Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study.

Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (+/-2.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (<160/95 mm Hg), incidence of hypertension (>or=160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P=0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean+standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5+0.8, 19.6+0.9, 19.8+0.8 and 20.8+0.8 mm Hg, respectively, in the C3 quartiles (trend: P=0.004). C3 was not associated diastolic blood pressure at follow-up. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

Fatality of acute coronary events in relation to hypertension and low-grade inflammation: a population-based cohort study.

Hypertension has been associated with increased case-fatality rates among individuals who subsequently suffer from acute coronary events. It is unknown whether inflammation modifies this relationship. This population-based study explored the effects of inflammation and hypertension on incidence of coronary event, and on the fatality of the future events. Blood pressure (BP) and five inflammation-sensitive plasma proteins (ISPs, fibrinogen, orosomucoid, alpha 1-antitrypsin, haptoglobin and ceruloplasmin) were determined in 6071 healthy men. During the mean follow-up of 19 years, 679 men had a first coronary event (non-fatal myocardial infarction or death from coronary heart disease). Of them, 197 (29%) were fatal cases (death during the first day). As expected, hypertension was associated with increased incidence of coronary events and increased proportion of fatal cases. At all levels of BP, high ISPs (> or =2 ISPs in top quartile) significantly added to the incidence of events. Men with high ISPs had the highest case-fatality rates. The difference in case-fatality rate between men with and without high ISPs was, however, significant only in men with normal BP (<130/85 mm Hg) (33 vs 19%, P < 0.05), and not in men with moderate or severe hypertension (> or =160/100 mm Hg) (40 vs 35%, P = 0.32). High ISPs add to the incidence of coronary events at all levels of BP. Hypertension and inflammation are both independently associated with increased case-fatality in subjects who later have an acute coronary event. The influence of ISPs on the case-fatality rate seems to be most important in men with normal BP.

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.

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, alpha1-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 (> or =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.

Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins.

BACKGROUND: The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. METHODS AND RESULTS: Forced vital capacity (FVC) and plasma levels of fibrinogen, alpha(1)-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to approximately 25% of the excess risk. The risk factor-adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to approximately 10% to 15% of the excess risk. Among men with low FVC, the risk factor-adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (> or =2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (< or =1 protein in top quartile; reference, top quartile of FVC and low protein levels). CONCLUSIONS: FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.

Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from "men born in 1914," Malmö, Sweden.

BACKGROUND: Reduced lung function has been associated with increased rates of myocardial infarction. Whether the occurrence and prognostic significance of ventricular arrhythmia is related to lung function is largely unknown. METHODS AND RESULTS: We performed a population-based study of 68-year-old men without a history of stroke or myocardial infarction; 402 men participated. Mortality and coronary events (fatal or nonfatal) were studied in relation to ventricular arrhythmia during 24 hours, percentage of the predicted forced expiratory volume (FEV1(%pred)), vital capacity (VC(%pred)), and the FEV/VC ratio. During 14 years of follow-up, 181 men died and 87 experienced a coronary event. Occurrence of frequent or complex ventricular arrhythmia (Lown class 2 to 5) was significantly and inversely associated with FEV1(%pred). Men with Lown class 2 to 5 and a low FEV1(%pred) (below median) had significantly higher mortality (71.5 versus 26.8 per 1000 person-years; P<0.0001) and coronary event rates (37.7 versus 18.0; P=0.02) than men with Lown class 2 to 5 and a high FEV1(%pred). These associations remained significant after adjustments for potential confounders (mortality: relative risk [RR], 2.91; 95% CI,1.68 to 5.04; coronary events: RR, 2.16; 95% CI, 1.07 to 4.37). In men without frequent or complex arrhythmia (Lown 0 to 1), a low FEV1(%pred) was not significantly associated with mortality (RR, 1.37; 95% CI, 0.92 to 2.05) or coronary events (RR, 1.24; 95% CI, 0.67 to 2.27) after adjustments for confounders. The FEV/VC ratio showed similar associations with arrhythmia, mortality, and coronary events. CONCLUSIONS: Lung function is inversely associated with the occurrence of ventricular arrhythmia. The increased incidence of myocardial infarction and death associated with arrhythmia was mainly limited to men with a low FEV1(%pred) or FEV/VC. We suggest that lung function should be considered when assessing the prognostic significance of ventricular arrhythmia.

