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Physician-performed point-of-care echocardiography using a laptop platform compared with physical examination in the cardiovascular patient.

OBJECTIVES: The purpose of this study was to compare the results of physical examinations (PEs) performed by board-certified cardiologists with the results of point-of-care (POC) echocardiography in a group of patients with cardiovascular disease. BACKGROUND: Although cardiovascular PE is crucial in the evaluation of patients with suspected heart disease, the skills required to diagnose abnormal cardiovascular findings have been declining. Echocardiography is a powerful noninvasive cardiovascular diagnostic tool; however, echocardiographic evaluation of patients is not performed at the time of patient encounter (POC echocardiography), beacuse current platforms are cumbersome and expensive for individual physician use. The development of miniaturized echocardiographic equipment has the potential to overcome some of these limitations. METHODS: Thirty-six subjects had a complete cardiovascular examination by four board-certified cardiologists. The physicians subsequently imaged each patient using a miniaturized echocardiographic platform. The yield of PE and POC echocardiography were compared using a complete echocardiographic study as the gold standard, performed on an upper-end platform. RESULTS: Cardiac examination failed to detect 59% of the overall cardiovascular findings. Physician-performed echocardiography with the prototype device missed 29% of the overall cardiovascular pathology. When considering only the major cardiovascular findings, the cardiologists' PEs still failed to correctly detect 43%. Point-of-care echocardiography reduced this to 21% without significant interphysician variation. CONCLUSIONS: Point-of-care echocardiography using a miniaturized echocardiographic platform substantially improved the detection of important cardiovascular pathology compared with PE. Use of this device by a cardiovascular specialist with training in echocardiography as a routine adjunct to PE appears to be useful.

Echocardiography↗

Usefulness of QT-interval parameters for cardiovascular risk stratification in type 2 diabetic patients with arterial hypertension.

QT-interval parameters are potential indicators of increased cardiovascular risk. We evaluated prospectively their prognostic value, in relation to other risk markers, for cardiovascular fatal and nonfatal events in a cohort of 271 hypertensive type 2 diabetic outpatients. QT intervals were measured from 12-lead standard ECGs obtained on admission and maximum rate-corrected QT-interval duration and QT-interval dispersion (QTd) calculated. Clinical and laboratory data and 2-D echocardiograms (available in 126 patients) were recorded. Survival analyses included Kaplan-Meier survival curves, uni and multivariate Cox proportional-hazards models. After a median follow-up of 55 months (range 2-84), 68 total fatal or nonfatal cardiovascular events and 34 cardiovascular deaths (24 of them from cardiac causes) were observed. In multivariate Cox analysis, QTd was an independent predictor for total cardiovascular events (HR: 1.16, 95% CI: 1.01-1.34, for each 10 ms increments) and for cardiac deaths (HR: 1.28, 95% CI: 1.01-1.60). Other independent risk indicators for cardiovascular morbidity and mortality were echocardiographic left ventricular hypertrophy (Echo-LVH), serum triglycerides, presence of pre-existing cardiac and peripheral arterial disease, age, diabetes duration, heart rate and the presence of frequent ventricular premature contractions on ECG. The combination of QTd and Echo-LVH improved cardiovascular risk stratification compared with either alone, the presence of both prolonged QTd (>65 ms) and Echo-LVH was associated with a 3.2-fold (95% CI: 1.7-6.1) increased risk of a first cardiovascular event and a 5.9-fold (95% CI: 2.1-16.4) increased risk of cardiovascular death. Thus, QT provided additive prognostic information for cardiovascular morbidity and mortality beyond that obtained from conventional risk markers, including Echo-LVH, in type 2 diabetic patients with arterial hypertension.

Adult↗

A prospective study on cardiovascular events after acute pulmonary embolism.

