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Biomedical subjects

Henrik Sillesen

Publications and source records attributed to Henrik Sillesen.

15 recordsLinked to original sources
PubMed2006

Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular death in patients with carotid stenosis.

BACKGROUND: Matrix metalloproteinase-9 could exhibit an important role in the destabilization of atherosclerotic carotid plaques. We hypothesized that in patients with carotid stenosis, elevated levels of plasma matrix metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular death. METHODS AND RESULTS: We followed up 207 patients with > or = 50% carotid stenosis initially for a mean of 4.4 years, during which time 53 patients developed ipsilateral stroke or died of cardiovascular causes. The cumulative incidence of ipsilateral stroke or cardiovascular death was higher in those with matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank P=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and below the median, respectively. Elevated matrix metalloproteinase-9 and an echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9 and an echorich plaque had a hazard ratio for ipsilateral stroke or cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of 3.3 (95% CI, 1.1 to 9.7). CONCLUSIONS: Elevated levels of matrix metalloproteinase-9 in patients with > or = 50% carotid stenosis were associated with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining elevated matrix metalloproteinase-9 and plaque echolucency was associated with a 4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for ipsilateral stroke.

Aged↗
PubMed2006

High-dose atorvastatin after stroke or transient ischemic attack.

BACKGROUND: Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established. METHODS: We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke. RESULTS: The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin. CONCLUSIONS: In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number, NCT00147602 [ClinicalTrials.gov].).

Adult↗
PubMed2005

Ankle brachial index, C-reactive protein, and central augmentation index to identify individuals with severe atherosclerosis.

OBJECTIVES: We examined the ability of ankle brachial index, C-reactive protein and central augmentation index to identify individuals in the general population with severe atherosclerosis, diagnosed as those with ischaemic cardiovascular disease. METHODS AND RESULTS: We examined 4159 randomly sampled individuals from the Danish general population, of which 250 had severe atherosclerosis. After adjustment for gender and age, individuals with ankle brachial index of 0.71-0.90 and <0.70 vs. 0.91-1.10 had odds ratios for severe atherosclerosis of 1.6 (95%CI:1.1-2.3) and 2.9 (1.9-4.6), respectively. C-reactive protein of >3.0 or 1.0-3.0 mg/L vs. <1.0 mg/L as well as central augmentation index in quintiles did not identify individuals with severe atherosclerosis, and did not improve further the ability of ankle brachial index to identify such individuals. On a continuous scale using receiver operating characteristics curves, presence of severe atherosclerosis was predicted by ankle brachial index (P=0.00000003), C-reactive protein (P=0.000003), as well as central augmentation index (P=0.001); these three curves did not differ. CONCLUSION: Ankle brachial index <0.9 identify individuals with severe atherosclerosis in the general population, while C-reactive protein in three groups and central augmentation index in quintiles did not. On a continuous scale, all three variables predicted severe atherosclerosis.

Adult↗
PubMed2005

Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population.

CONTEXT: Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial. OBJECTIVE: We tested the hypothesis that the APOB 7673C>T polymorphism (T2488T) is associated with variation in low-density lipoprotein (LDL) levels and with risk of ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and total mortality in the general population. DESIGN: The design was a cohort study with 22-yr follow-up (166,232 person years) and two case-control studies, The Copenhagen City Heart Study. SETTINGS: The study was performed within the Danish general population and at a university hospital. PARTICIPANTS: The study was comprised of 9185 individuals from the general population, 2157 patients with IHD, and 378 patients with ICVD. MAIN OUTCOME MEASURES: The main outcome measures were lipids, lipoproteins, apolipoproteins (apo), IHD, ICVD, and total mortality. RESULTS: Genotype was associated with increases in total cholesterol (women/men), LDL cholesterol, and apoB of 0.20/0.26 mmol/liter (3.3%/4.4%), 0.22/0.28 mmol/liter (5.9%/7.8%), and 5.0/5.6 mg/dl (5.9%/6.7%) in TT vs. CC homozygotes, respectively. These results were consistent over time. Despite this, the 7673C>T polymorphism was not associated with risk of IHD, ICVD, or total mortality prospectively or in case-control studies. CONCLUSION: The APOB 7673C>T polymorphism is associated with moderate increases in total cholesterol, LDL cholesterol, and apoB in both genders in the general population, but not with risk of IHD, ICVD, or total mortality.

