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Biomedical subjects

J Wikstrand

Publications and source records attributed to J Wikstrand.

At least 19 recordsLinked to original sources
PubMed2006

Are serum adiponectin concentrations in a population sample of 64-year-old Caucasian women with varying glucose tolerance associated with ultrasound-assessed atherosclerosis?

OBJECTIVE: To examine whether serum adiponectin concentrations were associated with subclinical atherosclerosis assessed as intima media thickness (IMT) in the carotid arteries in Caucasian women with varying degrees of glucose tolerance. RESEARCH DESIGN AND METHODS: From a population-based cohort of 64-year-old Swedish women, 533 subjects with type 2 diabetes (DM2, n=177), impaired glucose tolerance (IGT; n=178) or normal glucose tolerance (NGT, n=178) were recruited. Anthropometrics, usual cardiovascular risk factors were examined and ultrasound examination of the carotid arteries was performed. RESULTS: Women with low adiponectin concentrations were characterized by thick IMT, higher prevalence of DM2, history of previous myocardial infarction, angina pectoris, anti-hypertensive treatment and high body mass index (BMI), waist circumference, plasma insulin, serum triglycerides, fasting glucose, HbA1c, and low serum HDL cholesterol levels. Carotid IMT correlated with HbA1c (r=0.24, P<0.001), waist circumference (r=0.22, P<0.001), plasma insulin (r=0.19, P<0.001), BMI (r=0.18, P<0.001), DM2 (r=0.16, P<0.001), systolic blood pressure (r=0.16, P<0.001), blood glucose (r=0.16, P<0.001), triglycerides (r=0.15, P<0.001), and reversely to adiponectin (r=-0.11, P=0.01), HDL cholesterol (r=-0.13, P=0.004), and alcohol intake (r=-0.087, P<0.05). A more detailed analysis of underlying associations was difficult due to a high co-linearity between these variable. CONCLUSIONS: Low serum adiponectin concentrations were associated with increased carotid artery IMT, and several risk factors for cardiovascular diseases, mainly those constituting the metabolic syndrome.

Adiponectin↗
PubMed2005

apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men.

OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.

Apolipoprotein A-I↗
PubMed2004

Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men.

OBJECTIVE: To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. DESIGN: Prospective, observational study with more than 3 years of follow-up. SETTING: One-centre study at university hospital. MATERIAL AND METHODS: The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. RESULTS: OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). CONCLUSIONS: These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.

Arteriosclerosis↗
PubMed2003

Increased Interleukin-6 levels in pituitary-deficient patients are independently related to their carotid intima-media thickness.

OBJECTIVE: Increased cardiovascular morbidity and mortality has been observed in patients with pituitary deficiency and untreated growth hormone deficiency (GHD). We investigated peripheral inflammatory and fibrinolytic markers and their associations with arterial intima-media thickness (IMT) in GHD. DESIGN: Cross-sectional study. PATIENTS: Thirty-four patients with GHD, but without cardiovascular disease, were compared to healthy controls matched for age, sex, body mass index (BMI) and smoking habits. MEASUREMENTS: IMT of the common carotid artery, C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator antigen (tPA-ag) were measured. RESULTS: Median IL-6 concentrations were increased by 208% and 248% in GHD patients compared to BMI-matched and nonobese controls, respectively. Median CRP and tPA-ag levels were increased by 237% and 167% in patients compared to nonobese controls, but not significantly different compared to BMI-matched controls. Plasma levels of fibrinogen and PAI-1 activity did not differ between groups. Age, low-density lipoprotein (LDL) cholesterol, tPA-ag and IL-6 were positively correlated, and IGF-I was negatively correlated to IMT in the patient group, but only age and IL-6 were independently related to IMT. CONCLUSIONS: IL-6 concentrations were increased in GHD patients compared to controls and independently related to IMT in patients. This finding may help to explain the variance in IMT and the increased vascular morbidity and mortality in hypopituitary patients with GHD.

Autoantigens↗
PubMed2003

Multiple risk factor intervention reduces cardiovascular risk in hypertensive patients with echolucent plaques in the carotid artery.

