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Biomedical subjects

Gorm Jensen

Publications and source records attributed to Gorm Jensen.

At least 19 recordsLinked to original sources

Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial.

OBJECTIVES: To evaluate the long term effects of perioperative beta blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. DESIGN: Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. SETTING: University anaesthesia and surgical centres and one coordinating centre. PARTICIPANTS: 921 patients aged > 39 scheduled for major non-cardiac surgery. INTERVENTIONS: 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. MAIN OUTCOME MEASURES: The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. RESULTS: Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (- 0.8% to 5.6%). CONCLUSIONS: Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58485613.

Adrenergic beta-Antagonists↗

Fibrinogen and albumin levels and risk of atrial fibrillation in men and women (the Copenhagen City Heart Study).

Cross-sectional and limited prospective evidence has suggested that inflammatory markers may predict for the risk of atrial fibrillation (AF). In a prospective cohort study, we studied the risk of incident AF among 8,870 women and men free of cardiovascular disease enrolled in the Copenhagen City Heart Study. We measured plasma fibrinogen and serum albumin levels at a study visit from 1991 to 1994. We identified 286 subsequent cases of AF during a mean of 7.5 years of follow-up by a validated nationwide registry of all hospitalizations. The fibrinogen levels at baseline were associated with a higher risk of AF, with a multivariate-adjusted hazard ratio for the highest versus lowest quartiles of 1.98 (95% confidence interval [CI] 0.94 to 4.17) among men and 2.14 (95% CI 1.15 to 3.96) among women. The albumin levels were inversely associated with the risk of AF among women (hazard ratio 0.47, 95% CI 0.28 to 0.77) but not among men (hazard ratio 1.01, 95% CI 0.56 to 1.84). Additional adjustment for cases of coronary heart disease, congestive heart failure, and stroke that occurred during follow-up did not attenuate these associations. In conclusion, higher levels of fibrinogen and lower levels of albumin were prospectively associated with a higher risk of AF, even accounting for their relation with the risk of cardiovascular disease. These findings support the hypothesis that inflammation contributes to the etiology of AF.

Aged↗

Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study.

BACKGROUND: The relationship of the full range of alcohol consumption with risk of incident atrial fibrillation has been inconsistent in previous, mainly case-control studies. METHODS AND RESULTS: In a prospective cohort study, we studied the association between self-reported alcohol use and incident atrial fibrillation among 16,415 women and men enrolled in the Copenhagen City Heart Study. We ascertained use of beer, wine, and spirits individually at up to 3 study visits with a structured questionnaire. We identified cases of atrial fibrillation by routine study ECGs and a validated nationwide registry of all hospitalizations. A total of 1071 cases occurred during follow-up. Among both women and men, alcohol consumption throughout the moderate range was not associated with risk of atrial fibrillation. However, consumption of 35 or more drinks per week among men was associated with a hazard ratio of 1.45 (95% CI 1.02 to 2.04); few women consumed this amount of alcohol. Approximately 5% of cases of atrial fibrillation among men were attributable to heavy alcohol use. Further adjustment for blood pressure and incident coronary heart disease and congestive heart failure did not attenuate the association (hazard ratio 1.63; 95% CI 1.15 to 2.31). CONCLUSIONS: Heavy alcohol consumption is associated with a higher risk of atrial fibrillation, at least among men. This relationship does not appear to be related to the adverse effects of heavy drinking on coronary heart disease or blood pressure.

Alcohol Drinking↗

Relation of 97T polymorphism in KCNE5 to risk of atrial fibrillation.

The 97T polymorphism of the KCNE5 gene, coding for an inhibitory beta-subunit, MiRP4, of the repolarizing cardiac potassium ion channel KCNQ1, was significantly more frequent in 96 controls than in 158 patients with atrial fibrillation (AF). KCNQ1 is involved in cardiac action potential, and increased function has been associated with AF. Because the KCNE5 gene is located on the X chromosome, the protection conferred by the 97T polymorphism may help explain the gender-related difference in the risk of AF.

Adult↗

New definition of microalbuminuria in hypertensive subjects: association with incident coronary heart disease and death.