Incidence of stroke is related to carotid IMT even in the absence of plaque.

BACKGROUND: The carotid intima-media thickness (IMT) has been associated with incidence of stroke. Whether this association is independent of carotid plaque is controversial. METHODS AND RESULTS: The associations among B-mode ultrasound determined common carotid IMT, carotid plaque (focal IMT>1.2mm) and incident stroke, were investigated in 5163 Swedish middle-aged men and women over a median follow-up of 7 years. Age and sex-adjusted carotid IMT, and carotid plaque were significantly (p<0.05) related to future stroke. Adjustment for cardiovascular risk factors generally reduced the hazard rate ratios, however more prominently so with regard to the carotid measure of plaque than with IMT. The associations between carotid IMT and stroke remained after adjustment for presence of carotid plaque, and graded associations between carotid IMT and stroke was found both among those with and without carotid plaque. CONCLUSIONS: In this population-based study, common carotid IMT was associated with incidence of stroke. This relation was independent of presence of carotid plaque.

Risk of myocardial infarction and stroke in smokers is related to plasma levels of inflammation-sensitive proteins.

BACKGROUND: The extent to which differences in cardiovascular risk between smokers with similar daily tobacco consumption may be related to plasma levels of inflammation-sensitive proteins (ISP) and whether these proteins are associated with levels of carboxyhemoglobin (COHb%) have not been clarified. METHODS AND RESULTS: In a population-based cohort of 1489 never smokers, 1685 former smokers, and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. COHb% levels were available for 2098 of them. Incidence of myocardial infarction, stroke, and death were monitored over 18.7+/-4.7 years. The proportion with high ISP levels (ie, > or =2 ISP in the top quartile) increased progressively with daily tobacco consumption (P<0.01) and COHb% (P<0.01). In all smoking categories, the incidence of stroke, cardiac events, and death was related to ISP. In heavy smokers, high ISP levels were associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to 2.03) for cardiac events and death, respectively. Corresponding figures for moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49), respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively. CONCLUSIONS: ISP levels are related to COHb% in smokers. High levels are associated with an increased cardiovascular risk.

Influence of plasma fibrinogen levels on the incidence of myocardial infarction and death is modified by other inflammation-sensitive proteins: a long-term cohort study.

Inflammation may play an important role in atherosclerotic disease. Plasma fibrinogen is an established predictor of cardiovascular events. The aim of this study was to evaluate whether other inflammation-sensitive plasma proteins modify this prediction. We studied the incidence of cardiac events and death in men in relation to fibrinogen levels alone and in combination with other proteins. The study was based on 6075 men, who were, on average, 46 years old at the time of the screening examination, which included the quantitative assessment of plasma levels of fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. The concentration of each protein was divided into quartiles for each. This classification made it possible to identify 4 groups, ie, men in the first fibrinogen quartile and at the same time either not belonging to the fourth quartile of any of the other proteins (Q1/No group) or also belonging to the fourth quartile of >/=1 of the additional proteins (Q1/Yes group) and corresponding groups in the fourth fibrinogen quartile (Q4/No and Q4/Yes groups). During the follow-up, which occurred at an average of 16 years, 439 (7.2%) men experienced a cardiac event, and 653 (10.7%) died; 278 of these men died of cardiovascular diseases, with 206 deaths attributed to ischemic heart disease. From the lowest to the highest quartile, there was for each protein a stepwise increase in the incidence of cardiac events and mortality. All-cause mortality and cardiovascular mortality were significantly higher in the Q4/Yes group compared with the Q4/No group, but they were similar in the Q4/No and Q1/Yes groups. The incidence of cardiac events was significantly higher in the Q1/Yes and Q4/Yes groups compared with the Q1/No and Q4/No groups, respectively. The increased cardiovascular mortality and cardiac event rates remained after adjustment for several confounders when the Q4/Yes and Q4/No groups were compared. The results suggest that the incidence of cardiac events and death due to cardiovascular diseases in middle-aged men predicted by plasma levels of fibrinogen is modified by other inflammation-sensitive proteins.

Reduced cardiovascular mortality risk in male smokers who are physically active. Results from a 25-year follow-up of the prospective population study men born in 1914.