OBJECTIVE: In a previously published randomized 6-year study we observed that multiple risk factor intervention reduced cardiovascular risk in high-risk hypertensive men, and that this effect was confined to patients with carotid artery plaques. Hypothetically, the underlying mechanism might have been a stabilization of echolucent, instable, rupture-prone plaques. The aim of the present study was to examine plaque characteristics by B-mode ultrasound in the previous intervention study, and also to investigate the relationship between plaque characteristics at baseline and cardiovascular events during the 6-year follow-up in the two randomization groups. METHODS: High resolution B-mode ultrasound was used to characterize plaque echogenicity in four subgroups - dominantly echolucent, substantially echolucent, dominantly echogenic, and uniformly echogenic. RESULTS: In the usual care group 17 of 32 (53%) patients with echolucent plaques at baseline suffered from a combined end-point (any death or nonfatal myocardial infarction or nonfatal stroke) during follow-up compared with seven of 28 (25%) patients in the intervention group (P = 0.036). The corresponding numbers in patients with echogenic plaques were n = 4/13 (31%) and n = 4/17 (24%), respectively (NS). In the usual care group 11 of 33 (33%) patients with no plaques suffered from a combined end-point during follow-up compared with 11 of 30 (37%) in the intervention group. CONCLUSION: Our data indicate that the beneficial effect of the multiple risk intervention programme was confined to those patients with echolucent plaques. The data have to be confirmed with a large-scale trial.

Aged↗
PubMed2002

Endothelium-dependent flow-mediated vasodilatation, insulin resistance and the metabolic syndrome in 60-year-old men.

OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.

Age Factors↗
PubMed2002

Insulin, insulin propeptides and intima-media thickness in the carotid artery in 58-year-old clinically healthy men. The Atherosclerosis and Insulin Resistance study (AIR).

AIMS: To examine the relationship between specific (intact) insulin, insulin propeptides and subclinical atherosclerosis. METHODS: A cross-sectional study based on a stratified sampling of randomly selected, clinically healthy 58-year-old men (n = 391). Ultrasound examinations of the carotid arteries were performed with measurement of intima-media thickness (IMT) in the common carotid artery and in the carotid artery bulb. Fasting, cross-reacting plasma insulin (RIA), specific (intact) insulin, proinsulin, 32,33 split proinsulin and C-peptide were measured. RESULTS: Plasma concentrations of cross-reacting plasma insulin, specific insulin, proinsulin, 32,33 split proinsulin and C-peptide were univariately associated with common carotid artery IMT. Established risk factors such as blood pressure, smoking, apoB, triglycerides, body mass index (BMI), and waist--hip ratio were also related to IMT. After adjustment for smoking, apoB, blood pressure and triglycerides, cross-reacting plasma insulin, proinsulin and C-peptide but not specific insulin and split 32,33 proinsulin remained associated with carotid artery IMT. No associations remained after adjustment for BMI. CONCLUSIONS: Fasting plasma proinsulin, C-peptide, and insulin by cross-reacting RIA was associated with common carotid artery IMT independent of several conventional risk factors for atherosclerosis. The multicollinearity between the insulin peptides and propeptides makes it difficult to clarify the exact role of each peptide.

Carotid Arteries↗
PubMed2001

Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: Main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS).

BACKGROUND: Statins reduce cardiovascular events and progression of carotid intima-media thickness (IMT). beta-Blockers are also known to reduce cardiovascular events, but less is known about their effects on carotid IMT. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled, single-center trial to compare the effects of low-dose metoprolol CR/XL (25 mg once daily) and fluvastatin (40 mg once daily) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease. Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables. Death and cardiovascular events were monitored. Progression of IMT(max) in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL (-0.058 mm/y; 95% CI, -0.094 to -0.023; P=0.004; and -0.023 mm/y; 95% CI, -0.044 to -0.003; P=0.014, respectively). Incidence of cardiovascular events tended to be lower in metoprolol CR/XL-treated patients (5 versus 13 patients, P=0.055). Rate of IMT(mean) progression in the common carotid at 36 months was reduced by fluvastatin (-0.009 mm/y; 95% CI, -0.015 to -0.003; P=0.002). Women in the fluvastatin group had increased frequency of transiently high liver enzymes. CONCLUSIONS: This is the first randomized trial to show that a beta-blocker can reduce the rate of progression of carotid IMT in clinically healthy, symptom-free subjects with carotid plaque. This suggests that beta-blockers may have a favorable effect on atherosclerosis development.

