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PubMed2026

Dissecting the shared genetic architecture between migraine subtypes and cardiovascular diseases: a multi-layered genomic analysis.

BACKGROUND: Epidemiological studies have linked migraine to an increased risk of cardiovascular disease (CVD); however, the shared genetic basis and putative causal relationships between migraine subtypes and cardiovascular traits remain poorly understood. METHODS: Leveraging large-scale GWAS summary statistics for migraine phenotypes (overall migraine, migraine with aura [MA], and migraine without aura [MO]) from FinnGen R12, along with seven cardiovascular diseases from publicly available consortia, we conducted a multi-layered genetic analysis. This integrative framework encompassed genetic correlation [linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL)], cross-trait meta-analysis (CPASSOC and PLACO), Bayesian colocalization, summary-data-based Mendelian randomization (SMR) using GTEx v8 eQTL data, and bidirectional two-sample Mendelian randomization (MR). RESULTS: Significant genetic correlations were identified between migraine and multiple cardiovascular traits, with hypertension and coronary artery disease (CAD) showing the most robust associations. MA exhibited broader genetic overlap with cardiovascular diseases than MO, including a notably stronger correlation with ischemic stroke, whereas MO demonstrated a stronger correlation with hypertension. Cross-trait meta-analysis identified 160 pleiotropic loci across 17 of 21 trait pairs. Colocalization analysis confirmed 32 loci harboring shared causal variants, mapped to 13 candidate genes, of which 7 (PHACTR1, LRP1, SOX7, ABO, FHOD3, MEI1, XKR6) were further validated by SMR as exhibiting tissue-specific regulatory effects. Among these, PHACTR1 displayed the broadest pleiotropic profile across migraine phenotypes and vascular diseases. After MR-PRESSO outlier removal, bidirectional MR identified 10 MR-supported associations, two of which (genetic liability to hypertension on overall migraine, and CAD on MA) survived Bonferroni correction, all free of detectable horizontal pleiotropy. Genetic liability to hypertension was associated with increased migraine risk (OR = 1.90, 95% CI 1.25-2.90, P = 2.64 × 10⁻³), atherosclerotic diseases showed subtype-specific effects (inverse for MO, positive for MA), and, in the reverse direction, migraine was associated with increased ischemic stroke risk. CONCLUSIONS: This study provides a comprehensive and systematic characterization of the shared genetic architecture between migraine subtypes and cardiovascular diseases. By identifying pleiotropic genes and bidirectional putative causal relationships with subtype-specific patterns, our findings carry implications for the development of targeted therapeutics and subtype-specific cardiovascular risk stratification.

Humans↗
PubMed2004

Cardiovascular effects of selective cyclooxygenase-2 inhibitors.

Selective cyclooxygenase-2 inhibitors represent a significant advance in the management of inflammatory disorders. They have similar efficacy to nonselective 'conventional' nonsteroidal anti-inflammatory drugs, but a superior gastrointestinal safety profile. However, a significant caveat is the perceived potential of cyclooxygenase-2 inhibitors to cause adverse cardiovascular effects, an issue first raised by the Vioxx Gastrointestinal Outcomes Research (VIGOR) study of rofecoxib (Vioxx, Merck & Co. Inc.). Mechanisms by which cyclooxygenase-2 inhibitors may increase cardiovascular risk are selective inhibition of prostaglandin I2 over thromboxane A2 within the eicosanoid pathway, which promotes thrombosis, and inhibition of prostaglandins E2 and I2 within the kidney, which leads to sodium and water retention and blood pressure elevation. In spite of this, the cardiovascular findings from VIGOR are not firmly supported by observations from large cohort studies and other clinical trials of selective cyclooxygenase-2 inhibitors, including the Celecoxib Long-term Arthritis Safety Study. The two main theories that explain the VIGOR findings are that the comparator used (naproxen; Naprosyn, Roche) is cardioprotective and that very high doses of rofecoxib were used, but at present neither is backed by firm evidence. Indeed, there is now early evidence that selective cyclooxygenase-2 inhibition with celecoxib may even protect against the progression of cardiovascular disease, on the basis that cyclooxygenase-2 mediates key processes in atherothrombosis. Currently, it is not clear what the net cardiovascular effects of cyclooxygenase-2 inhibitors are. The data are inconsistent and at best, speculative. It may be also that celecoxib and rofecoxib differ in their cardiovascular effects. Clarification of these issues is of vital importance given the vast number of patients presently taking both types of cyclooxygenase-2 inhibitors. Therefore, what is clear in this situation is the urgent need for randomized clinical trials designed specifically to examine the impact of selective cyclooxygenase-2 inhibitors on cardiovascular risk.

