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Biomedical subjects

Sverre E Kjeldsen

Publications and source records attributed to Sverre E Kjeldsen.

At least 19 recordsLinked to original sources
PubMed2025

Blood Pressure Lowering and Risk of Cancer: Individual Participant-Level Data Meta-Analysis and Mendelian Randomization Studies.

BACKGROUND: Pharmacologic blood pressure (BP) lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensive agents and the risk for cancer. However, evidence from randomized controlled trials (RCTs) regarding the effect of long-term pharmacologic BP lowering on the risk for new-onset cancer is limited, with most knowledge derived from observational studies. OBJECTIVES: The aim of this study was to assess whether long-term BP lowering affects the risk for new-onset cancer, cause-specific cancer death, and selected site-specific cancers. METHODS: Individual-level data from 42 RCTs were pooled using a one-stage individual participant data meta-analysis. The primary outcome was incident cancer of all types, and secondary outcomes were cause-specific cancer death and selected site-specific cancers. Prespecified subgroup analyses were conducted to assess the heterogeneity of the BP-lowering effect by baseline variables and over follow-up time. Cox proportional hazards regression, stratified by trial, was used for the statistical analysis. For site-specific cancers, analyses were complemented with Mendelian randomization, using naturally randomized genetic variants associated with BP lowering to mimic the design of a long-term RCT. RESULTS: Data from 314,016 randomly allocated participants without known cancer at baseline were analyzed. Over a median follow-up of 4 years (Q1-Q3: 3-5 years), 17,954 participants (5.7%) developed cancer, and 4,878 (1.5%) died of cancer. In the individual participant data meta-analysis, no associations were found between reductions in systolic or diastolic BP and cancer risk (HR per 5 mm Hg reduction in systolic BP: 1.03 [95% CI: 0.99-1.06]; HR per 3 mm Hg reduction in diastolic BP: 1.03 [95% CI: 0.98-1.07]). No changes in relative risk for incident cancer were observed over follow-up time, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on cause-specific cancer death was found. For site-specific cancers, no evidence of an effect was observed, except a possible link with lung cancer risk (HR for systolic BP reduction: 1.17; 99.5% CI: 1.02-1.32). Mendelian randomization studies showed no association between systolic or diastolic BP reduction and site-specific cancers, including overall lung cancer and its subtypes. CONCLUSIONS: Randomized data analysis provided no evidence to indicate that pharmacologic BP lowering has a substantial impact, either increasing or decreasing, on the risk for incident cancer, cause-specific cancer death, or selected site-specific cancers.

epidemiology↗
PubMed2007

Prevention of new-onset atrial fibrillation and its predictors with angiotensin II-receptor blockers in the treatment of hypertension and heart failure.

Atrial fibrillation is the most frequent occurring sustained cardiac arrhythmia and it is related to common cardiac disease conditions. Hypertension increases the risk of atrial fibrillation by approximately two-fold and, because of the high prevalence of hypertension, it accounts for more cases of atrial fibrillation than any other risk factor. In recent years, there are two large hypertension trials (LIFE and VALUE) and two large heart failure trials (CHARM and Val-HeFT) reporting the beneficial effect of angiotensin II-receptor blockers (ARBs) on new-onset atrial fibrillation, beyond the blood pressure-lowering effect. Blockade of the renin-angiotensin system may prevent left atrial dilatation, atrial fibrosis, dysfunction and conduction velocity slowing. Some studies also indicate direct anti-arrhythmic properties. This review aims to consider the preventive effect of ARBs on new-onset atrial fibrillation observed in recent reports from these trials, and to discuss possible mechanisms of the beneficial effect of angiotensin II-receptor blockade.

Age Distribution↗
PubMed2006

Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension.

CONTEXT: Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear. OBJECTIVE: To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study. INTERVENTIONS: Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end. MAIN OUTCOME MEASURE: New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration). RESULTS: After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01). CONCLUSIONS: Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.

Aged↗
PubMed2006

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.

Aged↗
PubMed2006

Impact of diabetes mellitus on regression of electrocardiographic left ventricular hypertrophy and the prediction of outcome during antihypertensive therapy: the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study.

BACKGROUND: Diabetes mellitus is associated with increased cardiovascular (CV) morbidity and mortality and with greater ECG left ventricular hypertrophy (LVH); however, it is unclear whether diabetes attenuates regression of hypertensive LVH and whether regression of ECG LVH has similar prognostic value in diabetic and nondiabetic hypertensive individuals. METHODS AND RESULTS: A total of 9193 hypertensive patients (1195 with diabetes) in the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study were treated with losartan- or atenolol-based regimens and followed up with serial ECG and blood pressure determinations at baseline and 6 months and then yearly until death or study end. ECG LVH was defined with gender-adjusted Cornell voltage-duration product (CP) criteria >2440 mm . ms. After a mean follow-up of 4.8+/-0.9 years, patients with diabetes had less regression of CP LVH (-138+/-866 versus -204+/-854 mm . ms, P<0.001), remained more likely to have LVH by CP (56.0% versus 48.1%, P<0.001), and had higher rates of CV death, myocardial infarction, stroke, and all-cause mortality and of the LIFE composite end point of CV death, myocardial infarction, or stroke. In multivariable Cox proportional hazards models, in-treatment regression or absence of ECG LVH by CP was associated with between 17% and 35% reductions in event rates in patients without diabetes but did not significantly predict outcome in patients with diabetes. CONCLUSIONS: Hypertensive patients with diabetes have less regression of CP LVH in response to antihypertensive therapy than patients without diabetes, and regression of ECG LVH is less useful as a surrogate marker of outcomes in hypertensive patients with diabetes. These findings may in part explain the higher CV morbidity and mortality in hypertensive patients with diabetes, and the absence of a demonstrable improvement in prognosis in diabetic patients in response to regression of ECG LVH suggests a more complex interrelation between underlying LV structural and functional abnormalities and outcome in these patients.

