consenting survivors. Antihypertensive therapy was assessed using the GHC's computerized pharmacy database. Results.--The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease. Compared with users of diuretics alone, the adjusted risk ratio of myocardial infarction was increased by about 60% among users of calcium channel blockers with or without diuretics (risk ratio=1.62; 95% confidence interval [CI], 1.11 to 2.34; P=.01). The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a [beta]-blocker. Among these subjects, the use of calcium channel blockers compared with [beta]-blockers was associated with about a 60% increase in the adjusted risk of myocardial infarction (risk ratio=1.57; 95% CI, 1.21 to 2.04; P Conclusions.--In this study of hypertensive patients, the use of short-acting calcium channel blockers, especially in high doses, was associated with an increased risk of myocardial infarction. Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies, including calcium channel blockers, on several important cardiovascular end points. Until these results are available, the findings of this study support the current guidelines from the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure that recommend diuretics and [beta]-blockers as first-line agents unless contraindicated, unacceptable, or not tolerated.

Major clinical trials, which found that low-dose thiazide diuretics reduced the risk of stroke and coronary heart disease, influenced the use of the antihypertensive medicine for older adults in clinical practice, especially among women. The portion which began diuretic therapy rose from 35.9% to 47.5%, following the publication of the clinical trials. The number of patients beginning antihypertensive drug therapy were 157 for the first study period, 142 for the second, and 120 for the third. Among patients who were continuous users of hypertensive medicine, the use of beta-blockers and diuretics decreased over the study period of three years. The use of calcium channel blockers increased in each of the three study periods, however the rate of increase dropped between the first study period and the third., Objective. - To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults. Design. - In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3. Results. - Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P=.04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, [beta]-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P

Postmenopausal women who have hypertension, use hormone replacement therapy, and have a gene mutation that predisposes them to produce blood clots have over 10 times the risk of having a heart attack compared to women with none of those risk factors. This was the conclusion of a study of 955 postmenopausal women, 232 of whom had a heart attack.

Surrogate end points are often used in clinical trials of drugs to treat cardiovascular disease. Ideally, patients in a clinical trial should be followed until they die from the disease. However, this would take so long and require so many patients that doctors began using surrogate end points. Surrogate end points are usually physiological measurements such as blood cholesterol levels. If a drug lowers blood cholesterol levels, doctors assume it will also lower mortality rates from heart disease. However, the withdrawal of the anti-obesity drug dexfenfluramine illustrates the dangers of doing short-term clinical trials that focus on surrogate end points.

The article presents a study that examined the association between atrial fibrillation (AF) and increased risk of sudden cardiac death (SCD).The study reveals the link between incident AF and increased risk of SCD and non-SCD in the general population. It proposes additional research to identify predictors of SCD in patients with AF.

The article discusses a study which investigated the out-of-hospital predictors of critical illness which may improve triage decisions and facilitate regionalization of critical care. The population-based cohort study involved an emergency medical services (EMS) system in greater King County, Washington. Nontrauma, non-cardiac arrest adult patients who were transported to a hospital from 2002 to 2006 were assessed by the authors. The association between the development of critical illness during hospitalization and the score on a prediction rule is cited.

The article presents information on a medical study done to research the association of genetic variations and nonfatal venous thrombosis in postmenopausal women. According to the article, although the roles of clotting proteins that influence fibrin production have already been researched, this particular study focuses on the role of genetic variation in the risk of venous thrombosis in a perimenopausal and postmenopausal women. The study shows that the only gene associated with the risk is the tissue factor pathway inhibitor gene.

Context Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds. Objective To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers. Design, Setting, and Participants This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year. Main Outcome Measure Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls. Results Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26). Conclusion Our finding that conjugated equine estrogen but not esterified estrogen... [ABSTRACT FROM AUTHOR]

Context: A genetic variant in α-adducin has been associated with renal sodium reabsorption and salt-sensitive hypertension. Whether this genetic variant modifies the effect of diuretic therapy on the incidence of myocardial infarction (MI) and stroke is unknown. Objectives: To estimate the interaction between α-adducin and diuretic therapy on the risk of MI or stroke. Specifically, we hypothesized that in participants with treated hypertension, the risk of MI or stroke associated with diuretic use would be lower in carriers of the adducin variant than in carriers of the adducin wild-type genotype. Design, Setting, and Participants: Population-based case-control study of patients enrolled in a health maintenance organization, treated pharmacologically for hypertension, and genotyped as homozygous carriers of the adducin wild-type genotype or carriers of 1 or 2 copies of the Trp460 variant allele. Cases had a first nonfatal MI (n = 206) or stroke (n = 117) between January 1995 and December 1998. Controls (n = 715) were a stratified random sample of pharmacologically treated hypertensive patients who were matched to MI cases by age, sex, and calendar year. Main Outcome Measure: Risk of the combined outcome of first nonfatal MI or stroke. Results: The adducin variant was present in more than one third of the participants. Among the 653 carriers of the adducin wild-type genotype, diuretic therapy was not associated with the risk of MI or stroke (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.78-1.52). Among the 385 carriers of the adducin variant allele, diuretic therapy was associated with a lower risk of the combined outcome of MI and stroke than other antihypertensive therapies (OR, 0.49; 95% CI, 0.32-0.77). The OR in carriers of the adducin variant was less than half of the OR in carriers of the wild-type genotype (P = .005). The case-control synergy index (SI) was 0.45 (95% CI, 0.26-0.79) for the combined outcome of MI and stroke. The point... [ABSTRACT FROM AUTHOR]

Discusses results of a study assessing the risk of recurrent coronary events in relation to use and recent initiation of postmenopausal hormone therapy in women who survived a first myocardial infarction. Percent risk of coronary event during the first 60 days after starting hormone therapy; Percent reduction of coronary event risk with prolonged hormone use.

The article focuses on a study on the incidence of statin-related rhabdomyolysis with the use of administrative data. A computerized pharmacy data was used to estimate the total person-years of statin use by statin type and dose among the enrollees of Group Health Cooperative (GHC). A total of 22 cases of statin-related rhabdomyolysis were validated among statin users with an ICD-9 code. The researchers concluded that the results could prompt a warning about the use of high-dose simvastatin.