Aged↗
PubMed2001

Metoprolol controlled release/extended release in patients with severe heart failure: analysis of the experience in the MERIT-HF study.

OBJECTIVES: This study analyzed the effect of the beta(1)-selective beta-blocker metoprolol succinate controlled release/extended release (CR/XL) once daily on mortality, hospitalizations and tolerability in patients with severe heart failure. BACKGROUND: There continues to be resistance to the incorporation of beta-blockers into clinical care, largely due to concerns about their benefit in patients with more severe heart failure. METHOD: SA subgroup of patients from Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT-HF) in New York Heart Association (NYHA) functional class III/IV with left ventricular ejection fraction < 0.25 were identified (n = 795). The analysis was by intention-to-treat. RESULTS: The mean ejection fraction at baseline was 0.19, and the yearly placebo mortality during follow-up was 19.1%. Treatment with metoprolol CR/XL compared to placebo resulted in significant reductions in all predefined mortality end points including: total mortality, 45 versus 72 deaths (risk reduction 39%; 95% confidence interval 11% to 58%; p = 0.0086); sudden death, 22 vs. 39 deaths (45% [7% to 67%]; p = 0.024); and death due to worsening heart failure, 13 vs. 28 deaths (55% [13% to 77%]; p = 0.015). Metoprolol CR/XL also reduced the number of hospitalizations for worsening heart failure by 45% compared with placebo (p < 0.0001). The NYHA functional class improved in the metoprolol CR/XL group compared with placebo (p = 0.0031). Metoprolol CR/XL was well tolerated, with 31% fewer patients withdrawn from study medicine (all causes) compared with placebo (p = 0.027). CONCLUSIONS: This subgroup analysis of the MERIT-HF study shows that patients with severe heart failure receive a similar mortality benefit and a similar reduction in hospitalizations for worsening heart failure with metoprolol CR/XL treatment as those patients included in the total study.

Adrenergic beta-Antagonists↗
PubMed2001

Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure - a substudy to the MERIT-HF trial.

BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity among healthy subjects, while more variable results have been observed in chronic heart failure (CHF), probably related to patients studied, methods and agent used. The effect of metoprolol controlled release/extended release (CR/XL) on peak oxygen uptake (peak VO(2)) in this patient population has not previously been investigated. AIMS: We examined the effect of long-term treatment with the selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24 females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in New York Heart Association (NYHA) functional class II-IV, and with ejection fraction <or=40%, stabilized on optimum standard therapy were randomized to metoprolol CR/XL or placebo in a double-blind trial. Exercise capacity was evaluated by peak VO(2) at baseline, after 3 months and at the end of study (mean follow-up 11.4+/-0.4 months). RESULTS: Compared with placebo metoprolol CR/XL produced a significant decrease in heart rate by 11 beats/min at rest and 18 beats/min at peak exercise. There was a tendency for a temporal decline in peak VO(2) after 3 months of therapy in both groups, but altogether peak VO(2) remained unchanged from baseline with no difference between the groups at 1 year. CONCLUSIONS: In patients with moderate to severe CHF, 11.4 months of beta(1)-blockade with metoprolol CR/XL had no effect on exercise capacity when compared with placebo or baseline.

Aged↗
PubMed2001

Relationship between C-reactive protein and intima-media thickness in the carotid and femoral arteries and to antibodies against oxidized low-density lipoprotein in healthy men: the Atherosclerosis and Insulin Resistance (AIR) study.

Results from several recent reports have linked high serum C-reactive protein (CRP) levels to atherosclerotic disease and its complications. The aims of the present study were to investigate the relationship between CRP levels and subclinical atherosclerosis, as measured by ultrasound in the carotid and femoral arteries; and also to examine whether CRP levels are associated with antibodies to oxidized low-density lipoprotein (Ox-LDL). The study group (n = 391) consisted of clinically healthy 58-year-old men recruited from the general population. CRP and antibody titres to Ox-LDL were measured by ELISA. The results showed an association between CRP and ultrasound-assessed subclinical atherosclerosis in the femoral artery (r = 0.14, P = 0.010), and also between CRP and systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, high-density lipoprotein, body mass index, waist-to-hip ratio (WHR), blood glucose, cigarette-years and antibody titres to ox-LDL (r = 0.19, P < 0.001). In this clinically healthy population of 58-year-old men, CRP levels were associated with both intima-media thickness and plaque occurrence in the femoral artery. The association between CRP and femoral atherosclerosis was not independent of smoking, serum LDL cholesterol, or systolic blood pressure. CRP levels were independently related to abdominal obesity measured as WHR, smoking and antibody titres to Ox-LDL.