AIMS: To evaluate the incidence of cardiovascular events in the long-term clinical course of patients with a first episode of symptomatic, objectively confirmed pulmonary embolism. METHODS AND RESULTS: Three hundred and sixty patients with a first episode of pulmonary embolism were included in a prospective study: 209 with idiopathic pulmonary embolism and 151 with pulmonary embolism associated with transient risk factors. The study outcomes were cardiovascular events (recurrent venous thrombo-embolism, acute myocardial infarction, stroke, sudden otherwise unexplained death), cardiovascular death, and death due to any cause. The median follow-up was 38 months. Sixty-four patients had at least one cardiovascular event (5.5% patient-year). Recurrent venous thrombo-embolism occurred in 45 patients (3.9% patient-year), acute myocardial infarction in 12 patients (1.0% patient-year), stroke in six patients (0.5% patient-year), and sudden otherwise unexplained death in four patients (0.3% patient-year). A cardiovascular event occurred in 47 patients with idiopathic pulmonary embolism (7.5% patient-year) and in 17 patients with pulmonary embolism associated with transient risk factors (3.1% patient-year) (RR 2.0; 95% CI 1.20-3.34; P=0.006). Twenty patients with idiopathic pulmonary embolism (3.2% patient-year) and two patients with pulmonary embolism associated with transient risk factors (0.4% patient-year) presented an arterial cardiovascular event (RR 7.2; 95% CI 1.71-30.45; P=0.001). Thirty-three patients died (9.2%). Cardiovascular mortality and cancer mortality accounted for 42.4 and 21.2% of overall mortality, respectively. Idiopathic pulmonary embolism was an independent predictor of cardiovascular events after adjusting for age. CONCLUSIONS: Cardiovascular events are more common in patients with idiopathic pulmonary embolism than in patients with pulmonary embolism associated with transient risk factors. Cardiovascular events are the major cause of death in patients with idiopathic pulmonary embolism.

Acute Disease↗

Microalbuminuria in type 2 diabetes: an independent predictor of cardiovascular mortality.

BACKGROUND: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. AIMS: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. METHODS: In a prospective longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. RESULTS: The prevalence of urine albumin of 30-300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L as compared to < 30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22-2.57, p = 0.002) for all causes, 2.34 (95% CI 1.38-3.99, p = 0.002) for cardiovascular and 1.78 (95% CI 0.97-3.26, p = 0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. CONCLUSIONS: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.

Albuminuria↗

Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study.

BACKGROUND: Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events than low-density lipoprotein cholesterol. METHODS AND RESULTS: We studied 9231 asymptomatic women and men from the Danish general population followed prospectively for 8 years and observed the following incident events: ischemic heart disease 591, myocardial infarction 278, ischemic cerebrovascular disease 313, ischemic stroke 229, and any ischemic cardiovascular event 807. Women with apoB in the upper versus the lower tertile had hazard ratios for ischemic heart disease of 1.8 (1.2 to 2.5), for myocardial infarction 2.6 (1.4 to 4.7), and for any ischemic cardiovascular event 1.8 (1.3 to 2.3), and men had hazard ratios for ischemic heart disease of 1.9 (1.5 to 2.6), for myocardial infarction 2.4 (1.5 to 3.6), and for any ischemic cardiovascular event 1.6 (1.3 to 2.1). Women had similar hazard ratios for ischemic cerebrovascular disease and ischemic stroke. ApoB had a higher predictive ability than low-density lipoprotein cholesterol in the prediction of ischemic heart disease, myocardial infarction, any ischemic cardiovascular event, and any nonfatal ischemic cardiovascular event in both genders (P=0.03 to <0.001). Finally, in smokers older than 60 years with systolic blood pressure >160 mm Hg, apoB contributed 11% in women and 15% in men to the increase in absolute 10-year risk from the lower to the upper apoB tertile. CONCLUSION: ApoB predicts ischemic cardiovascular events in both genders, and is better than low-density lipoprotein cholesterol in this respect. We suggest that prediction of future ischemic cardiovascular events could be improved by measuring apoB.

Adult↗

A population-based study on well-being in the very old: the role of cardiovascular diseases and drugs.

