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Cardiovascular malformations among preterm infants.

OBJECTIVE: Preterm birth and cardiovascular malformations are the 2 most common causes of neonatal and infant death, but there are no published population-based reports on the relationship between them. We undertook this study to determine the prevalence and spectrum of cardiovascular malformations in a preterm population, the prevalence of prematurity among infants with cardiovascular malformations, and the influence of prematurity and cardiovascular malformations on outcomes. METHODS: We based the study on the population of the former Northern Health Region of England. We identified all live-born infants with cardiovascular malformations diagnosed in the first 1 year of life from the regional pediatric cardiology database, which includes the gestational age and details of the diagnosis. We limited ascertainment to malformations diagnosed by the age of 12 months. Infants with isolated patent ductus arteriosus or atrial septal defect were excluded, to avoid ascertainment bias. Infants with ventricular septal defect were classified according to whether they required surgery in the first 1 year. There are no population data on gestational ages for all births in our population for the era of this study; therefore, we used data published in the literature for populations similar to our own to predict that 0.4% of live births occur at <28 weeks of gestation, 0.9% at 28 to 31 weeks, and 6% at 32 to 36 weeks. Overall, 7.3% of live-born infants are preterm. RESULTS: Of 521619 live-born infants in 1987-2001, 2964 had cardiovascular malformations (prevalence: 5.7 cases per 1000 live births). Cardiovascular malformations were present at 5.1 cases per 1000 term infants and 12.5 cases per 1000 preterm infants. The odds ratio (OR) for a cardiovascular malformation in prematurity was 2.4 (95% confidence interval [CI]: 2.2-2.7). We found that 474 infants (16%) with cardiovascular malformations were born at <37 weeks of gestation, giving an OR for prematurity among infants with a cardiovascular malformation of 2.4 (95% CI: 2.2-2.7). More infants were born preterm with diagnoses of pulmonary atresia with ventricular septal defect (23%), complete atrioventricular septal defect (22%), and coarctation of the aorta, tetralogy of Fallot, and pulmonary valve stenosis (each 20%). Fewer were born preterm with diagnoses of pulmonary atresia and intact ventricular septum (7%), transposition of the great arteries (8%), and single ventricle (9%). We found that 18% of infants with ventricular septal defect requiring surgery were preterm, compared with 13% in the nonsurgical group. Preterm infants with ventricular septal defect required surgery in 30% of cases, compared with 23% of term infants with ventricular septal defect. These figures show that the excess of cardiovascular malformations among preterm infants cannot be explained by greater ascertainment of minor ventricular septal defects. In our denominator population, 646 live-born infants were recognized as having trisomy 21, and gestational age data were available for 609. Of these, 149 (25%; 95% CI: 21-28%) were preterm. Approximately two thirds of infants with complete atrioventricular septal defect have trisomy 21. Complete atrioventricular septal defect was no more common among preterm infants with trisomy 21 (16%) than among term infants with trisomy 21. However, the increased incidence of prematurity among infants with trisomy 21 probably explains some of the excess of preterm births among infants with complete atrioventricular septal defect. Only 4 (11%) of 38 infants with 22q11 deletion were born preterm. None of those infants had pulmonary atresia with ventricular septal defect; therefore, 22q11 deletion does not explain the excess of preterm births in pulmonary atresia with ventricular septal defect. The OR for death in the first 1 year in the presence of a cardiovascular malformation was 4.4 (95% CI: 3.1-5.5) overall; ORs were 1.8 at <28 weeks of gestation, 3.7 at 28 to 31 weeks, 11.0 at 32 to 36 weeks, and 35.6 at term. CONCLUSIONS: This study showed that preterm infants have more than twice as many cardiovascular malformations as do infants born at term and that 16% of all infants with cardiovascular malformations are preterm. It also showed, not surprisingly, that there is an increased mortality rate among infants born preterm with a cardiovascular malformation. The additional effect of cardiovascular malformations on mortality rates is most marked for term and near-term infants, for whom mortality rates are otherwise low. The excess of cardiovascular malformations among preterm infants is intriguing but not easy to explain. Previous studies of birth weight among infants with cardiovascular malformations reported a significant increase in the likelihood of being small for gestational age among infants with tetralogy of Fallot, complete atrioventricular septal defect, hypoplastic left heart, or large ventricular septal defect. There is an obvious relationship between birth weight and gestational age, and those studies also showed an increased prevalence of prematurity among infants with tetralogy of Fallot, pulmonary stenosis, aortic stenosis, coarctation of the aorta, complete atrioventricular septal defect, or ventricular septal defect. There is also a high prevalence of cardiovascular malformations among late stillbirths, with major differences in the number and spectrum of cardiovascular malformations, compared with those seen in postnatal life. In particular, there is a greater incidence of coarctation of the aorta, double-inlet left ventricle, hypoplastic left heart, truncus arteriosus, double-outlet right ventricle, and atrioventricular septal defect among stillbirths. This spectrum of malformations is similar to that in our study and to those in other reports. Whether the increased prevalence of cardiovascular malformations among preterm infants and the increase in stillbirths suggest clues to the cause is difficult to say. The influence of preterm birth should be taken into account in risk assessment and risk stratification for surgical repair.

