Bo Hedblad

Relation between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects. Results from a cross‐sectional study in Malmö, Sweden

Aimsu2003To assess whether there is an association between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects free from symptomatic cardiovascular disease.

Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmö Preventive Project)

Aims Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. Methods and results Prospective data of the Swedish ‘Malmö Preventive Project’ (n = 33 346, 67.3% men, mean age 45.7 ± 7.4 years, mean follow-up 22.7 ± 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall ≥30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3–1.9, P < 0.0001 and 1.6, 95% CI 1.2–2.1, P = 0.001] and diastolic BP fall ≥15 mmHg (HR: 1.4, 95% CI 1.1–1.9, P = 0.024 and 1.7, 95% CI 1.1–2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction. Conclusion Orthostatic hypotension can be detected in ∼6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease.

Incident coronary events and case fatality in relation to common carotid intima‐media thickness

Objectives.u2002 To evaluate the incidence of coronary events (CE) and case fatality in relation to common carotid intima‐media thickness (IMT) and carotid plaque over a median follow up of 7u2003years.

Effects of Cholesterol and Inflammation-Sensitive Plasma Proteins on Incidence of Myocardial Infarction and Stroke in Men

Background—Although cholesterol is a major cardiovascular risk factor, its association with stroke remains controversial. This study explored whether the cholesterol-related incidence of stroke and myocardial infarction is modified by plasma markers of inflammation in a large, population-based cohort with a long follow-up. Methods and Results—Plasma cholesterol and 5 inflammation-sensitive plasma proteins (ISP) (fibrinogen, &agr;1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid) were determined in 6063 healthy men, 28 to 61 years of age. The incidence of stroke, cardiac events (fatal and nonfatal), and cardiovascular deaths was compared between groups defined by levels of cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined as 2 to 5 ISP in the top quartile. High cholesterol was associated with higher levels of ISP. Hypercholesterolemia (≥6.5 mmol/L, 251 mg/dL) was associated with an increased incidence of ischemic stroke and cardiac events and with a reduced incidence of intracerebral hemorrhage. The ISP levels modified these associations. After risk factor adjustment, men with hypercholesterolemia and high ISP levels had a significantly higher risk of cardiovascular death (relative risk [RR]=2.4; CI, 1.8 to 3.3), cardiac events (RR=2.3; CI, 1.8 to 3.0), and ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal cholesterol and low ISP levels. In the absence of high ISP levels, hypercholesterolemia was associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0 to 2.0) and cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with ischemic stroke (RR=1.25; CI, 0.8 to 2.0). Conclusions—Hypercholesterolemia is associated with high plasma levels of ISP. These proteins increase the cholesterol-related incidence of cardiovascular diseases. In the absence of elevated ISP levels, no statistically confirmed association was found between hypercholesterolemia and ischemic stroke.

Insulin resistance in non‐diabetic subjects is associated with increased incidence of myocardial infarction and death

Aims To compare the incidence of myocardial infarction and death in non‐diabetic subjects with and without insulin resistance.

Sleep disturbance in association with elevated pulse rate for prediction of mortality - consequences of mental strain?

Abstract.u2002Nilsson PM, Nilsson J‐Å, Hedblad B, Berglund G (University Hospital, Malmö, Sweden). Sleep disturbance in association with elevated pulse rate for prediction of mortality – consequences of mental strain? J Intern Med 2001; 250: 521–529.

Blood Pressure Increase and Incidence of Hypertension in Relation to Inflammation-Sensitive Plasma Proteins

Objective—The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. Method and Results—Blood pressure and plasma levels of fibrinogen, &agr;1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (±2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (±SD) increase in systolic blood pressure was 18.8±17, 19.2±17, 19.3±17, and 22.1±18 mm Hg, respectively, for men with 0, 1, 2, and ≥3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5±14, 15.8±14, 17.4±14, and 17.8±15 mm Hg, respectively (P =0.02). Incidence of hypertension (≥160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. Conclusions—Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease.

Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers

In prospective cohort studies, person-time time is calculated from baseline until the first definite event occurs or until censoring. A way to correctly identify and date definite events when only routine registers are available is to retrieve all hospital discharge notes and death certificates with a diagnosis of probable event and perform a consecutive revision. It is important to detect all possible hospital stays as they may contain useful information for the revision study. Furthermore, loss to follow-up can be avoided by extending the retrieval outside the specific geographical area where the cohort was defined. The aims of this study were (i) to describe a comprehensive retrieval of probable myocardial infarctions (diagnosis with International Classification of Diseases 8th and 9th revisions codes 410–414) or stroke (codes 430–438), (ii) to quantify the relative efficiency of different local and national routine registers or their combination compared with the use of all available registers together, and (iii) to audit local and national registers by comparing their outcome at the county level. The study was performed in two prospective cohorts studies i.e., `Men-born-1914 (n = 500) from Skåne (period 1982–1993), and Skara-1 (n = 683) from Skaraborg (period 1988–1994.). All available routine registers were linked to the cohorts. The use of all available routine registers improved retrieval of both individual and hospital stays with a discharge diagnosis of probable event and gave an enhanced basis for a future validation study. Local registers were not completely covered by the national register, but the accessible combination of national in-patient and mortality registers was an efficient alternative.

Cardiac Arrhythmias and Stroke: Increased Risk in Men With High Frequency of Atrial Ectopic Beats

Background and Purpose With the exception of atrial fibrillation (AF), little scientific attention has been given the associations between cardiac arrhythmias and incidence of stroke. We sought to study whether atrial and ventricular arrhythmias assessed during a 24-hour ambulatory ECG registration are associated with incidence of stroke. Methods The population-based cohort “Men Born in 1914” was examined with 24-hour ambulatory ECG registrations at 68 years of age. Four hundred two men without previous myocardial infarction or stroke were included, and 236 of them had hypertension (≥160/95 mm Hg or treatment). Fourteen-year rates of stroke (fatal and nonfatal) and all-cause mortality were updated from national and regional registers. Frequent or complex ventricular arrhythmias was defined as Lown class 2 to 5. A high frequency of atrial ectopic beats (AEB) was defined as the fifth quintile (ie, ≥218 AEB per 24 hours). Results Fifty-eight men suffered a first stroke during the follow-up. Stroke rates (per 1000 person-years) among men with AF (n=14), with frequent AEB (n=77), and without AF or frequent AEB (n=311) were 34.5, 19.5, and 11.6, respectively. The corresponding values among men with hypertension were 40.7, 32.3, and 14.7, respectively. Frequent AEB (compared with absence of AF and frequent AEB) was significantly associated with stroke among all men (relative risk=1.9; 95% CI, 1.02 to 3.4; P=0.04) and among hypertensive men (relative risk=2.5; 95% CI, 1.3 to 4.8; P=0.009) after adjustments for potential confounders. The increased stroke rates among men with Lown class 2 to 5 did not reach statistical significance. Conclusions A high frequency of AEB is associated with an increased incidence of stroke.

Long-Term Effects of Inflammation-Sensitive Plasma Proteins and Systolic Blood Pressure on Incidence of Stroke

Background and Purpose— The present study investigated the relationships between inflammation-sensitive plasma proteins (ISPs) and systolic blood pressure (SBP), as well as the joint long-term effects of ISP and SBP on incidence of stroke. Methods— BP and 5 ISPs (fibrinogen, &agr;1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) were assessed in 6071 healthy men 28 to 61 years of age. All-cause mortality and incidence of stroke were monitored over a mean follow-up of 18.7 years in men defined by SBP (<120, 120 to 139, ≥140 mm Hg) and ISP (0 to 1 or 2 to 5 ISPs in the top quartile). Results— SBP and diastolic BP were significantly and positively associated with the number of ISPs in the top quartile. As expected, elevated SBP was associated with an increased incidence of stroke. Among men with SBP ≥140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP ≥140 mm Hg and high ISP levels had a relative risk of stroke of 4.3 (95% CI, 2.3 to 7.8) compared with men with SBP <120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP ≥140 was 2.5 (95% CI,1.4 to 4.6). Men with high ISP levels had a significantly increased risk of stroke also after exclusion of the events from the first 10 years of follow-up. Conclusions— High ISP levels are associated with elevated BP. These proteins are associated with an increased risk of stroke among men with high BP and provide information on stroke risk even after many years of follow-up.