Cardiotonic Agents↗
PubMed2002

[Combined surgery for cardiovascular disease and general thoracic lesions].

Surgical management of patients with concomitant critical cardiovascular disease and resectable general thoracic lesions is controversial. During a 16-year period (1985 to 2001), 15 patients underwent combined cardiovascular and general thoracic operations, of the 2,459 patients who underwent a cardiovascular operation requiring cardiopulmonary bypass at our institution. Patients had cardiovascular symptoms only and the general thoracic lesions were incidentally found by preoperative chest roentgenograms and/or computed tomography. Because of the cardiovascular disease, a pathological diagnosis was precluded before surgery. All except one descending thoracic aortic operation underwent concurrent pulmonary resection after neutralization of protamine following cardiovascular surgery requiring extracorporeal circulation. Lung pathology consisted of pulmonary bullae (n = 7), primary lung cancer (n = 4), benign lung tumor (n = 2), metastatic lung cancer (n = 1), and thymic cyst (n = 1). The pulmonary operations include bullectomy (n = 7), wedge resection (n = 6), lobectomy (n = 3), and removal of a thymic cyst (n = 1) including 2 staged procedures. The final diagnoses in 4 lung cancer cases were T1. N0M0, stage IA (n = 3) and T2N2M0, stage IIIA (n = 1). All malignancies including metastatic lung cancer, were able to be completely resected. The mean intraoperative bleeding volume for the cases was 997 +/- 221 ml, while mean duration of surgery was 382 +/- 31 minutes. Except for 2 cases required long term ventilatory support, the mean durations of tracheal intubation and ICU stay were 2.2 +/- 0.2 and 3.8 +/- 1.0 days respectively. Except for 1 surgical death, mean survival duration and 5-year survival rate were 59.7 +/- 12.5 (5-177) months and 66.3% respectively. These findings suggest that combined pulmonary resection with cardiovascular surgery is safe and offers a favorable prognosis to a selected group of patients.

Adult↗
PubMed2005

Effects of androgens on the cardiovascular system.

The evidence that men have a greater incidence of coronary artery disease than women of similar age, together with the fact that android fat distribution is associated with a greater incidence of coronary heart disease, have suggested that high testosterone levels are associated with an increased risk for coronary artery disease. The possible causal role of androgens in the development of cardiovascular disease has not been proven and, to date, there are no epidemiological and pathophysiological evidences to support that an hyper-androgenic state or androgen replacement is associated with cardiovascular disease in both sexes. Clinical studies have suggested that physiological testosterone supplementation in ageing males has a positive effect upon lipid profile. Additional potential protective cardiovascular effects of androgens may be related to their effect upon endothelial function and vasomotor tone. Few data are currently available on the correlation between plasma testosterone levels and coronary artery disease in men. Cross-sectional studies reported either reduced or similar plasma testosterone levels and/or androgens in patients with coronary artery disease as compared to controls without cardiovascular symptoms. Epidemiological studies addressing the importance of androgen levels upon cardiovascular mortality and morbidity have gathered inconclusive results. Prospective studies found no significant association between plasma testosterone and cardiac events in both sexes, while most cross-sectional studies have repetitively found an association between hypotestosteronemia and cardiovascular morbidity. In conclusion, androgens in general and testosterone in particular may have some protective effects on the cardiovascular system through their metabolic and direct effects upon human vasculature.

Aged↗
PubMed2006

[Affection of cardiovascular system in diabetic patients with thyroid dysfunctions].

Affection of cardiovascular system is one of the most frequent and--especially in higher age groups--the most serious clinical manifestations of thyroid dysfunction. Moreover, diabetics, mainly type 2 diabetes patients, have a marked predisposition to cardiovascular diseases, especially to atherosclerosis and its visceral complications. Simultaneous occurrence of diabetes mellitus (DM) and thyroid dysfunctions involves a very high risk of development and progression of various forms of cardiovascular diseases. There are two basal aspects of the influence of hypothyreosis on cardiovascular system. Decreasing basal metabolism in the whole organism reduces requirements on the cardiovsuclar system. The second aspect of the influence of hypothyreosis on the cardiovascular system is its atherogenic effect. Hypothyreosis in diabetics accelerates the development of chronic, primarily macroangiopathic complications. As opposed to hypothyreosis, the clinical picture of which is not characterised by cardiovascular system disorders, cardiac involvement in patients with hyperthyreosis is more pronounced. In older diabetics hyperthyreosis is often manifested only by cardiovascular symptomatology. Subclinical hyperthyreosis in DM patients may stimulate cardiac function and increase the risk of atrial fibrillation.