Aged↗
PubMed2006

Are all the hypertensives made equal?

Blood pressure lowering in hypertensive patients is of significant importance. The complex pathophysiology makes the therapeutic targets many, and extensive research has provided us with many antihypertensive drugs. However, data indicate that the proportion of patients with controlled blood pressure is far from satisfying. This may partly be explained by a lack of individualized treatment. Present guidelines for management of hypertension emphasize that a thorough evaluation of the patient is necessary before initiating treatment. Based on information about gender, age, ethnicity, family history, clinical examination and concomitant diseases like diabetes mellitus, coronary heart disease, heart failure, cerebrovascular disease and gout, the physician is able to provide the best treatment. However, most patients need two to three drugs to control the blood pressure. Thus, we need methods to predict blood pressure responses to the various drugs in the individual patients. Possibly, in the future treatments may be based upon genetic variants. Until now, several polymorphisms in genes regulating blood pressure have been located, and these may influence responses to drugs. However, the results are heterogeneous and contradictory, and we are yet not capable of determining the best treatment based on genetic properties. Coming years challenge us to further clarify these potentially important aspects of treatment. Meanwhile, physicians are obligated to individualize the treatment by other means, based on disease history, concomitant diseases and clinical examination.

Adult↗
PubMed2006

Is there an association between severe job strain, transient rise in blood pressure and increased mortality?

BACKGROUND: Job strain may be associated with various diseases and increased mortality but there is little data available from prospective studies with long-term follow-up. OBJECTIVE: To assess the effect of heat exposure followed by severe job strain on blood pressure, heart rate and mortality. DESIGN: Prospective 19-year observational study (1982-2000) of a cohort of employees in a ferry alloy plant undergoing two economical crises. The participants were 218 healthy males aged 30-59 years. MEASUREMENTS: Annual standardized measurements of blood pressure, heart rate, serum cholesterol and registration of morbidity and mortality. RESULTS: Heat-exposed men (n = 25) and non-heat-exposed men (n = 193) had unchanged blood pressure from 1982 to 1984. Thereafter the plant underwent two serious economic crises, in 1985-87 and 1990-91, respectively. The first one was handled by decisions exclusively taken by the head office and included a gradual lay-off of 25% of the workers, and the second one was handled jointly between the local management, union leaders and employees and included a modest, voluntary lay-off. Thus, the two crises differed markedly in low vs high job control. Blood pressures gradually increased from 1985 to 1988 in the whole cohort until systolic blood pressure reached 15 mmHg and diastolic blood pressure 12 mmHg above baseline levels (p < 0.001). Thereafter blood pressures decreased to slightly above baseline levels and then remained unchanged for the next 5 years. However, heart rate increased from 62 +/- 12 beats/min in 1982-83 to 69 +/- 10 beats/min in 1988 (p < 0.01) and did not return to baseline. Total mortality by 31 December 2000 in the study cohort was significantly higher over the 19 years of follow-up than among age-matched, Norwegian men (p < 0.01). CONCLUSIONS: If a cause-effect relationship exists between the first economical crisis in the ferry alloy plant and the concomitant rise in blood pressure, job strain had a powerful but time-limited effect on blood pressure. Since the same phenomenon was not reproduced 5 years later, the marked difference in job control (high vs low) may constitute the difference. Alternatively, age-related effects or adaptive coping mechanisms may have prevented a similar second blood pressure rise despite exposure to a job strain of similar severity. However, there was also a high 19-year total mortality in the study population, which could be related to long-term health consequences of the first or both economic crises. This study provides some support for the notion that increased job strain elevates blood pressure and deteriorates outcome.

Adult↗
PubMed2006

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy.

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.

Adrenergic beta-Antagonists↗
PubMed2006

Scintigraphic demonstration of myocardial perfusion and ischaemia associated with coronary artery bypass grafting.

OBJECTIVES: To assess if myocardial perfusion scintigraphy (MPS) at rest can be of value in elucidating myocardial perfusion, ischaemia and perioperative myocardial infarction (PMI) associated with coronary artery bypass graft (CABG) surgery. DESIGN: This was a prospective randomized study of patients undergoing elective CABG. Forty-eight patients in the control group underwent serial ECG recordings and measurements of CK-MB and cTnT. Fifty-four patients in the study group were additionally examined with MPS preoperatively and 2-4 days and 6 weeks postoperatively. RESULTS: The study showed a highly significant (p < 0.001) improvement in myocardial radionuclide uptake from preoperatively to 2-4 days postoperatively. Judged from ECG and enzymatic changes, two control patients and one study patient only had PMI and no additional cases of PMI were demonstrated by MPS. CONCLUSION: MPS at rest showed that CABG significantly improved myocardial perfusion, by demonstrating an increase in radionuclide uptake. In diagnosing PMI, we found that MPS provided no additional information beyond cardiac biochemical markers and ECG changes.

Adult↗