Heart Defects, Congenital↗

Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial.

CONTEXT: Raloxifene, a selective estrogen receptor modulator, improves cardiovascular risk factors, but its effect on cardiovascular events is unknown. OBJECTIVE: To determine the effect of raloxifene on cardiovascular events in osteoporotic postmenopausal women. DESIGN: Secondary analysis of data from the Multiple Outcomes of Raloxifene Evaluation trial, a randomized, double-blind, placebo-controlled trial conducted between November 1994 and September 1999. SETTING: Outpatient and community settings at 180 sites in 25 countries. PARTICIPANTS: A total of 7705 osteoporotic postmenopausal women (mean age, 67 years). INTERVENTION: Patients were randomly assigned to receive raloxifene, 60 mg/d (n = 2557), or 120 mg/d (n = 2572), or placebo (n = 2576) for 4 years. MAIN OUTCOME MEASURES: Cardiovascular events, including coronary events (myocardial infarction, unstable angina, or coronary ischemia) and cerebrovascular events (stroke or transient ischemic attack), collected as safety end points and subsequently adjudicated by a cardiologist blinded to therapy. Cardiovascular risk at study entry was determined by the presence of multiple cardiovascular risk factors or prior coronary events or revascularization procedure. RESULTS: In the overall cohort, there were no significant differences between treatment groups in the number of combined coronary and cerebrovascular events: 96 (3.7%) with placebo, 82 (3.2%) with 60 mg/d of raloxifene, and 94 (3.7%) with 120 mg/d of raloxifene. Relative risks (RRs) were 0.86 (95% confidence interval [CI], 0.64-1.15) and 0.98 (95% CI, 0.74-1.30) for 60 mg/d and 120 mg/d of raloxifene, respectively. Similar results were obtained when coronary and cerebrovascular events were analyzed separately. Among the subset of 1035 women with increased cardiovascular risk at baseline, those assigned to raloxifene had a significantly lower risk of cardiovascular events compared with placebo (RR, 0.60; 95% CI, 0.38-0.95 for both raloxifene groups). The number of cardiovascular events during the first year was not significantly different across groups in the overall cohort (P =.94), or among women at increased cardiovascular risk (P =.86) or with evidence of established coronary heart disease (P =.60). CONCLUSIONS: Raloxifene therapy for 4 years did not significantly affect the risk of cardiovascular events in the overall cohort but did significantly reduce the risk of cardiovascular events in the subset of women with increased cardiovascular risk. There was no evidence that raloxifene caused an early increase in risk of cardiovascular events. Before raloxifene is used for prevention of cardiovascular events, these findings require confirmation in trials with evaluation of cardiovascular outcomes as the primary objective.

Aged↗

Cardiovascular risk in patients with mild renal insufficiency: implications for the use of ACE inhibitors.