Microalbuminuria has so far been defined as urinary albumin excretion between 20 and 200 microg/min (or 15 to 150 microg/min overnight). In a recent report, an overnight urinary albumin excretion >5 microg/min was strongly predictive of coronary heart disease and death in the general population. The aim of the present study was to confirm this observation in a population of hypertensive individuals. In The Third Copenhagen City Heart Study in 1992 to 1994, 1734 men and women aged 30 to 70 years with hypertension, but no history of coronary heat disease, delivered a timed overnight urine sample. They were followed-up prospectively by registers until 2000 with respect to coronary heart disease, and until 2004 with respect to death. During follow-up, 123 incident cases of coronary heart disease and 308 deaths were traced. Incident coronary heart disease occurred in 11% of subjects with urinary albumin excretion > or =5 microg/min compared with 5% in subjects with urinary albumin excretion <5 microg/min (P<0.001). Similarly, the cumulative mortality was 28% versus 13% (P<0.001). The relative risks of coronary heart disease and death associated with urinary albumin excretion > or =5 microg/min were 2.0 (1.4 to 2.9; P<0.001) and 1.9 (1.5 to 2.3; P<0.001), respectively, after adjustment for age, sex, blood pressure level, antihypertensive drugs, diabetes, creatinine clearance, smoking, lipoproteins, and body mass index. In conclusion, our study supports the new definition of microalbuminuria as urinary albumin excretion >5 microg/min. In future risk assessment in hypertensive individuals, measurement of microalbuminuria has to be included.

Adult↗

Social network diversity and risks of ischemic heart disease and total mortality: findings from the Copenhagen City Heart Study.

Measures of various types of social contacts were used as predictors of ischemic heart disease events and total mortality in an age-stratified random sample of 9,573 adults enrolled in the Copenhagen City Heart Study (Copenhagen, Denmark). Baseline examinations were conducted in 1991-1994, and participants were followed until the end of 1997. Contacts with parents, children, family members, and friends were associated with better health. The presence of a spouse or partner was protective for men. Contacts with neighbors showed a trend toward a reversed pattern, and the effects of contacts with work colleagues and children differed by gender. Most types of contacts that occurred at least monthly were just as protective as those occurring more frequently. An index of intimate social contact diversity with family and friends had graded relations with both outcomes. Comparisons of persons reporting three or more types of contacts with those reporting fewer types yielded age- and gender-adjusted hazard ratios of 0.73 (95% confidence interval (CI): 0.64, 0.82) for mortality and 0.75 (95% CI: 0.61, 0.91) for ischemic heart disease. Comparable fully adjusted hazard ratios were 0.83 (95% CI: 0.73, 0.95) and 0.82 (95% CI: 0.67, 1.00). These data suggest that health benefits are derived from the diversity of social roles, especially those involving intimate relationships.

Adult↗

The influence of duration of follow-up on the association between alcohol and cause-specific mortality in a prospective cohort study.

PURPOSE: To investigate whether duration of follow-up influences the association between alcohol and cause-specific mortality in a prospective cohort study with only baseline assessment of alcohol intake. METHODS: In a cohort of 14,223 men and women participating in the first investigation of the Copenhagen City Heart Study between 1976 and 1978 and followed until 2001, we assessed whether the association between alcohol and mortality was modified by duration of follow-up. The 24 years of follow-up were divided into four intervals, and Cox survival analyses were conducted separately for these four succeeding 6-year periods of follow-up. RESULTS: The authors found differences in the predictive values of alcohol and beverage-specific types of alcohol depending on duration of follow-up both in terms of all-cause mortality and death from coronary heart disease and cancer. The apparent protective effect of a moderate alcohol consumption on coronary heart disease attenuated during prolonged follow-up, whereas high alcohol consumption became associated with higher risk of death from cancer with longer follow-up. CONCLUSIONS: This study accentuates the importance of taking duration of follow-up into consideration when interpreting risk estimates from prospective studies on the association between alcohol and mortality.

Adult↗

The effects of a randomised multi-centre trial and international accreditation on availability and quality of clinical guidelines.

PURPOSE: To examine the availability and quality of clinical guidelines on perioperative diabetes care in hospital units before and after a randomised clinical trial (RCT) and international accreditation. DESIGN/METHODOLOGY/APPROACH: Interventional "before-after" study in 51 units (38 surgical and 13 anaesthetic) in nine hospitals participating in a RCT in the greater Copenhagen area; 27 of the units also underwent international accreditation. FINDINGS: The proportion of units with guidelines increased from 24/51 (47 percent) units before to 38/51 (75 percent) units after the trial. Among the 27 units without guidelines before the trial, significantly more accredited units compared to non-accredited units had a guideline after the trial (9/10 (90 percent) compared to 5/17 (29 percent). The quality of the systematic development scale and the clinical scales improved significantly after the trial in both accredited units (both p < 0.001) and in non-accredited units (both p < 0.02). The improvement of the systematic development scale was significantly higher in accredited than in non-accredited units (p < 0.01). ORIGINALITY/VALUE: The combination of conducting both the DIPOM Trial and international accreditation led to a significant improvement of both dissemination and quality of guidelines on perioperative diabetic care.