Cardiovascular Diseases↗
PubMed1983

The cardiovascular profile of bupropion.

The cardiovascular profile of bupropion has been assessed in over 700 depressed patients. Most of the studies reviewed were double-blind comparisons with placebo or amitriptyline. Subjects included depressed adult outpatients without cardiovascular disease, elderly patients, and patients with cardiovascular disease. Increased heart rate was seen only with amitriptyline, which also caused a subclinical delay in cardiac conduction. Bupropion did not adversely affect supine or standing blood pressure, and patients with tricyclic-induced orthostatic hypotension did not show orthostasis when treated with bupropion. The incidence of subjective cardiovascular complaints with amitriptyline but not with bupropion exceeded that with placebo. Patients with cardiovascular disease who received bupropion had no change in heart rate or blood pressure compared to baseline; their incidence of cardiovascular complaints was comparable to that of disease-free controls. Finally, five patients who took large amounts of bupropion in suicide attempts showed no distinct cardiovascular abnormalities. Thus, bupropion appears safer than amitriptyline and other tricyclics in patients who are prone to orthostatic hypotension or cardiac conduction disorders, and may have a wider safety margin in overdose.

Adult↗
PubMed1998

A comparison of cardiovascular procedure use between the United States and Canada.

OBJECTIVE: To compare the relative volume and intensity of all types of cardiovascular procedures, noninvasive tests, and diagnostic imaging for all elderly individuals between the United States and the three largest Canadian provinces (Ontario, Quebec, and British Columbia) by patient age. DATA SOURCES: Service volume data for the United States for a one percent random sample of claims obtained from Medicare's National Claims History System. Data for Canada were obtained from the Ministries of Health in the three provinces representing 100 percent of the claims received by each Ministry. STUDY DESIGN: Design is a cross-sectional analysis of 1992 claims data. DATA EXTRACTION METHODS: The volume of cardiovascular services was measured in terms of the relative value units (RVUs) used in the Medicare fee schedule to calculate payments. Services were disaggregated into nine clinical categories, and comparisons were made by type of cardiovascular service and patient age. RESULTS: Overall, cardiovascular procedure RVUs per elderly beneficiary are 53 percent greater in the United States than in Canada. Differences are largest for surgical procedures such as carotid thromboendarterectomy and revascularization procedures and smallest for diagnostic imaging and noninvasive tests. The differences between the countries in the use of cardiovascular procedures increase markedly with age. For example, the United States-to-Canada ratio for PTCA use is 1.87 for persons age 65 to 69, but 7.68 for persons age 80 and older. For CABG, the ratios are 1.36 and 7.16, respectively. CONCLUSIONS: Our findings suggest that global budgets in Canada result in lower levels of cardiovascular service use among the elderly, particularly among the very aged elderly. Patient age appears to play a much more important role in determining the recipients of cardiovascular procedures in Canada than in the United States. Whether these higher rates of procedure use among the very elderly in the United States compared to Canada reflect profligate service use or contribute to improved outcomes is uncertain.

Age Factors↗
PubMed2000

Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients.

BACKGROUND: Current guidelines for the management of hypertension rest almost completely on the measurement of systolic and diastolic blood pressure. However, the arterial blood pressure wave is more correctly described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. OBJECTIVE: To explore the independent roles of pulse pressure and mean pressure as determinants of cardiovascular prognosis in older hypertensive patients. METHODS: This meta-analysis, based on individual patient data, pooled the results of the European Working Party on High Blood Pressure in the Elderly trial (n = 840), the Systolic Hypertension in Europe Trial (n = 4695), and the Systolic Hypertension in China Trial (n = 2394). The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox regression analysis, with stratification for the 3 trials and with adjustments for sex, age, previous cardiovascular complications, smoking, and treatment group. RESULTS: A 10-mm Hg wider pulse pressure increased the risk of major cardiovascular complications; after controlling for mean pressure and the other covariates, the increase in risk ranged from approximately 13% for all coronary end points (P = .02) to nearly 20% for cardiovascular mortality (P = .001). In a similar analysis, mean pressure predicted the incidence of cardiovascular complications but only after removal of pulse pressure as an explanatory variable from the model. Furthermore, the probability of a major cardiovascular end point increased with higher systolic blood pressure; at any given level of systolic blood pressure, it also increased with lower diastolic blood pressure, suggesting that the wider pulse pressure was driving the risk of major complications. CONCLUSIONS: In older hypertensive patients, pulse pressure not mean pressure is the major determinant of cardiovascular risk. The implications of these findings for the management of hypertensive patients should be further investigated in randomized controlled outcome trials in which the pulsatile component of blood pressure is differently affected by antihypertensive drug treatment.

