AimsOrthostatic 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 resultsProspective 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.ConclusionOrthostatic 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.

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.

Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, ␣1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38 -50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.

The large proportion (64%) of the population with risk factors for cardiovascular disease and the substantially (5-12-fold) increased IHD mortality in those risk groups, calls for actions aimed at preventing premature IHD deaths. Such action should include measures directed towards the whole population and comprehensive treatment programmes for high-risk individuals, including intervention to stop smoking. The substantial overlap between risk factors calls for one high-risk clinic caring for all risk groups.

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, ␣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 (Ϯ2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Key Words: inflammation Ⅲ hypertension Ⅲ epidemiology C ross-sectional data have shown positive associations between blood pressure and different markers of inflammation. [1][2][3][4][5] The causal significance of this association is unclear. Some researchers have suggested that hypertension may promote inflammation. 2 Others have reported that the leukocyte count, a widely accepted marker of inflammation, is associated with the development of hypertension. 6 However, whether inflammation-sensitive plasma proteins (ISPs) are risk factors for the development of hypertension is largely unknown.We have previously reported that elevated levels of ISPs (ie, orosomucoid, ␣1-antitrypsin, fibrinogen, haptoglobin, and ceruloplasmin) are associated with an increased incidence of cardiovascular diseases and that cardiovascular risk substantially increases if several of these proteins are elevated. 7 The reason for this relationship is poorly understood. The present study explored the hypothesis that future blood pressure increase is associated with ISP levels. Methods Study CohortBetween 1974 and 1983, 22 444 men participated in a screening program for the detection of individuals at high risk for cardiovascular diseases. 8 The participation rate was 71%. Plasma proteins were determined in 30% of the cohort, which was randomly selected. Complete information on 5 ISPs was available in 6193 men (mean age 46.8Ϯ3.7 years, range 28 to 61 years). Men with a history of myocardial infarction, stroke, cancer, and men undergoing treatment for hypertension (according to questionnaire) were excluded.Between 1991 and 1996, approximately 40% of all 45-to 73 year-old men in the city of Malmö were examined as a part of the Malmö Diet and Cancer study. 9 A total of 2262 men were reexamined. Figure summarizes the exclusions and drop-outs from the original cohort. Age at baseline ranged between 35 and 50 years. Mean follow-up was 15.7Ϯ2.2 years (range 9.5 to 21.5).All men with medical treatment for hypertension at baseline were excluded. Men with treatment for hypertension at follow-up were included in the analysis of incidence of hypertension and blood pressure treatment. However, they were excluded from analyses of blood pressure increase (Figure).Of the 5791 healthy men who were not receiving medication for hypertension at baseline, 42...

This study explores the relationship of inflammationsensitive plasma proteins (ISPs) with the prevalence of diabetes and the interrelationships between ISPs and diabetes in the prediction of death and incidence of myocardial infarction and stroke. Plasma levels of fibrinogen, ␣1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were assessed in 6,050 men, aged 28 -61 years. All-cause and cardiovascular mortality and incidence of myocardial infarction and stroke were monitored over 18.7 ؎ 3.7 years. Prevalence of diabetes (n ‫؍‬ 321) was significantly associated with ISP levels among overweight and obese men but not among men with BMI <25 kg/m 2 . The association was similar for insulin resistance according to homeostasis model assessment. High ISP levels (two or more ISPs in the top quartile) increased the cardiovascular risk among diabetic men. The risk factor-adjusted relative risks for cardiovascular mortality, myocardial infarction, and stroke were 2.8 (CI 1.8 -4.5), 2.2 (1.5-3.2), and 2.5 (1.4 -4.6), respectively, for diabetic men with high ISP levels (reference: nondiabetic men with low ISP levels). The corresponding risks for diabetic men with low ISP levels were 1.8 (1.1-3.0), 1.3 (0.8 -2.1), and 1.2 (0.6 -2.5), respectively. In conclusion, in this populationbased cohort, diabetes was associated with increased ISP levels among overweight and obese men but not among men with normal weight. High ISP levels increased the cardiovascular risk similarly in diabetic as compared with nondiabetic men. Diabetes 52:442-447, 2003 D iabetes and impaired glucose tolerance have been associated with increased plasma concentrations of various inflammation-sensitive plasma proteins (ISPs), including fibrinogen, haptoglobin, ␣1-antitrypsin, serum amyloid A, C-reactive protein, and orosomucoid (1-6). Prospective studies have reported associations among various markers of inflammation and incidence of diabetes (7-10), and it has been proposed that inflammation has a causal role for the development of diabetes (4). In particular, inflammatory cytokines formed in the adipose tissue are associated with glucose dysregulation (4,11-13). However, the joint effect of overweight and inflammation on the prevalence of diabetes has not been studied extensively in the general population. Whether prevalence of diabetes shows similar relationships with ISPs in lean and obese subjects is largely unknown.Many prospective studies have reported relationships between moderately increased plasma concentrations of ISPs and increased incidences of myocardial infarction and stroke (14 -17). It is now widely accepted that inflammation has a role in the development of atherosclerosis. Diabetes is another risk factor for myocardial infarction and stroke (18 -20). The relationships between diabetes and other traditional cardiovascular risk factors, e.g., an adverse lipid profile, obesity, hypertension, and physical inactivity, cannot completely explain the increased risk in diabetic individuals (18). Even though it has been suggested that infla...