OBJECTIVE: To assess to what extent physical activity during leisure time may modify the mortality risk associated with smoking. METHODS: Population-based cohort study in the city of Malmö, Sweden. The 642 men included in this study were all born in 1914 and were all free of cardiovascular disease at the baseline examination in 1968 and 1969. Smoking habits and physical activity during leisure time were assessed by a structured questionnaire. Main outcome measures were total and cardiovascular mortality rates during 25 years of follow-up. RESULTS: The total and cardiovascular mortality rates in smokers were 33.2 per 1000 person-years and 15.9 per 1000 person-years, respectively. Corresponding figures in nonsmokers were 17.8 per 1000 person-years and 7.5 per 1000 person-years. Mortality rates in smokers were strongly related to daily tobacco consumption. Physically active men had lower overall (adjusted relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.9) and cardiovascular (adjusted RR, 0.6; 95% CI, 0.3-0.9) mortality rates than sedentary men. Physically active men who never smoked (used as the control category) had the lowest death rate, and physically inactive smokers the highest (adjusted RR, 3.6; 95% CI, 2.1-6.3). The cardiovascular death rates in these 2 groups were 4.3 per 1000 person-years and 16.6 per 1000 person-years, respectively (adjusted RR, 5.5; 95% CI, 2.2-13.6). Vigorous physical activity in smokers was associated with an almost 40% lower cardiovascular mortality rate (RR, 0.6; 95% CI, 0.3-1.2; P = .11). CONCLUSIONS: Regular physical activity was associated with lower total and cardiovascular mortality rates. Similar effects were observed in both nonsmokers and smokers.

Progression of retinopathy after change of treatment from oral antihyperglycemic agents to insulin in patients with NIDDM.

OBJECTIVE: In insulin-dependent diabetes mellitus, institution of good glycemic control has been shown to retard development of retinopathy even though temporary progression has occurred. Few data have been available from patients with non-insulin-dependent diabetes mellitus (NIDDM). To determine the impact of improved glycemic control on retinopathy in patients with NIDDM, we examined, in a case-control study, the progression of retinopathy in 94 patients who changed treatment from oral antihyperglycemic agents to insulin. RESEARCH DESIGN AND METHODS: We used the Wisconsin retinopathy scale and related progression of retinopathy during a 2-year observation period to changes in HbA1c after institution of insulin therapy. RESULTS: Progression of retinopathy > or = 3 levels occurred in 23% of the patients and was significantly more common in the patient group in which HbA1c was lowered > or = 3% compared with progression in the group in which HbA1c was lowered < 3% (P = 0.0001; relative risk 3.2; 95% confidence interval 1.5-6.9). CONCLUSIONS: Improved glycemic control as achieved by insulin therapy may be associated with worsening of retinopathy in patients with NIDDM.

Adaptive behavior in stressful situations and stroke incidence in hypertensive men: results from prospective cohort study "men born in 1914" in Malmö, Sweden.

BACKGROUND AND PURPOSE: Although hypertension is a major risk factor for stroke, many hypertensive persons remain healthy. The aim of the present study was to analyze whether adaptation in a stressful situation was associated with the incidence of stroke in hypertensive men. METHODS: Two hundred thirty-eight hypertensive men were followed from baseline in 1982/1983 until first stroke, death, or December 31, 1996. Adaptation to stress was studied with the serial Color-Word Test. In the Regression dimension, 4 patterns of adaptation could be distinguished according to mastering of the test. Successful mastering of the test was shown in stabilized patterns, increasing difficulty in cumulative patterns, fluctuating difficulty in dissociative patterns, and fluctuating difficulty that increased during testing in cumulative-dissociative patterns. The patterns were compared regarding stroke incidence. RESULTS: Forty-three men experienced a stroke during follow-up. Stroke rates per 1000 person-years were 12.6 for men with stabilized patterns, 14.3 for men with cumulative patterns, 16.2 for men with dissociative patterns, and 31.2 for men with cumulative-dissociative patterns. Multivariate analysis, adjusted for relevant cerebrovascular risk factors, showed that the cumulative-dissociative pattern of the Regression dimension was associated with an increased risk of stroke during follow-up (relative risk 3.00, 95% CI 1.32 to 6.81). CONCLUSIONS: The specific behavior pattern, characterized by the greatest difficulties in managing the test, was associated with incidence of stroke in hypertensive men. One interpretation is that hypertensive men who chronically fail to find successful strategies in stressful situations are vulnerable to the damaging effects of stress and thereby at an increased risk of a future stroke.