Cardiovascular diseases constitute the most common health problems in very old people. Consequently, cardiovascular drugs are the medicines that are most frequently used by elderly subjects. Although many studies have examined the physiological effect and adverse reactions of these drugs, knowledge on their effect on emotional well-being is missing. The present study aims to examine the association between cardiovascular diseases and their medical treatment on the emotional well-being of very old people. We investigated a representative group of elderly subjects gathered from a population-based study (n=235). Participants were 84 years or older and cognitively intact (mini-mental state examination (MMSE) > or =24 points). Well-being was assessed with the positive and negative affect schedule (PANAS), measuring different mood categories. Cardiovascular diseases were diagnosed following the International Classification of Diseases. In this population the prevalence of cardiovascular diseases was high (62%). Multivariate regression analysis showed that while being affected by a cardiovascular disease did not affect the emotional well-being of the subjects (PANAS-PA, p=0.171; PANAS-NA, p=0.209), the use of some cardiovascular drugs showed an association. Cardiac glycosides (p=0.006) and nitrates (p=0.008) were associated with increased negative feelings. Due to high prevalence of cardiovascular diseases and use of cardiovascular medicines, this finding has relevance on the quality of life of elderly people. However, due to the nature of this study we cannot assess cause-effect relationship of this positive association. Therefore, the present findings suggest that there is a need for clinical studies in this increasing and limited studied age group.

Aged↗

Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes.

Impaired glucose metabolism is associated with an increased risk of cardiovascular events and cardiovascular-associated mortality. Postprandial hyperglycaemia is one of the earliest identifiable indicators of impaired glucose control. It contributes to the progression from impaired glucose tolerance to overt type 2 diabetes and exacerbates chronic hyperglycaemia in established diabetes. It is also an independent risk factor for cardiovascular disease in patients with impaired glucose tolerance and type 2 diabetes. Thus, an important strategy to reduce cardiovascular risk in patients with impaired glucose metabolism is to reduce postprandial glucose excursions. Acarbose, an alpha (alpha)-glucosidase inhibitor, reduces postprandial hyperglycaemia by delaying carbohydrate absorption from the small intestine. This mechanism of action provides glycaemic control without increasing insulin levels and exacerbating coexisting cardiovascular risk factors. The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) assessed the ability of acarbose to reduce cardiovascular risk. In this study of 1429 individuals with impaired glucose tolerance, acarbose therapy reduced the risk of any cardiovascular event by 49% (P=0.03), of an acute myocardial infarction by 91% (P=0.02) and of developing hypertension by 34% (P=0.006). Furthermore, a retrospective meta-analysis of randomised studies of acarbose in type 2 diabetes patients showed that acarbose therapy reduced the risk of any cardiovascular event by 35% (P=0.006) and the risk of a myocardial infarction by 64% (P=0.012). These results suggest that acarbose is useful in reducing the risk of cardiovascular events in patients with impaired glucose metabolism.

Acarbose↗

The aged cardiovascular risk patient.