Adult↗
PubMed2003

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↗
PubMed2003

Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study.

BACKGROUND: Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity. METHODS AND RESULTS: We genotyped 7963 control subjects from the adult general population of Denmark, 1131 Danish patients with ICVD, and 2221 Danish patients with IHD. Compared with MM/MS individuals, systolic blood pressure was lower by 15 mm Hg in ZZ homozygotes (n=6, P=0.03) and 9 mm Hg in MZ heterozygotes with IHD (n=39, P=0.02). Odds ratios for ICVD and IHD in MZ versus MM/MS individuals were 0.70 (0.51 to 0.96) and 0.77 (0.61 to 0.98). Finally, mean ages of MZ and MM/MS control subjects were 58 and 56 years (Mann-Whitney: P=0.008), and relative alpha(1)-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (chi(2), P=0.002). CONCLUSIONS: ZZ alpha(1)-antitrypsin deficiency and MZ intermediate deficiency in the context of IHD are associated with reduced blood pressure, and MZ is associated with reduced risk of ICVD and IHD. Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition.

Adult↗
PubMed2003

Echolucent rupture-prone plaques.

PURPOSE OF REVIEW: Routine measurement of echolucency of atherosclerotic plaques, in addition to degree of stenosis, may change clinical practice in the future. Within the context of previous knowledge in this field, we therefore review recent developments in detection and histological characterization of echolucent rupture-prone plaques and risk for ischaemic events associated with them, as well as risk factors and treatment for such plaques. RECENT FINDINGS: Plaque echolucency is associated with increased lipid content and macrophage density (and sometimes haemorrhage), whereas fibrous tissue (and sometimes calcification) dominates echo-rich plaques. Echolucent carotid plaques are associated with higher risk for future ischaemic stroke, particularly in previously symptomatic individuals, and possibly with risk for restenosis after endarterectomy as well as myocardial infarction. These plaques also associate with elevated levels of triglyceride-rich lipoproteins (and with reduced levels of HDL), but not with elevated levels of LDL or acute phase reactants. Risk factor intervention may be more beneficial for patients with echolucent plaques than in those with echo-rich plaques, whereas coronary stenting may be less efficient in patients with echolucent plaques. SUMMARY: If it is to be clinically useful, then the ultrasound method must be further improved such that it may accurately detect echolucent rupture-prone plaques in the individual patient. Furthermore, the possible superior benefit from preventive treatments deployed selectively in patients with echolucent plaques must be better documented in large randomized trials. When these two requirements are met, routine measurement of plaque echolucency could change clinical practice with respect to the preventive treatments that are offered to patients with echolucent plaques as compared with those without such plaques.

Animals↗
PubMed2002

Serum lipids act as inverse acute phase reactants and are falsely low in patients with critical limb ischemia.

BACKGROUND: Lipid levels generally fall after an acute myocardial infarction. This study was conducted to see what trends lipid levels had in patients who underwent operation for critical limb ischemia. METHODS: The study was prospective and included 30 patients who underwent operation for critical limb ischemia. Serum lipid profiles and C-reactive protein were analyzed before surgery and 3 months after peripheral bypass surgery. In addition, comparison of lipid levels after surgery was made with 287 healthy and 283 ischemic heart disease controls from The Copenhagen City Heart Study. RESULTS: Total, low density lipoprotein, and high density lipoprotein cholesterol levels were found to be significantly lower before surgery than 3 months after surgery (P <.001). In contrast, C-reactive protein was higher before surgery and decreased after 3 months (P <.0001). An inverse linear correlation was found between total cholesterol/low density lipoprotein cholesterol and C-reactive protein (P <.001 and P <.04, respectively). Comparison with controls showed that cholesterol levels 3 months after surgery were significantly lower (P <.009). CONCLUSION: Serum cholesterol levels are not reliable in the preoperative period and should therefore be measured at least 3 months after surgery when they seem to approach a more representative level.

Acute-Phase Proteins↗
PubMed2002

Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels.