Arteriosclerosis↗
PubMed2001

Sodium/lithium countertransport, insulin resistance, insulin peptides and microalbuminuria in clinically healthy 58-year-old men.

The activity of the erythrocyte transport system, sodium/lithium countertransport (SLC), has been linked to the metabolic syndrome characterized by insulin resistance and compensatory hyperinsulinaemia. We measured SLC and insulin sensitivity with the euglycaemic hyperinsulinaemic clamp method in a patient sample (n = 93) randomly selected from a large clinically healthy group of 58-year-old men (n = 818). The lipid profile, blood pressure, body mass index (BMI) and insulin were also analysed. There was a significant difference (P < 0.001) in SLC between subjects with the metabolic syndrome (n = 19) and subjects without any components of this syndrome (n = 20). There was a highly significant correlation between SLC and BMI, waist/hip ratio, total body fat mass, serum triglycerides, plasma insulin, proinsulin split products and C-peptide in a univariate analysis. There was also a significant correlation between SLC and insulin sensitivity measured as insulin-mediated glucose uptake (P < 0.01). In multiple regression analysis, only two of the variables showing univariate significance were independently correlated to SLC, i.e. serum triglycerides (P < 0.001) and BMI (P < 0.01). The subjects with a SLC value in the highest tertile had a 6-fold higher prevalence of insulin resistance (low-insulin-mediated glucose uptake) as compared with those with a SLC value in the lowest tertile. We conclude that, in clinically healthy 58-year-old men from the general population, erythrocyte SLC is closely linked to metabolic syndrome, in particular to obesity, triglycerides and insulin resistance.

Albuminuria↗
PubMed2001

A new method to quantify postexercise ST-deviation--the ST-deficit. A study in men at high and low-risk for coronary heart disease.

BACKGROUND: Quantitative heart rate adjusted exercise ST criteria like microV/beats per minute (bpm) improve the diagnostic accuracy of the exercise ECG. However, there are few quantitative HR adjusted postexercise variables available. The aim of the present exercise study was to evaluate a new such variable from computerized averaging of the postexercise ECG. METHODS: The presence of possible myocardial ischaemia in a population based sample of 74 elderly male hypertensives at high-risk of coronary heart disease, and in 42 age-matched clinically healthy males (reference group) at low-risk was assessed by exercise ECG. All men had a normal resting ECG without signs of ischaemia. VARIABLES STUDIED: standard ST-criteria, ST/HR slope < or =-2.4 microV. bpm-1, shape of the rate-recovery loop, the latter also with a new quantitative variable, the ST-deficit. RESULTS: In spite of a normal resting ECG many subjects showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and 26% in the reference group. An abnormal rate-recovery loop (ST-deficit) also contributed substantially to identify patients with possible myocardial ischaemia, 30 vs. 10%, respectively (P<0.02); cumulatively for the two HR adjusted criteria 53% vs. 29%, respectively (P<0.02). Mean ST-deficit was significantly lower in the high-risk group. CONCLUSIONS: Effort-related myocardial ischaemia is frequently silent in elderly high-risk hypertensives and necessitates testing, preferably with computerized exercise ECG and heart rate adjusted ST criteria. A new quantitative variable to assess the postexercise rate-recovery loop in the time domain, the ST-deficit is described. This variable seems to effectively discriminate between subjects with low and high-risk for coronary heart disease and thus provides new information. Further studies are warranted to validate this variable against myocardial perfusion scintigraphy and coronary angiography.

Aged↗
PubMed2001

Insulin resistance and intima-media thickness in the carotid and femoral arteries of clinically healthy 58-year-old men. The Atherosclerosis and Insulin Resistance Study (AIR).