A noninvasive method based on high-resolution B-mode ultrasonography and a computerized image-analyzing system were used for the quantification of early (thickening of the intimamedia complex) and late (plaque) atherosclerosis in the carotid and the femoral artery. The difference between repeated measurements was assessed to estimate intraobserver and interobserver differences. The results were satisfactory, with a coefficient of variation for measurement of lumen diameter in the common carotid artery of 3.8±4.1% (r=0.91) and for the femoral artery of 4.8±4.1% (r=0.93). Corresponding figures for intima-media thickness in the common carotid artery and the femoral artery were 10.0±8.5% (r=0.86) and 16.2+12.6% (r=0.91), respectively. The coefficient of variation for measurements of maximal intima-media thickness at the site of the plaque was 14.6±10.5% (r=0.88); for plaque base, 13.1 ±9.0% (r=0.91); and for plaque area, 16J± 12.6% (r=0.90). The method seems promising for the detection and quantification of early and late atherosclerotic lesions in the carotid and femoral arteries. (Arteriosclerosis and Thrombosis 1992;12:261-266) I t has been possible to study the extent of atherosclerosis mainly by identifying clinical symptoms or by analyzing morbidity and mortality caused by vascular events. Symptoms and vascular events are, however, signs of advanced vascular disease and, as such, are not useful for studies of the asymptomatic phase of atherosclerosis.In the clinical situation, the extent of atherosclerosis has been evaluated by angiography, but for ethical reasons, this method cannot be used for serial investigations of atherosclerotic lesions in an asymptomatic population. Furthermore, results from other studies suggest that so long as the atherosclerotic process occupies less than 40% of the cross-sectional area inside the internal elastic layer, the artery may dilate to keep its lumen diameter intact, at least in the coronary arteries. Received December 20,1990; revision accepted October 23,1991. diminishes the usefulness of angiography for detection of early atherosclerotic lesions, as this method only visualizes the lumen of the vessel. During the past few years, several groups have attempted to develop noninvasive (ultrasonographic) methods to measure the thickness of the arterial wall.3 -7 Duplex-scanning estimations of the degree of stenosis have been correlated to those on angiograms and to findings in specimens obtained at thrombendarterectomy.8 Studies of intima-media thickness, as determined by high-resolution B-mode ultrasonography and light microscopy, have been done on autopsy material 3 and in animal models, 7 and these show good correlation. The usefulness of this method is substantiated by findings that show that patients with hypercholesterolemia have a thicker intima-media layer than do those with normal serum cholesterol levels. 9 The change in intima-media thickness has also been found to be associated with other risk factors for atherosclerosis.10 Reproducibility concerning the method...

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, ␣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 (Ͻ120, 120 to 139, Ն140 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 Ն140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP Ն140 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 Ͻ120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP Ն140 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. (Stroke.