Accreditation↗

Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations.

BACKGROUND: The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population and type of mutation (LDL receptor [LDLR] or APOB R3500Q) for cholesterol phenotype. METHODS AND RESULTS: We studied 9255 individuals from the general population, 948 patients with ischemic heart disease (IHD), and 63 patients with clinical familial hypercholesterolemia (FH) for 3 common LDL receptor mutations. Average increase in cholesterol in LDL receptor heterozygotes identified in the general population or among patients with IHD or FH compared with noncarriers was 2.9 mmol/L, 4.1 mmol/L, and 4.9 mmol/L, respectively (P=0.02). Background population and type of mutation determined cholesterol phenotype; average increase in LDL cholesterol from carriers in the general population to carriers with clinical FH was 1.6 mmol/L (P=0.03). The average increase for carriers of LDLR mutations compared with carriers of APOB R3500Q was 1.2 mmol/L (P=0.05). CONCLUSIONS: The phenotype associated with a given mutation should not be determined in patients, but rather in unselected individuals in the general population.

Adolescent↗

Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.

BACKGROUND: The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association. METHODS AND RESULTS: In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 microg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P<0.001) and death (RR, 1.9; 95% CI, 1.5 to 2.4; P<0.001) independently of age, sex, renal creatinine clearance, diabetes mellitus, hypertension, and plasma lipids. Lower levels of urinary albumin excretion were not associated with increased risk. CONCLUSIONS: Microalbuminuria, defined as urinary albumin excretion >4.8 microg/min (corresponding to approximately 6.4 microg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.

Adult↗

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery.

BACKGROUND: Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative beta-blockade. METHODS: The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive, >or=40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months. RESULTS: Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both. CONCLUSION: The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.

Adrenergic beta-Antagonists↗

Decreasing population blood pressure: 15 years of follow-up in the Copenhagen City Heart Study (CCHS).

OBJECTIVE: Population blood pressure (BP) levels from a longitudinal study were analysed for trends during a period of 15 years. Trends from unadjusted data are reported as well as trends adjusted for major cardiovascular (CV) risk factors and use of antihypertensive therapy, thus allowing assessment of independent BP trends. DESIGN: The Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random population sample of both genders aged 20 and above. Three cross-sectional population surveys were performed: 1976-78 (n=14000), 1981-83 (n=12675) and 1991-94 (n=9661). METHODS: BP was measured by a London School of Hygiene Sphygmomanometer. Weight and height were measured and body mass index (BMI) calculated. Non-fasting plasma cholesterol was determined. A questionnaire concerning smoking status and diabetes was completed. Measurement methods were strictly standardized and unchanged in the three cross-sectional surveys. RESULTS: Unadjusted systolic BP (SBP) levels decreased during 15 years of follow-up, and unadjusted diastolic BP (DBP) levels increased. An investigation of the effect of major CV risk factors, both singly and jointly on BP levels, revealed a pattern of correlations contributing to BP variability. Adjustments for BMI, cholesterol, diabetes, use of antihypertensive therapy and smoking status were made in the final analyses of BP trend. The adjusted trend model demonstrated that SBP levels remained lower than SBP levels in the first survey. DBP levels increased slightly. CONCLUSIONS: The results demonstrate a decrease in population SBP. The decrease is independent of major CV risk factors. Possible contributing factors are discussed.

Adult↗

Changes in alcohol intake and mortality: a longitudinal population-based study.

BACKGROUND: Using alcohol intake at one point in time, numerous studies have shown a J- or U-shaped relation with all-cause mortality. Mortality is lowest among the light to moderate drinkers, with the risk of dying from coronary heart disease higher among nondrinkers and the risk of dying from cancer higher among heavy drinkers. We studied whether changes in individual alcohol intake result in corresponding changes in mortality. METHODS: In a longitudinal study of 6644 men and 8010 women, age 25 to 98 years, who had attended at least 2 health surveys with a 5-year interval between them, we addressed the risk of death after combinations of changes in alcohol intake. RESULTS: Mortality after changes in alcohol intake was consistent with the mortality observed among those who reported stable drinking. Stable drinkers showed a U-shaped all-cause mortality, with relative risks of 1.29 (95% confidence interval [CI] = 1.13-1.48) for nondrinkers (< 1 drink per week) and 1.32 (1.15-1.53) for heavy drinkers (> 13 drinks per week) compared with light drinkers (1 to 6 drinks per week). For coronary heart disease mortality, stable nondrinkers had a relative risk of 1.32 (0.97-1.79) compared with stable light drinkers and those who had reduced their drinking from light to none increased their risk (1.40; 1.00-1.95), and those who had increased from nondrinking to light drinking reduced their relative risk ratio (0.71; 0.44-1.14). Cancer mortality was increased in all groups of heavy drinkers. CONCLUSION: Persons with stable patterns of light and moderate alcohol intake had the lowest all-cause mortality. Individual changes in alcohol intake were followed by corresponding changes in mortality.