OBJECTIVE: To examine whether insulin resistance was associated with ultrasound-assessed measures of atherosclerosis in men with varying degrees of obesity. DESIGN: A random selection of subjects from the general population were divided into quintiles of a body mass index/blood glucose score that was shown to be a valid and reproducible index of the degree of insulin sensitivity as assessed by the clamp technique. Every fourth man in quintiles 1 and 5 and every 20th man in quintiles 2-4 (in total, 104 men) were selected for an ultrasound examination of the carotid and femoral arteries and a euglycaemic hyperinsulinaemic clamp examination, adjusted for fat-free mass. SETTING: A university hospital. SUBJECTS: A total of 104 clinically healthy 58-year-old men of Swedish ancestry. RESULTS: The mean common carotid artery intima-media thickness (IMT), but not the common femoral IMT, correlated significantly with glucose infusion rate (GIR) (r = - 0.20, P < 0.05), systolic blood pressure (r = 0.20, P < 0.05), pulse pressure (r = 0.23 P < 0.01), heart rate (r = 0.20, P < 0.05), HDL cholesterol (r = - 0.18, P < 0.05), log triglycerides (r = 0.28, P < 0.01), apoA1 (r = - 0.20, P < 0.05), apoB (r = 0.21, P < 0.05), LDL particle size (r = - 0.22, P < 0.05) and plasma insulin (r = 0.20, P < 0.05). In a multiple regression, common carotid IMT was independently associated with log triglycerides (beta = 0.25, P = 0.012) and pulse pressure (beta = 0.21, P = 0.031) (R2 = 8.7%, P = 0.005) CONCLUSIONS: Insulin sensitivity, measured with the gold standard euglycaemic hyperinsulinaemic clamp method, showed similar associations with ultrasound-assessed measures of atherosclerosis in the carotid arteries as established cardiovascular risk factors, but only triglycerides and pulse pressure contributed independently to the variability in the common carotid intima-media thickness.

Arteriosclerosis↗
PubMed2001

Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up.

OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.

Aged↗
PubMed2001

Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men.

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound-assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population-based sample of clinically healthy men (n = 391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C-reactive protein (CRP) was assessed by high sensitive enzyme-linked immunosorbent assay (ELISA). Intima-media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist-hip ratio (WHR), but not with CRP or ultrasound-assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never-smokers the current smokers had higher values of WHR, triglycerides, C-reactive protein and IMT in carotid bulb and femoral artery. Ex-smokers were in general more obese and had a femoral IMT that was in-between that of never-smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex-smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.

Analysis of Variance↗
PubMed2001

Low-density lipoprotein particle size, insulin resistance, and proinsulin in a population sample of 58-year-old men.

The relationship between insulin sensitivity and low-density lipoprotein (LDL) peak particle size was examined in 104 clinically healthy 58-year-old men recruited from the general population. Insulin sensitivity was measured by the euglycemic hyperinsulinemic clamp method with adjustment for lean body mass. LDL peak particle size was determined by gradient gel electrophoresis, and insulin, proinsulin, and 32,33 split proinsulin were determined by 2-site immunoradiometric assays. The results showed that 16 subjects (15%) had pattern B, with a predominance of small LDL particles. These cases and a small LDL peak particle size were characterized by the features of the insulin resistance syndrome, ie, general and central obesity, elevated diastolic blood pressure, low serum concentrations of high-density lipoprotein (HDL) and apolipoprotein A1 (apoA1), increases in serum triglycerides and circulating insulin peptides, and low insulin-mediated glucose uptake. The correlation between insulin sensitivity and LDL peak particle size was significant (r = .33, P = .001) and independent of obesity. In a traditional multiple regression analysis, LDL peak particle size was independently associated not with insulin-mediated glucose uptake but with circulating triglycerides and HDL cholesterol, which together explained 67% of the variability in LDL particle size (P = .000). Of all insulin peptides, only proinsulin showed an independent relation to LDL peak particle size, but it disappeared after adjustment for other variables. We conclude that a small LDL particle size was associated with insulin resistance among these clinically healthy men, but this was not independent of serum triglycerides and HDL cholesterol. Serum proinsulin was more directly related to LDL particle size than insulin.

Glucose↗