It is mostly acknowledged that 'normal' or 'healthy' ageing of the cardiovascular system is distinct from the increasing incidence and severity of cardiovascular disease with advancing age (e.g. hypertension, ischaemic heart disease and congestive heart failure). It is also recognized that chronological and biological age may differ considerably. Nevertheless, even in the absence of overt coexisting disease, advanced age is always accompanied by a general decline in organ function, and specifically by alterations in structure and function of the heart and vasculature that will ultimately affect cardiovascular performance. Actual biological age is thus the net result of the interaction between age-related and concomitant disease-associated changes in organ function. As cardiovascular performance at a given moment is the net result of interactions between heart rate, intrinsic contractility, diastolic and systolic function, ventricular afterload and coronary perfusion, it is important to be aware of the age-related changes in each of these variables, independent of disease, as they determine cardiac performance at rest and its response to stress in the elderly. The most relevant age-related changes in cardiovascular performance for perioperative management are the stiffened myocardium and vasculature, blunted beta-adrenoceptor responsiveness and impaired autonomic reflex control of heart rate. These changes are of little clinical relevance at rest, but may have considerable consequences during superimposed cardiovascular stress. Such stress can take the form of increased flow demand (as in exercise or postoperatively), demand for acute autonomic reflex control (as in change of posture) or severe disease (as during myocardial ischaemia, tachyarrhythmias or uncontrolled hypertension). It may interfere with diastolic relaxation (i.e. ventricular filling), systolic contraction (i.e. ventricular emptying) and vasomotor control (i.e. arterial pressure homeostasis). Three factors contribute most of the increased perioperative risk related to advanced age. First, physiological ageing is accompanied by a progressive decline in resting organ function. Consequently, the reserve capacity to compensate for impaired organ function, drug metabolism and added physiological demands is increasingly impaired. Functional disability will occur more quickly and take longer to be cured. Second, ageing is associated with progressive manifestation of chronic disease which further limits baseline function and accelerates loss of functional reserve in the affected organ. Some of the age-related decline in organ function (e.g. impaired pulmonary gas exchange, diminished renal capacity to conserve and eliminate water and salt, or disturbed thermoregulation) will increase cardiovascular risk. The unpredictable interaction between age-related and disease-associated changes in organ functions, and the altered neurohumoral response to various forms of stress in the elderly may result in a rather atypical clinical presentation of a disease. This may, in turn, delay the correct diagnosis and appropriate treatment and, ultimately, worsen outcome. Third, related to the increased intake of medications and altered pharmacokinetics and pharmacodynamics, the incidence of untoward reactions to medications, anaesthetic agents, and medical and surgical interventions increases with advancing age. On the basis of various clinical studies and observations, it must be concluded that advanced age is an independent predictor of adverse perioperative cardiac outcome. It is to be expected that the aged cardiovascular risk patient carries an even higher perioperative cardiac risk than the younger cardiovascular risk patient. Although knowledge of the physiology of ageing should help reduce age-related complications, successful prophylaxis is hindered by the heterogeneity of age-related changes, unpredictable physiological and pharmacological interactions and diagnostic difficultie

Age Factors↗

[Impact on cardiovascular health results of the introduction of the clinical governance contract into primary care in Tarragona].

OBJECTIVE: The objectives of this study are: 1) to determine the improvement in the cardiovascular health of the population after the introduction of the clinical governance contract for primary care team professionals in Tarragona-Reus and the Terres de l'Ebre area (Tarragona province, Spain); 2) to identify the factors predictive of better cardiovascular health after the introduction of the clinical governance contract. The introduction of the clinical governance contract, which is based on professional leadership, feed-back of care information, and monitoring of indicators of cardiovascular risk based on scientific evidence and concretised in clinical practice guidelines, will improve the cardiovascular health results of the reference population. Improvements in indicators of procedure and result are specified in "Material and methods." DESIGN: This is a before-and-after, multi-centre study. SETTING: Primary health care. PARTICIPANTS: Thirty health centres (all the primary care Centres in the area). MAIN MEASUREMENTS: Characteristics of the centre. Variables in procedures: indicators of good care practice, calculation of cardiovascular risk, application of clinical practice guidelines (hypertension, diabetes, lipaemia, tobacco and cardiovascular risk) and quality standards for drug prescription. Result variables: cardiovascular risk figures, number of ongoing care visits, hospital emergencies and admissions for angina, heart attack or stroke, and risk factor screenings of the population. DISCUSSION: This study is useful, in that clinical governance aims to be a dynamic device to bring professionals into the leadership of health care management and, through monitoring indicators and feeding the findings back to the professionals, to improve health care quality. The study aims to show that management strategy can improve the population s cardiovascular health. The originality of the study lies in the development of a new tool of evaluation based on a novel management strategy for measuring cardiovascular health findings.

Adult↗

Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis.