Adult↗

Genetically reduced antioxidative protection and increased ischemic heart disease risk: The Copenhagen City Heart Study.

BACKGROUND: Extracellular superoxide dismutase (EC-SOD) is an antioxidative enzyme found in high concentrations in the arterial wall. Two to three percent of all people in Denmark carry an R213G substitution, which increases plasma concentration 10-fold. This may reduce arterial wall EC-SOD concentrations, increase intimal LDL oxidation, and therefore may accelerate atherogenesis. Our primary hypothesis was that EC-SOD-R213G predisposes to ischemic heart disease (IHD). The secondary hypothesis was that EC-SOD-R213G offers predictive ability with respect to IHD beyond that offered by measurements of plasma EC-SOD and autoantibodies against oxidized LDL (oxLDL). METHODS AND RESULTS: The primary hypothesis was tested in a prospective, population-based study of 9188 participants from The Copenhagen City Heart Study with 956 incident IHD events during 23 years of follow-up and retested cross-sectionally with independent case populations of patients with IHD (n=943) or ischemic cerebrovascular disease (ICVD) (n=617). Case populations were compared with unmatched IHD/ICVD-free control subjects from The Copenhagen City Heart Study (n=7992). The secondary hypothesis was tested by using a nested case-control study comparing patients with IHD (n=956) with age- and gender-matched control subjects (n=956). Age- and gender-adjusted relative risk for IHD in heterozygotes (n=221, 2.4%) versus noncarriers (n=8965, 97.6%) was 1.5 (95% CI, 1.1 to 2.1). Retesting confirmed this: Age- and gender-adjusted odds ratios for IHD was 1.4 (1.0 to 2.0) and for ICVD 1.7 (1.1 to 2.7). Additional adjustment for plasma EC-SOD produced an odds ratio for IHD in heterozygotes versus noncarriers of 9.2 (1.2 to 72), whereas adjustment for autoantibodies against oxLDL produced an odds ratio of 2.5 (1.2 to 5.3). CONCLUSIONS: Heterozygosity for EC-SOD-R213G is associated with increased IHD risk. Genotyping offers predictive ability with respect to IHD beyond that offered by plasma EC-SOD and autoantibodies against oxLDL.

Adult↗

Angiotensinogen single nucleotide polymorphisms, elevated blood pressure, and risk of cardiovascular disease.

In this study of 10 690 individuals, associations with elevated blood pressure, ischemic heart disease, and ischemic cerebrovascular disease were determined for two noncoding [A(-20)C, G(-6)A] and two coding (T174M, M235T) single nucleotide polymorphisms, analyzed alone and in combination (haplotypes). Participants from the general population with (n=4950) and without (n=4234) elevated blood pressure were compared (study 1), as were participants from the general population without ischemic heart disease and ischemic cerebrovascular disease (n=7965) and cases with either ischemic heart disease (n=1850, study 2) or ischemic cerebrovascular disease (n=848, study 3). Finally, 22-year follow-up of 9184 individuals from the general population examined risk of ischemic heart disease (study 4) and ischemic cerebrovascular disease (study 5). Individuals with -6AA, 174TT, or 235TT had plasma angiotensinogen levels increased by 80 ng/mL (P=0.01 and 0.05 for women and men) compared with individuals with -6GG, 174TT, or 235 MM. In women, this difference was associated with an odds ratio of elevated blood pressure of 1.25 (1.03 to 1.51), which increased to 1.63 (1.05 to 2.51) in postmenopausal women receiving hormone replacement therapy. The promoter single nucleotide polymorphisms alone or as haplotypes did not predict the continuous variables of systolic, diastolic, or pulse pressure in cross section or the risk of ischemic heart disease or ischemic cerebrovascular disease in either gender in case-control or prospective studies. Individuals with -6AA, 174TT, or 235TT in the angiotensinogen gene have increased plasma angiotensinogen levels and moderately increased risk of elevated blood pressure (women only) but unaltered blood pressure examined as a continuous variable and unaltered risk of ischemic heart disease and ischemic cerebrovascular disease.

Angiotensinogen↗