We review the evidence linking mild renal insufficiency (MRI) with increased cardiovascular risk. MRI is associated with a number of cardiovascular risk factors, including nighttime hypertension, and increased levels of lipoprotein (a), homocysteine, asymmetric dimethyl-arginine, and inflammation and insulin resistance markers and mediators. Epidemiologic evidence associates coronary artery disease and nephrosclerosis, a frequent cause of early renal insufficiency in the elderly. In a middle-aged general population MRI was found in 8% of women and 9% of men, but was not associated with cardiovascular disease. Nonetheless, in a representative sample of middle-aged British men the risk of stroke was 60% higher for the sub-group with MRI: in people at high cardiovascular risk (mostly coronary disease), the HOPE study found a 2-fold (unadjusted) or 1.4-fold (adjusted) higher incidence of cardiovascular outcomes with MRI. The combined incidence of cardiovascular death, myocardial infarction and stroke increased with the level of serum creatinine. Several studies have examined the cardiovascular risk associated with MRI in hypertension. In HDFP, as in HOPE, cardiovascular mortality increased with serum creatinine (five-fold difference in cardiovascular mortality between the lowest and the highest creatinine strata). The risk associated with renal insufficiency was independent of other classic cardiovascular risk factors. Two trials of hypertensives with low risk (HOT and a small Italian trial) found that cardiovascular outcomes approximately doubled in subjects with MRI. Another study (MRFIT) found that it was not baseline creatinine, but its increase on follow-up that predicted future cardiovascular disease. These observational data suggest that regardless of etiology MRI is a strong predictor of cardiovascular disease and is found in 10% of populations at low cardiovascular risk and in up to 30% of those at high risk. No prospective therapeutic trials aimed at reducing the cardiovascular burden in people with MRI are available. Subgroup analyses of the HOPE study indicate that angiotensin-converting enzyme (ACE) inhibition with ramipril is beneficial and does not increase the risk of such side effects as acute renal failure or hyperkalemia. Thus the frequent practice of withholding ACE inhibitors from patients with mild renal insufficiency is unwarranted, especially since MRI identifies a group at high risk that appears to benefit most from treatment. Moreover, there is evidence that ACE inhibitors improve renal outcomes in renal insufficiency. Prospective studies should test the predictive power of early renal insufficiency for cardiovascular disease and prognosis with various therapeutic options.

Age Factors↗

Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials.

CONTEXT: Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. OBJECTIVE: To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. DATA SOURCES AND STUDY SELECTION: MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. DATA EXTRACTION: Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding). DATA SYNTHESIS: Among 51,342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44,114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). CONCLUSIONS: For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.

Aspirin↗

Cardiovascular risk in patients with mild renal insufficiency.

We reviewed the evidence linking mild renal insufficiency (MRI) to an increased cardiovascular risk. A number of cardiovascular risk factors become prevalent with MRI, including night-time hypertension, increase in lipoprotein(a), in homocysteine, in asymmetric dimethyl-arginine (ADMA), markers and mediators of inflammation, and insulin resistance. Also, an epidemiologic association between coronary artery disease and nephrosclerosis, a frequent cause of mild renal insufficiency in the elderly, is documented. In the middle-aged, general population MRI, found in 8% of women and 9% of men, was not associated with cardiovascular disease. However, in a representative sample of middle-aged British men, the risk of stroke was 60% higher for the subgroup of people with MRI; in people at high cardiovascular risk (mostly coronary disease), the HOPE study found a 2-fold (unadjusted), or 1.4-fold (adjusted), higher incidence of cardiovascular outcomes with MRI. The incidence of primary outcome increased with the level of serum creatinine. Several studies determined the cardiovascular risk associated with MRI in hypertension. In HDFP, as in HOPE, cardiovascular mortality increased with higher serum creatinine (five-fold difference in cardiovascular mortality between the lowest and the highest creatinine strata). The risk associated with renal insufficiency was independent from other classic cardiovascular risk factors. In hypertensives with low risk, the HOT, and a small Italian trial found about a doubling in cardiovascular outcomes in MRI. However, in MRFIT, increase in follow-up creatinine predicted future cardiovascular disease, not baseline creatinine. These observational data suggest that MRI, independent of etiology, is a strong predictor of cardiovascular disease, present in 10% of a population at low risk, and up to 30% at high cardiovascular risk. No prospective therapeutic trials, aimed at reducing the cardiovascular burden in people with MRI, are available. Subgroup analyses of the HOPE study indicate that ACE inhibition with ramipril is beneficial without an increased risk for side effects like acute renal failure or hyperkalemia. Thus, the frequent practice of withholding ACE inhibitors from patients with mild renal insufficiency is unwarranted, especially since this identifies a group at high risk that appears to benefit most from treatment. In addition, there is evidence that ACE inhibitors improve renal outcomes in renal insufficiency. Prospective studies should test the predictive power of MRI for cardiovascular disease and therapeutic options.

Cardiovascular Diseases↗

Gout, just a nasty event or a cardiovascular signal? A study from primary care.