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, alpha1-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.

Geographic distribution of stroke incidence within an urban population: relations to socioeconomic circumstances and prevalence of cardiovascular risk factors.

BACKGROUND AND PURPOSE: Geographic differences in stroke incidence indicate a potential for prevention. The present study from the city of Malmö, Sweden, sought to investigate whether incidence of stroke in residential areas is related to prevalence of cardiovascular risk factors and socioeconomic circumstances. METHODS: The Stroke Register in Malmö, Sweden, was used for retrieval of the 3540 patients who suffered a first stroke between 1989 and 1998. The Malmö Diet and Cancer cohort (n=28 466) was used to assess area specific prevalence of hypertension, diabetes, smoking, and being overweight and for computation of a cardiovascular risk score. Socioeconomic circumstances for the 17 administrative areas were expressed in terms of a composite score. RESULTS: Standardized stroke incidence ranged among areas from 437 to 743 per 100 000 for men and from 223 to 518 per 100 000 for women. Socioeconomic score correlated significantly with area-specific stroke rates among men (r=-0.62, P=0.008) and women (r=-0.67, P=0.004). Incidence of stroke was significantly associated with cardiovascular risk score for each area (men, r=0.53, P<0.05; women, r=0.76, P<0.001). The cardiovascular score and the socioeconomic score together accounted for 44% of the geographic variance among men and 63% among women. CONCLUSIONS: Marked differences occurred in stroke incidence among residential areas within this urban population. High-rate areas were characterized by a higher prevalence of smoking, hypertension, diabetes, and being overweight and by inferior socioeconomic circumstances. These risk factors accounted for a substantial proportion of the geographic variance in incidence of stroke.

Hypertension and ST segment depression during ambulatory electrocardiographic recording. Results from the prospective population study 'men born in 1914' from Malmö, Sweden.

The aim of this study in 341 men (aged 68 years) without history of ischemic heart disease was to study the relation between hypertension and silent ischemic-type ST segment depression during ambulatory long-term electrocardiographic recording and to assess the influence between these two variables on cardiovascular morbidity and mortality rates. Seventy-nine men (23%) demonstrated one or more episodes of silent ischemic ST segment depression. One hundred and sixty-seven men (49%) were considered to have hypertension (i.e., they had a diastolic blood pressure of 95 mm Hg or greater or were treated with antihypertensive therapy). Forty-nine (72%) of the 68 treated hypertensive subjects were classified as uncontrolled (i.e., their diastolic blood pressure was 95 mm Hg or greater). The occurrence of ischemic ST depression was higher in hypertensive men (28%) than in normotensive men (19%). The highest incidence of ischemic ST depression (41%) was observed in treated hypertensive men with inadequate blood pressure control. Cardiac event rate during a 53-month follow-up was 6.6% in hypertensive men and 4.6% in normotensive men. Uncontrolled treated hypertensive men had a higher event rate (14%) than hypertensive men overall. Hypertensive men with inadequate blood pressure control and who demonstrated ST segment depression had the highest event rate (25%).

Influence of carboxyhemoglobin, gamma-glutamyl-transferase, body weight, and heart rate on blood pressure in middle-aged men.

Carboxyhemoglobin (COHb%) and gamma-glutamyl-transferase (GGT) are indicators of tobacco and alcohol consumption; similarly, body weight broadly reflects dietary habits. Relationships between COHb%, GGT, relative body weight, heart rate and blood pressure were studied in 242 48-year-old men attending a general health screening program in Malmö, Sweden. All were without treatment for high blood pressure. Positive correlations were found between blood pressure and body weight, GGT, and pulse, and a reciprocal correlation between blood pressure and COHb%. Use of objective markers for known or suspected risk factors, such as alcohol consumption, smoking, or overweight, were studied to elucidate their usefulness for further prospective studies.

Influence of cigarette smoking on goiter formation, thyroglobulin, and thyroid hormone levels in women.