BACKGROUND: In SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17&#x2009;604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor agonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups. METHODS: In this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104, 208 weeks) using multiple approaches, including Cox modeling. RESULTS: Baseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACE. The risk of MACE increased across baseline hsCRP level <2, 2-<10, and &#x2265;10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACE across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACE. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT. CONCLUSIONS: In SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03574597.

Humans↗

Risk of Cardiovascular Disease Mortality in Patients With Diagnosed Cancer and Associated Genetic and Proteomic Mechanisms: A UK Biobank-Based Cohort Study.

BACKGROUND: Previous studies have identified a link between cancer and cardiovascular disease; however, the underlying genetic and proteomic mechanisms remain unclear. Therefore, this study aimed to investigate the association between cancer diagnosis and cardiovascular mortality and to explore the potential mechanisms involved. METHODS: A total of 379&#x2009;944 participants without cardiovascular disease at baseline, including 65&#x2009;047 individuals with cancer, were recruited from the UK Biobank database. The primary end point was cardiovascular death. Multivariate Cox regression was performed to evaluate the risk of cardiovascular death in populations with and without cancer. Genome-wide association studies, phenome-wide association studies, and proteomic analyses were applied to investigate the underlying genetic and proteomic mechanisms. RESULTS: Multivariate Cox regression analysis showed an increased risk of cardiovascular death in the group with cancer (hazard ratio, 1.50 [95% CI, 1.40-1.61]) after multivariable adjustment. Proteomic analysis confirmed a strong association between cancer and cardiovascular disease, primarily involving pathways related to complement and coagulation cascades, and various inflammatory processes. In contrast, genome-wide association studies and phenome-wide association studies revealed only a limited number of shared genetic variations between cancer and cardiovascular conditions, such as hypertension and cardiac dysrhythmias. CONCLUSIONS: Cardiovascular risk is increased in patients with cancer and may be related to altered expression of inflammation- and coagulation-related proteins. In clinical practice, it is recommended to emphasize the management of endocrine, kidney, and inflammation-related risk factors in the population with cancer.

Humans↗

Issues influencing development of the Canadian Cardiovascular Information Network.

The 1995 Consensus Conference of the Canadian Cardiovascular Society on "Indications for and Access to Revascularization" recommended that Canadian centres with invasive cardiovascular facilities should participate in a national observational database that monitors the selection of patients, as well as evaluate outcomes. The Canadian Cardiovascular Society, the Heart and Stroke Foundation of Canada, and Health Canada with IBM as a partner, initiated a process to identify factors influencing the development of the Canadian Cardiovascular Information Network. IBM's "Business Discovery Methodology" was adapted for health care. Structured interviews with representatives of health organizations, cardiovascular databases and research institutes were conducted across Canada, followed by a workshop to identify goals, issues and challenges. Participants identified goals for a cardiovascular database (eg, evidence-based decision-making), project related issues (eg, respecting the integrity of existing databases) and health care related issues (eg, cardiac waiting lists). Challenges included initial mistrust between representatives of provincial cardiovascular databases and national agencies, and a lack of sustained funding. A Project Team was formed to address 'cardiac waiting lists'. Analysis of Alberta and Ontario data identified differences in definitions, such as when the waiting time for bypass surgery began, that impeded detailed comparisons. Development of a centralized national database was not feasible at this time for political, technical and financial reasons. However, provincial cardiovascular database representatives agreed to work together and to share aggregate data and analyses. A first step toward developing a national surveillance system for cardiovascular services will be achieving consensus about standardizing data definitions. This process will require sustained funding.

Canada↗

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

BACKGROUND: Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. OBJECTIVE: To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. METHODS: We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. RESULTS: Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). CONCLUSIONS: Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.

Aged↗

Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.

Biomarkers↗

Hemoglobin A1c level and future cardiovascular events among women.