OBJECTIVE: Our aim was to examine the relationship between gout on the one hand and cardiovascular diseases and cardiovascular risk indicators on the other. METHODS: A case-control study was carried out in an aggregate primary care population of approximately 12 000 patients from four Dutch general practices, with follow-up of the cases free of cardiovascular diseases at the time of the first registered episode of gout. The subjects comprised 261 patients with a first episode of gout, 170 of whom were without prevalent cardiovascular diseases, and two control patients for each case matched for age, sex and practice. In the case-control study, the main outcome measures were the prevalence of cardiovascular morbidity (angina pectoris, myocardial infarction, heart failure, cerebrovascular accident, transient ischaemic attack, peripheral vascular disease), hypertension, diabetes mellitus, obesity and hypercholesterolaemia; in the follow-up study, the main outcome measure was the incidence of cardiovascular morbidity. RESULTS: Thirty-five percent of 261 gout patients and 26% of 522 controls had one or more prevalent cardiovascular diseases. Compared with controls, patients had a higher prevalence of hypertension (43% versus 18%), hypercholesterolaemia (14% versus 6%) and obesity (56% versus 30%). A total of 170 gout patients without prevalent cardiovascular diseases (compared with 340 controls) had a higher prevalence of hypertension (39% versus 14%), hypercholesterolaemia (8% versus 4%), diabetes mellitus (5% versus 1%) and obesity (52% versus 27%). The first occurrence of a cardiovascular disease (real end-point) was seen in 26% of the patients free of cardiovascular morbidity and in 21% of the controls. This difference was not significant. In a Cox proportional hazard model, controlling for the cardiovascular risk indicators, gout did not prove to be an independent determinant for the development of cardiovascular disease. CONCLUSION: Gout was found to be associated with cardiovascular diseases and with cardiovascular risk indicators, without evidence of it being an independent risk indicator itself. A gout attack should be an incentive to assess the cardiovascular risk profile, when a patient seeks medical help.

Adolescent↗

Evidence for increased cardiovascular disease risk in patients with chronic kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease is becoming recognized as an important risk factor for cardiovascular disease. Recent publications on cardiovascular disease risk in chronic kidney disease, cardiovascular disease risk factors in chronic kidney disease and clinical trials for cardiovascular disease risk reduction in chronic kidney disease are summarized. RECENT FINDINGS: An American Heart Association statement published in 2003 recommended that patients with chronic kidney disease be considered as members of the 'highest risk group' for subsequent cardiovascular disease events. In the past year, several large prospective studies have reported that cardiovascular disease risk is independently associated with chronic kidney disease markers, e.g. elevated serum creatinine, low estimated glomerular filtration rate and microalbuminuria. The populations studied have included community samples of middle-aged and older adults, subjects with myocardial infarction, those undergoing coronary angiography, and transplant patients. There is a very strong crude association between a low glomerular filtration rate and cardiovascular disease and mortality. Much of the association is explained by traditional cardiovascular disease risk factors, but an independent risk remains. Studies have documented a disturbing underutilization of preventive treatments for cardiovascular disease among patients with chronic kidney disease. Studies of non-traditional cardiovascular disease risk factors are reviewed. The utility of targeting these for cardiovascular disease risk reduction needs to be proved. A summary of large ongoing clinical trials intended to reduce cardiovascular disease risk in chronic kidney disease is presented. SUMMARY: Increasing data support the importance of chronic kidney disease as a predictor of cardiovascular disease risk. However, treatments designed to lower cardiovascular disease risk are used less often in patients with chronic kidney disease than in patients without chronic kidney disease. There is a need for increased application and testing of cardiovascular disease prevention treatments in chronic kidney disease.

Aging↗

Cardiovascular risk in patients with early renal insufficiency: implications for the use of ACE inhibitors.