Aged↗
PubMed2004

Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease.

BACKGROUND: Observational epidemiological studies consistently show that individuals who choose to take high amounts of vitamin E through diet or supplements experience cardiovascular benefits, for which basic research provides plausible mechanisms. However, because the size of the postulated benefit is small to moderate, the confounding inherent in observational studies is as great as the effect size. Before the availability of randomized evidence, about 1 in 4 adults was taking vitamin E supplements in the United States. METHODS: We conducted a computerized search of the English-language literature from 1990 to the present and found 7 large-scale randomized trials of the effectiveness vitamin E in the treatment and prevention of cardiovascular disease. Data were available on myocardial infarction, stroke, or cardiovascular death. RESULTS: Six of the 7 trials showed no significant effect of vitamin E on cardiovascular disease. In an overview, vitamin E had neither a statistically significant nor a clinically important effect on any important cardiovascular event (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.94-1.03) or its components: nonfatal myocardial infarction (OR, 1.00; 95% CI, 0.92-1.09), nonfatal stroke (OR, 1.03; 95% CI, 0.93-1.14), or cardiovascular death (OR, 1.00; 95% CI, 0.94-1.05). CONCLUSIONS: The ORs and CIs provide strong support for a lack of statistically significant or clinically important effects of vitamin E on cardiovascular disease. The use of agents of proven lack of benefit, especially those easily available over the counter, may contribute to underuse of agents of proven benefit and failure to adopt healthy lifestyles.

Adult↗
PubMed2005

Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.

CONTEXT: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. OBJECTIVE: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. INTERVENTION: Daily dose of natural source vitamin E (400 IU) or matching placebo. MAIN OUTCOME MEASURES: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. RESULTS: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. CONCLUSION: In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.

Aged↗
PubMed2006

Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability.

CONTEXT: Aerobic fitness, an important predictor of cardiovascular disease and mortality, is difficult to assess by maximal exercise testing in older adults. Extended walking tests have been examined as outcome predictors in medically ill populations but not in community-dwelling older adults. OBJECTIVE: To determine whether an extended walking test predicts poor outcomes in older adults. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study enrolling 3075 community-dwelling adults aged 70 to 79 years living in Pittsburgh, Pa, or Memphis, Tenn. Of those participating in the Health, Aging, and Body Composition Study, 1584 (52%) were women and 1281 (42%) were black. Participants enrolled from March 1997 to April 1998. Ability to complete the long-distance corridor walk and total performance time was assessed at the baseline examination. MAIN OUTCOME MEASURES: Total mortality, incident cardiovascular disease, incident mobility limitation, and mobility disability were ascertained after a mean (SD) of 4.9 (0.9) years. RESULTS: Among patients eligible to exercise, 351 died, 308 had episodes of incident cardiovascular disease, 1116 had occurrences of mobility limitation, and 509 had occurrences of mobility disability. Inability to complete walking 400 m tended to be associated with a higher risk of mortality and incident cardiovascular disease and, after accounting for potential confounders, was associated with incident mobility limitation (212.6 vs 79.1 events/1000 person-years; adjusted hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.58-2.18; P<.001) and mobility disability (85.2 vs 28.8 events/1000 person-years; adjusted HR, 1.95; 95% CI, 1.56-2.44; P<.001). Of those who completed 400 m, each additional minute of performance time was associated with an adjusted HR of 1.29 (95% CI, 1.12-1.48) for mortality, 1.20 (95% CI, 1.01-1.42) for incident cardiovascular disease, 1.52 (95% CI, 1.41-1.63) for mobility limitation, and 1.52 (95% CI, 1.37-1.70) for disability after adjustment for demographics, health behaviors, clinical and subclinical disease, and cardiovascular disease risk factors. Findings were consistent in both men and women and blacks and whites. Among participants who completed the test and after adjusting for potential confounders, those in the poorest quartile of functional capacity (walk time >362 seconds) had a higher risk of death than those in the best quartile (walk time <290 seconds; adjusted HR, 3.23; 95% CI, 2.11-4.94; P<.001). CONCLUSIONS: Older adults in the community who reported no difficulty walking had a wide range of performance on this extended walking test. Ability to do the test and performance were important prognostic factors for total mortality, cardiovascular disease, mobility limitation, and mobility disability in persons in their eighth decade.