BACKGROUND: Available data suggest that hemoglobin A(1c) (A(1c)), also known as glycosylated hemoglobin, levels may be related to cardiovascular risk in the general population without diabetes mellitus. We sought to test this hypothesis prospectively in a cohort of women without overt cardiovascular disease. METHODS: We conducted a nested case-control study of the Women's Health Study cohort. We identified 464 case patients with incident myocardial infarction, stroke, or coronary revascularization and 928 unmatched control subjects who remained free of cardiovascular events at case diagnosis. The mean follow-up was 7 years. RESULTS: Of the overall study population, 136 had a history of diabetes mellitus or an overtly elevated baseline A(1c) level (>6.4%) and were excluded from the primary analyses. Among women without diabetes mellitus or an elevated baseline A(1c) level, mean +/- SD baseline levels of A(1c) were significantly higher among future cases than controls (5.47% +/- 0.27% vs 5.37% +/- 0.22%; P<.001). The crude relative risks (RRs) of incident cardiovascular events for increasing quartiles of A(1c) were 1.00, 0.98, 1.33, and 2.25 (95% confidence interval [CI] for the highest vs the lowest quartile, 1.59-3.18). The A(1c) levels correlated with several other traditional cardiovascular risk factors, and in fully adjusted models, the predictive effect of A(1c) was attenuated and not significant (RR for the highest vs the lowest quartile, 1.00; 95% CI, 0.65-1.54). In contrast, in the population including women with diabetes mellitus at enrollment, diabetes mellitus (RR, 4.97; 95% CI, 2.81-8.77) remained a strong independent determinant of cardiovascular risk in fully adjusted analyses, while A(1c) levels did not (RR for the highest vs the lowest quartile, 1.11; 95% CI, 0.73-1.71). CONCLUSIONS: The A(1c) level is associated with future cardiovascular risk among women without diabetes mellitus, but this relationship is largely attributable to a strong correlation with other cardiovascular risk factors. In contrast, diabetes mellitus is a strong independent determinant of cardiovascular risk, even after adjustment for A(1c) levels.

Body Mass Index↗

Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population: a review and qualitative overview of the prospective cohort studies.

BACKGROUND: In certain subgroups of patients, prolongation of the QTc interval may increase total and cardiovascular mortality due to life-threatening ventricular arrhythmias and sudden death. Nonetheless, whether modest prolongation of the QTc interval in the general population has clinical importance remains unclear. METHODS: We conducted a literature search from 1990 forward to identify all published prospective cohort studies evaluating the association between prolonged QTc interval and risks of total and cardiovascular mortality as well as sudden death. We reviewed each of the studies individually and then conducted a qualitative overview. RESULTS: The 7 prospective cohort studies identified included 36 031 individuals. There were 2677 (8.7%) individuals with prolonged QTc interval, defined as 440 milliseconds or greater. Whereas 1 study reported no association between prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistent associations overall as well as across subgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascular mortality and sudden death were also inconsistent. In the overview, the only consistent findings were for the subgroup of patients with prior cardiovascular disease, in which relative risks ranged from 1.1 to 3.8 for total mortality, from 1.2 to 8.0 for cardiovascular mortality, and from 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absent or greatly attenuated; specifically, relative risks ranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascular mortality, and from 1.3 to 2.4 for sudden death. CONCLUSIONS: There was no consistent evidence for increased risks of total or cardiovascular mortality or of sudden death, except perhaps for patients with prior cardiovascular disease. In the general population, if QTc interval prolongation is associated with any increase in mortality, that risk is likely to be small and difficult to detect reliably.

Cardiovascular Diseases↗

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

CONTEXT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. OBJECTIVE: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. DESIGN: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. SETTING: Family practices and outpatient clinics at primary and secondary referral hospitals. PARTICIPANTS: A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. INTERVENTIONS: For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). MAIN OUTCOME MEASURES: Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. RESULTS: After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

Aged↗

Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.

CONTEXT: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. OBJECTIVE: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. INTERVENTION: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. MAIN OUTCOME MEASURES: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. RESULTS: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). CONCLUSIONS: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.

Adrenergic beta-Antagonists↗