Patients with end-stage renal disease die from cardiovascular disease at a much younger age than people in the general population do. Here, we review the evidence linking early renal insufficiency (ERI) to an increased cardiovascular risk. A number of cardiovascular risk factors become prevalent with ERI, including night-time hypertension, increase in serum levels of lipoprotein (a), homocysteine and asymmetric dimethyl-arginine, and insulin resistance. Also, an epidemiologic association between coronary artery disease (CAD) and nephrosclerosis, a frequent cause of ERI in the elderly, is documented. In the middle-aged, general population ERI, found in 8% of women and 9% of men, was not associated with cardiovascular disease. However, in a representative sample of middle-aged British men the risk of stroke was 60% higher for the subgroup of individuals with ERI. In people at high cardiovascular risk (mostly CAD), the Heart Outcomes Prevention Evaluation (HOPE) study found a 2-fold (unadjusted) or 1.4-fold (adjusted) higher incidence of cardiovascular outcomes with ERI. The incidence of primary outcome increased with the level of serum creatinine. At least four studies have determined the cardiovascular risk associated with ERI in hypertension. In Hypertension Detection and Follow-up Program, as in HOPE, cardiovascular mortality increased with higher serum creatinine levels (5-fold difference in cardiovascular mortality between the lowest and the highest creatinine strata). In patients with hypertension with low risk, the Hypertension Optimal Treatment and a small Italian trial found about a doubling in cardiovascular outcomes in ERI. However, in the Multiple Risk Factor Intervention Trial, not baseline serum creatinine level, but its increase on follow-up predicted future cardiovascular disease. These observational data suggest that ERI, independent of etiology, is a strong predictor of cardiovascular disease, present in 10% of a population at low, and up to 30% at high, cardiovascular risk. No prospective therapeutic trials aimed at reducing the cardiovascular burden in individuals with ERI are available. Subgroup analyses of the HOPE study indicate that ACE inhibition with ramipril is beneficial without an increased risk of adverse effects like acute renal failure or hyperkalemia. Thus the frequent practice of withholding ACE inhibitors from patients with mild renal insufficiency is unwarranted, especially since this identifies a group at high risk who appears to benefit most from treatment. In addition, there is evidence that ACE inhibitors improve renal outcomes in renal insufficiency. Prospective studies should test the predictive power of ERI for cardiovascular disease and therapeutic options.

Angiotensin-Converting Enzyme Inhibitors↗

Task Force 4: The relationship between cardiovascular specialists and generalists.

1. An imbalance between generalists and cardiovascular subspecialists exists that will require decades to correct. We question the validity of the 50:50 generalist/specialist ratio in view of current practice patterns for cardiology. 2. There has been a large increase in the number of cardiovascular specialists in the past 30 years that will continue if training programs remain at their current size. 3. Cardiovascular specialists provide a substantial amount of inpatient care, care to older patients and care to those with cardiovascular symptoms, although generalists actually provide the majority of office-based cardiovascular care. 4. A significant portion of cardiovascular specialist care can be classified as comprehensive care to patients with and without cardiovascular disease. 5. Most generalists and cardiovascular specialists do not perceive a need for additional cardiovascular specialists. 6. Many providers perform cardiovascular procedures at levels below the recommended threshold for maintenance of clinical competence. 7. Managed care may result in a reduced demand for cardiovascular specialists. 8. If cardiovascular specialists provide general care, it may not be assumed that previous training prepares them for generalist practice. 9. The appropriate boundaries of cardiovascular care between generalists and cardiovascular specialists are indistinct. They are defined somewhat by the training programs from which the generalists graduate. 10. Many generalists have deficiencies in basic skills in clinical cardiology. 11. Desirable interactions between generalists and cardiovascular specialists involve referral of patients in both directions to the provider who can give care to a given patient, at a given time, with the best outcome and lowest cost.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiology↗

Metabolic control and prevalent cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM): The NIDDM Patient Outcome Research Team.

PURPOSE: Cardiovascular disease is a major cause of morbidity and death in non-insulin-dependent diabetes mellitus (NIDDM). While hyperglycemia is clearly related to diabetic microvascular complications, it contribution to large-vessel atherosclerosis is controversial. PATIENTS AND METHODS: We performed an analysis of the association between glycemic control and prevalent cardiovascular disease in 1,539 participants in the NIDDM Patient Outcomes Research Team study who were under usual care in a health maintenance organization. Prevalent cardiovascular disease and its risk factors were identified by self-administered questionnaire. Cardiovascular disease was defined by the presence of coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease. Glycohemoglobin and lipid levels were obtained from a computerized laboratory database. RESULTS: The mean age of participants was 63 years (range 31 to 91); 51% were women. The mean duration of NIDDM was 9 years (range < 1 to 50), 35% took insulin, and 48% took sulfonylureas. Mean glycohemoglobin was 10.6%. Sixty percent had hypertension, 16% currently smoked cigarettes, and the mean total high-density lipoprotein (HDL) cholesterol ratio was 5.7. Fifty-one percent had cardiovascular disease. Cardiovascular disease prevalence remained constant across increasing quartiles of glycohemoglobin for both men and women. In contrast, prevalent cardiovascular disease was associated with established cardiovascular disease risk factors including age (67 versus 59 years, P < 0.0001), hypertension (66% versus 54%, P < 0.0001), current cigarette smoking (17% versus 13%, P < 0.005), and total/HDL cholesterol ratio (5.9 versus 5.6, P < 0.005). Cardiovascular disease was also associated with duration of NIDDM (11 versus 8 years, P < 0.0001). In multiple logistic regression analysis controlling for established cardiovascular disease risk factors and diabetes duration and therapy, glycohemoglobin remained unassociated with cardiovascular disease. CONCLUSIONS: Glycemic control is not associated with prevalent cardiovascular disease in this large population of individuals with NIDDM. Conventional cardiovascular disease risk factors are independently associated with cardiovascular disease and be a more promising focus for clinical intervention to reduce atherosclerotic complications in NIDDM.