Aged↗
PubMed2006

Thyroid status, cardiovascular risk, and mortality in older adults.

CONTEXT: Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system. OBJECTIVE: To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS: A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study. MAIN OUTCOME MEASURES: Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. RESULTS: Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease. CONCLUSION: Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.

Aged↗
PubMed2004

Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis.

OBJECTIVE: Various etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population-based cohort of subjects with RA with that in a cohort of individuals without RA from the same population. METHODS: The RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age- and sex-matched comparison cohort of subjects without RA was assembled. Both cohorts were followed up longitudinally through their complete (inpatient, outpatient) medical records beginning at age 18 years and continuing until death, migration, or January 1, 2001, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m(2) and low BMI as <20 kg/m(2). Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies. RESULTS: RA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23-4.99) compared with non-RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50-2.92) when compared with non-RA subjects who maintained normal BMI throughout followup. CONCLUSION: Among patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.

Aged↗
PubMed2005

The trade-off between cardiovascular and gastrointestinal effects of rofecoxib.

BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Prevention of cardiovascular disease--opportunities for progress.

Steady progress has been made in the prevention of cardiovascular disease. There has been a favorable trend in major risk factor reduction and an average 3% annual decline in cardiovascular disease death rates over the past decade. Yet, CVD death rates still exceed that for many countries and not all segments of the U.S. population have benefited equally. Cardiovascular disease remains the leading cause of death and disability in this country. The role of epidemiologic research and prevention strategies in addressing this issue has been underestimated. Unresolved research questions require further epidemiologic research in order to improve application of known preventive measures and explore other approaches toward the prevention of cardiovascular disease. It is well established that attention to life-style changes and pharmacologic approaches can prevent cardiovascular disease in those at high risk and reduce the likelihood of subsequent cardiac events among patients with known cardiovascular disease. Furthermore, small changes in the distribution of risk factors through community intervention can have tremendous impact on cardiovascular disease morbidity and mortality. Preventive research requires an appropriate framework and plan to satisfy or exceed the needs in keeping with the national goals for Healthy People 2000. The National Heart, Lung, and Blood Institute has addressed this issue by creating a Task Force to develop research priorities for epidemiology and prevention.

Arteriosclerosis↗
PubMedDate not supplied

Impact of unhealthy behaviors on cardiovascular mortality in Finland, 1978-1993.

BACKGROUND: Our aim was to study how combinations of three unhealthy behaviors (smoking, physical inactivity, and use of dairy fat) and an index describing their number were associated with the risk of cardiovascular mortality in a society showing remarkable improvement in health behaviors. METHODS: The material consisted of random samples of annual adult health behavior surveys from 1978 to 1991; included were 8,869 men and 10,105 women ages 45 to 64 years. The mortality follow-up covered Years 1978 to 1993. The study period was divided into four phases on the basis of number of deaths and timing of health behavior changes. Poisson multivariate models were used to determine the risk of cardiovascular mortality by all combinations of unhealthy behaviors and the index. In the models age, education, chronic morbidity, and body mass index were adjusted for. RESULTS: Each unhealthy behavior was found to be a risk factor for cardiovascular mortality when the whole study period was examined. Among men, daily smoking was a significant predictor of cardiovascular mortality in the first three phases, among women in the first and third phase. Among men physical inactivity became significant only in the last phase, among women in all except the last phase. The combinations of physical inactivity with use of dairy fat or with smoking were more significant for women than for men. The combination of smoking and use of dairy fat was significant only for men. The association of the index with cardiovascular mortality was slightly stronger among women than among men. CONCLUSIONS: The predictive values of unhealthy behaviors on cardiovascular mortality changed by period depending on their frequency. The combinations of unhealthy behaviors are to be preferred over the index in description of lifestyle determinants of cardiovascular mortality.

Cardiovascular Diseases↗
PubMed1989

Role of histamine receptor in mesencephalic nucleus dorsalis raphe in cardiovascular regulation.

The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H2-receptor blocker, cimetidine (10 micrograms) resulted in hypertension and tachycardia while H1-receptor antagonist, mepyramine (10 micrograms) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H1 and H2 receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 micrograms) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on alpha adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria.

Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 microg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 microg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20% for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 +/- 10 vs 70 +/- 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8%; odds ratio 3.96, 95% CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14% p < 0.01) and hyperlipidaemia (49 vs 26% p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K(itt) index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.

Adult↗