The possible influence of cigarette smoking on goiter formation, thyroglobulin (Tg) secretion, and thyroid hormone production was assessed by estimations of the presence of palpable goiter and by RIAs of Tg, T3, rT3, T4, and TSH in sera from 441 women (48-53 yr old), representing a normal population included in a study on the prevalence of thyroid disease. Smoking habits were evaluated by a questionnaire, and the women were then classified as never smokers (n = 192), smokers (n = 169), and exsmokers (n = 80). Smokers were subdivided as moderate (1-19 cigarettes/day) and heavy (greater than or equal to 20 cigarettes/day). Palpable goiter was found in 15% of the smokers, in contrast to only 4% of the exsmokers and 9% of the never smokers. Among smokers, 37% had serum Tg values over 30 micrograms/liter (third quartile), while such values were found in only 16% of the exsmokers and 18% of the never smokers. In addition, smokers were found to have higher serum T3 and lower rT3 concentrations than never smokers; this difference was most pronounced in heavy smokers. Serum T4 was not different, while TSH was insignificantly lower in smokers than in nonsmokers. Exsmokers did not differ significantly from never smokers in any of these parameters. It seems possible that cigarette smoking may have two, calorigenically opposed, effects on thyroid hormone production; it may be goitrogenic (possibly due to inhaled thiocyanate), but it may also enhance the formation of T3 at the expense of rT3 formation.

Reduced breast cancer mortality in women under age 50: updated results from the Malmö Mammographic Screening Program.

This article provides additional follow-up data of two cohorts from the Malmö Mammographic Screening Trial (MMST). The first cohort, MMST I, contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932. Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988. The second cohort, MMST II, contained 17,786 women born between 1933 and 1945. Fifty four percent of these women were randomly invited to screening between 1978 and 1990. The remaining 46%--the control group--was invited to screening between 1991 and 1994. Nine screening rounds were completed in MMST I, and a mean of five rounds were completed in MMST II; the screening interval ranged from 18 to 24 months. The effect of screening on breast cancer mortality was assessed by pooling the two cohorts. At the end of follow-up--December 1993 for MMST I and December 1995 for MMST II--there was a statistically significant 36% reduction in breast cancer mortality in the intervention groups (relative risk = 0.64; 95% CI: 0.45-0.89; P = 0.009). A harm-benefit analysis showed, however, that for every two breast cancer deaths prevented, one clinically insignificant cancer was diagnosed; for each breast cancer death prevented, 63 cancer-free women had been called back for further examinations; and for every 20 lives saved, one radiation-induced breast cancer death may have occurred. Recommendations for screening must therefore weigh mortality benefits against these negative effects.

Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity.

BACKGROUND: Previous studies of associations between diet, obesity, and blood concentrations of alpha-tocopherol and beta-carotene have been equivocal. Furthermore, most studies used only body mass index (BMI) as an obesity measure. OBJECTIVES: Our objectives were to examine the associations between energy and nutrient intakes, alcohol consumption, tobacco use, and serum cholesterol and serum concentrations of alpha-tocopherol and beta-carotene, and to examine the associations between different measures of general and central adiposity and serum concentrations of alpha-tocopherol and beta-carotene. DESIGN: This was a cross-sectional, population-based study of 253 men and 276 women aged 46-67 y. Nutrient data were collected by a modified diet history method. Measures of obesity included BMI, percentage of body fat (impedance analysis), waist-to-hip ratio, and waist circumference. The associations between serum nutrient concentrations and the other factors were examined by multiple linear regression. RESULTS: Twenty-one percent of men and 34% of women used antioxidant supplements. The mean BMI was 26.1 in men and 25.4 in women. Serum beta-carotene concentration was positively associated with serum cholesterol concentration, fiber intake, and beta-carotene intake, and negatively associated with smoking and all measures of obesity. In men, serum beta-carotene concentration was not significantly associated with central adiposity after adjustment for body fat. Serum alpha-tocopherol concentration was positively correlated with serum cholesterol, obesity, and vitamin E intake. In women, serum alpha-tocopherol concentration was also positively associated with intakes of ascorbic acid and selenium. Serum alpha-tocopherol concentration was associated with central adiposity after adjustment for body fat. CONCLUSION: Serum beta-carotene and alpha-tocopherol concentrations have different associations with diet, smoking, general adiposity, and central adiposity.