Adult↗

Changes in risk factors and the decline in mortality from cardiovascular disease. The Framingham Heart Study.

A decline in mortality from cardiovascular disease over the past 30 years has been well documented, but the reasons for the decline remain unclear. We analyzed the 10-year incidence of cardiovascular disease and death from cardiovascular disease in three groups of men who were 50 to 59 years old at base line in 1950, 1960, and 1970 (the 1950, 1960, and 1970 cohorts) in order to determine the contribution of secular trends in the incidence of cardiovascular disease, risk factors, and medical care to the decline in mortality. The 10-year cumulative mortality from cardiovascular disease in the 1970 cohort was 43 percent less than that in the 1950 cohort and 37 percent less than that in the 1960 cohort (P = 0.04 by log-rank test). Among the men who were free of cardiovascular disease at base line, the 10-year cumulative incidence of cardiovascular disease declined approximately 19 percent, from 190 per 1000 in the 1950 cohort to 154 per 1000 in the 1970 cohort (0.10 less than P less than 0.20 by chi-square test), whereas the 10-year rate of death from cardiovascular disease declined 60 percent (relative risk for the 1950 cohort as compared with the 1970 cohort, 2.53; 95 percent confidence interval, 1.22 to 5.97). Significant improvements were found in risk factors for cardiovascular disease among the men initially free of cardiovascular disease in the 1970 cohort as compared with those in the 1950 cohort, including a lower serum cholesterol level (mean +/- SD, 5.72 +/- 0.98 mmol per liter [221 +/- 38 mg per deciliter], as compared with 5.90 +/- 1.03 mmol per liter [228 +/- 40 mg per deciliter]) and a lower systolic blood pressure (mean +/- SD, 135 +/- 19 mm Hg, as compared with 139 +/- 25 mm Hg), better management of hypertension (22 percent vs. 0 percent were receiving antihypertensive medication), and reduced cigarette smoking (34 percent vs. 56 percent). We propose that these improvements may have had more pronounced effects on mortality from cardiovascular disease than on the incidence of cardiovascular disease in this population. Our data suggest that the improvement in cardiovascular risk factors in the 1970 cohort may have been an important contributor to the 60 percent decline in mortality in that group as compared with the 1950 cohort, although a decline in the incidence of cardiovascular disease and improved medical interventions may also have contributed to the decline in mortality.

Blood Pressure↗

Gait disorders are associated with non-cardiovascular falls in elderly people: a preliminary study.

BACKGROUND: The association between unexplained falls and cardiovascular causes is increasingly recognized. Neurally mediated cardiovascular disorders and hypotensive syndromes are found in almost 20 percent of the patients with unexplained falls. However, the approach to these patients remains unclear. Gait assessment might be an interesting approach to these patients as clinical observations suggests that those with cardiovascular or hypotensive causes may not manifest obvious gait alterations. Our primary objective is to analyze the association between gait disorders and a non-cardiovascular cause of falls in patients with unexplained falls. A second objective is to test the sensitivity and specificity of a gait assessment approach for detecting non-cardiovascular causes when compared with intrinsic-extrinsic classification. METHODS: Cross-sectional study performed in a falls clinic at a university hospital in 41 ambulatory elderly participants with unexplained falls. Neurally mediated cardiovascular conditions, neurological diseases, gait and balance problems were assessed. Gait disorder was defined as a gait velocity < 0.8 m/s or Tinetti Gait Score < 9. An attributable etiology of the fall was determined in each participant. Comparisons between the gait assessment approach and the attributable etiology regarding a neurally mediated cardiovascular cause were performed. Fisher exact test was used to test the association hypothesis. Sensitivity and specificity of gait assessment approach and intrinsic-extrinsic classification to detect a non-cardiovascular mediated fall was calculated with 95% confidence intervals (CI95%). RESULTS: A cardiovascular etiology (orthostatic and postprandial hypotension, vasovagal syndrome and carotid sinus hypersensitivity) was identified in 14% of participants (6/41). Of 35 patients with a gait disorder, 34 had a non-cardiovascular etiology of fall; whereas in 5 out of 6 patients without a gait disorder, a cardiovascular diagnosis was identified (p < 0.001). Sensitivity and specificity of the presence of gait disorder for identifying a non-cardiovascular mediated cause was 97.1% (CI95% = 85-99) and 83% (CI95% = 36-99), respectively. CONCLUSION: In community dwelling older persons with unexplained falls, gait disorders were associated with non-cardiovascular diagnosis of falls. Gait assessment was a useful approach for the detection of a non-cardiovascular mediated cause of falls, providing additional value to this assessment.