OBJECTIVE: Atherosclerosis may be regarded as an inflammatory disease dominated by macrophages. We tested whether macrophages in carotid artery atherosclerotic plaques are associated with echolucency on B-mode ultrasound imaging, lipid levels, inflammatory markers, and aspirin use. METHODS: We studied 106 patients undergoing carotid endarterectomy having >/=50% carotid artery stenosis and previous ipsilateral hemispheric neurologic symptoms. RESULTS: Macrophages were particularly common in plaques with a high content of lipid and hemorrhage and, conversely, rare in plaques dominated by calcification and fibrous tissue. Macrophage density in carotid artery plaques classified by B-mode ultrasound imaging as echolucent (n = 56), intermediate (n = 25), or echorich (n = 25) was 1.8% +/- 0.2%, 1.5% +/- 0.4%, and 1.0% +/- 0.2% (+/-SE), respectively (analysis of variance, P =.02). A computer-generated measure of plaque echolucency, gray-scale median, was associated with increased macrophage density (r = -0.31; P =.002). Furthermore, plasma and low-density lipoprotein cholesterol levels were associated with carotid artery macrophage density (r = 0.26, P =.008 and r = 0.23, P =.02); this was most pronounced in patients with lipid-rich plaques. Macrophage density was not associated with plasma levels of acute-phase reactants. Finally, macrophage density in carotid artery plaques of users (n = 55) and nonusers of aspirin (n = 51) was 1.2% +/- 0.2% and 1.8% +/- 0.2% (t test, P =.01). CONCLUSIONS: Increased macrophage density in carotid atherosclerotic plaques was associated with lipid content, plaque echolucency, and increased plasma and low-density lipoprotein cholesterol levels. Furthermore, use of aspirin was associated with reduced macrophage density in carotid artery plaques.

Analysis of Variance↗
PubMed2002

Echolucent, rupture-prone carotid plaques associated with elevated triglyceride-rich lipoproteins, particularly in women.

BACKGROUND: We tested whether fasting and postprandial triglyceride-rich lipoprotein elevations are gender specific (1) in patients with carotid artery stenosis >or=50% vs controls, and (2) in patients with echolucent, rupture-prone plaques compared with controls. METHODS AND RESULTS: We studied 66 controls and 323 patients with carotid artery stenosis >or=50%, of which 160 had echolucent plaques. Participants underwent a fat-tolerance test and carotid artery plaque evaluation with use of high-resolution B-mode ultrasound and computerized image analysis. By comparison, female cases with carotid stenosis >or=50% had higher fasting and postprandial triglyceride levels than did controls; however, this difference was not observed between male cases and controls. Fasting and postprandial very-low-density lipoprotein (VLDL) and intermediate density liprotein (IDL) cholesterol levels were elevated; low density lipoprotein (LDL) cholesterol level was unchanged, and high density lipoprotein (HDL) cholesterol level was reduced in both female and male cases vs controls. Fasting and postprandial triglyceride levels were elevated in women with echolucent plaques vs controls, but not in women with echo-rich plaques, or in men with echolucent or echo-rich plaques. Fasting and postprandial VLDL and IDL cholesterol levels were elevated, LDL cholesterol level was unchanged, and HDL cholesterol level was reduced in both female and male patients with echolucent plaques vs controls. CONCLUSIONS: Fasting and postprandial triglyceride-rich lipoproteins (but not LDLs) are elevated in patients with carotid artery stenosis of >or=50% compared with controls, and particularly identify echolucent, rupture-prone carotid plaques. These observations are more pronounced in women than in men.

Adult↗
PubMedDate not supplied

The natural history of patients with carotid stenosis.

Atherosclerosis is a systemic disease affecting the circulatory system throughout the body. Thus, patients with atherosclerosis of the carotid arteries are not only at risk of stroke but also of other manifestations of the disease, i.e. vascular death, myocardial infarction etc. So far, intervention trials evaluating the effect of treatment of this patient group, i.e. by surgical removal of the carotid lesion, has focussed on degree of stenosis of the lesion. However, many other factors may be of importance: local factors of the lesion (morphology, degree of stenosis), hemodynamic factors (collateral compensation) and systemic factors (clinical symptoms, accompanying diseases, risk factor control). Recent findings suggest that plaque morphology (composition and structure) may be of greater importance than the degree of stenosis and it may be speculated if current indications for carotid endarterectomy are optimal.

Carotid Stenosis↗