Accidental Falls↗

Prevention of cardiovascular events in elderly people.

BACKGROUND AND OBJECTIVE: Cardiovascular disease has been identified as the leading cause of morbidity and mortality in developed countries. Given the increase in life expectancy and the development of cardiovascular preventive measures, it has become increasingly important to detect and prevent cardiovascular diseases in the elderly. We reviewed the scientific literature concerning cardiovascular prevention to assess the importance of cardiovascular preventive measures in old (> or =65 years of age) individuals. METHODS: We undertook a systematic search for references relating to prevention of cardiovascular disease in the elderly, mainly ischaemic stroke, coronary artery disease and heart failure, on the MEDLINE database 1962-2005. For cardiovascular prevention by drugs or surgery, emphasis was placed on randomised controlled trials, review articles and meta-analyses. For cardiovascular prevention by lifestyle modification, major cohort studies were also considered. RESULTS: Stroke, coronary heart disease and heart failure were found to be the main targets for cardiovascular prevention in published studies. Antihypertensive treatment has proven its efficacy in primary prevention of fatal or nonfatal stroke in hypertensive and high-risk patients >60 years of age, particularly through treatment of systolic hypertension. Systolic blood pressure reduction is equally important in the secondary prevention of stroke. Similarly, in nonvalvular atrial fibrillation, an adjusted dose of warfarin with a target International Normalized Ratio (INR) of between 2 to 3 prevents ischaemic stroke in elderly patients with an acceptable haemorrhagic risk but is still under prescribed. Antiplatelet agents are indicated in elderly patients with nonembolic strokes. Few large-scale studies have investigated the effect of HMG-CoA reductase inhibitors (statins) on stroke prevention in old individuals. To date, the largest trials suggest a beneficial effect for stroke prevention with use of statins in high-risk elderly subjects < or =82 years of age. Carotid endarterectomy is indicated in carotid artery stenosis >70% and outcomes are even better in elderly than in younger patients. However, medical treatment is still the first-line treatment in asymptomatic elderly patients with <70% stenosis. In ischaemic heart disease, different trials in elderly individuals have shown that use of statins, antithrombotic agents, beta-adrenoceptor antagonists and ACE inhibitors plays an important role either in primary or in secondary cardiovascular prevention. Hormone replacement therapy has been used to treat climacteric symptoms and postmenopausal osteoporosis and was thought to confer a cardiovascular protection. However, controlled trials in elderly individuals changed this false belief when it was found that there was no benefit and even a harmful cardiovascular effect during the first year of treatment. Smoking cessation, regular physical activity and healthy diet are, as in younger individuals, appropriate and effective measures for preventing cardiovascular events in the elderly. Finally, antihypertensive treatment and influenza vaccination are useful for heart failure prevention in elderly individuals. CONCLUSIONS: Cardiovascular prevention should be more widely implemented in the elderly, including individuals aged > or =75 years, and this might contribute to improved healthy status and quality of life in this growing population.

Aged↗

[Dolichoarteriopathy (kinking, coiling,tortuosity) of the carotid arteries and cardiovascular risk factors].

BACKGROUND AND AIMS: The clinical significance of dolichoarteriopathies (kinking, coiling, tortuosity) and their prognosis have not yet been clearly defined. A study was performed in outpatients in order to evaluate the cardiovascular risk factors of dolichoarteriopathies. METHODS: A total of 1220 subjects (620 males and 600 females, aged between 25 and 89 years old) were examined using color Doppler ultrasonography of the extracranial carotid arteries with an Acuson 128 XP-5 scan and 7 MHz linear probe. The reason for the test was the presence of clinical symptoms or cardiovascular risk factors. The risk factors studied included: arterial hypertension [systolic (> 140 mmHg) and/or diastolic arterial pressure (> 90 mmHg)], hypercholesterolemia (total cholesterol > 200 mg/dl), diabetes mellitus, cigarette smoking. Patients were divided as follows: patients with arterial hypertension alone, patients with arterial hypertension associated with other cardiovascular risk factors (hypercholesterolemia, diabetes mellitus, smoking), patients with other cardiovascular risk factors (hypercholesterolemia, diabetes mellitus, smoking), patients without risk factors. RESULTS: In 316 (25.9%) patients with dolichoarteriopathies, arterial hypertension alone was present in 98 (31%), arterial hypertension associated with other cardiovascular risk factors in 85 (26.3%) and other cardiovascular risk factors in 54 (17%), whereas 75 (25%) did not present cardiovascular risk factors. In the 904 subjects without dolichoarteriopathies, arterial hypertension alone was present in 254 (28%), arterial hypertension associated with other cardiovascular risk factors in 213 (23.6%) and other cardiovascular risk factors in 191 (21.1%), whereas 241 (27.2%) did not present cardiovascular risk factors. In 316 subjects with dolichoarteriopathies, cardiovascular risk factors were equally present in the two sexes without statistically significant differences. In cases with kinking and tortuosity, cardiovascular risk factors were equally present in the two sexes, whereas colling was more frequently associated with arterial hypertension alone in males and with arterial hypertension associated with other risk factors in females, showing a statistically significant difference. CONCLUSIONS: The findings of this study reveal that the presence of risk factors in patients with dolichoarteriopathies is comparable to that in subjects without dolichoarteriopathies. Also in the three types of dolichoarteriopathies (kinking, coiling and tortuosity), cardiovascular risk factors were equally present. Therefore, these results appear to lay the role of arterial hypertension or other cardiovascular risk factors in the genesis of diolichoarteriopathies open to question.

Adult↗

Cardiovascular disease risk status in elderly persons with renal insufficiency.

BACKGROUND: Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency. METHODS: This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors. RESULTS: Among the 5808 participants with creatinine levels measured at entry, 15.9% of men (N = 394), and 7.6% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64% in persons with renal insufficiency compared with 43% in those without it [odds ratio (OR) 2.34; 95% confidence interval (95% CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95% CI, 1.18, 1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk>20% by the Framingham equations, 78% of men and 61% of women with renal insufficiency had elevated cardiovascular risk status. CONCLUSIONS: Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults.

Age Distribution↗

Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects.

The purpose of the present study was to examine 10-year cardiovascular morbidity and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic control subjects and to evaluate the effects of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia in diabetic patients on cardiovascular mortality. Furthermore, the extent to which the above-mentioned factors could contribute to the excessive cardiovascular mortality observed in diabetic patients was examined. In the years 1979-1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2 diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45-64 years were studied. Both groups were re-examined in the years 1985-1986 and 1991-1992. The impact of different factors on cardiovascular mortality was examined by univariate analyses after adjustment for age and sex and by multiple logistic regression analyses. The age-standardized total and cardiovascular mortality rates were substantially higher in diabetic men (17.8 and 15.0%, total and cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and 16.6%, p < 0.01 for both) than in non-diabetic control men (5.2% both total and cardiovascular mortality) and women (4.2 and 2.2%). Cardiovascular mortality was not related to the treatment modality (diet, oral drugs, insulin) at 5 years from diagnosis. Use of diuretics, beta-blocking agents or their combination at baseline did not make a significant contribution to cardiovascular mortality either. In multiple logistic regression analysis on diabetic patients, age, LDL triglycerides, smoking, blood glucose and ischaemic ECG at baseline had independent associations with cardiovascular mortality. Interestingly, urinary albumin excretion rate measured at 5-year examination also predicted 10-year cardiovascular mortality after adjustment for the effects of major risk factors including lipoprotein abnormalities, but its predictive power reduced to a nonsignificant level when the effect of plasma glucose was taken into account. The relative risk of cardiovascular mortality associated with diabetes was 8.2 after allowing for age alone, but it declined to 3.7 when all contributing factors from the baseline examination (except blood glucose) were taken into account. In conclusion, the present results indicate that LDL triglycerides and/or other changes in lipoprotein composition characteristic of Type 2 diabetes and manifesting as elevated serum triglycerides are atherogenic and they strongly predict increased cardiovascular mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