Psychosocial work characteristics and perceived control in relation to cardiovascular rewind at night.

This study examined the effects of psychosocial work characteristics on cardiovascular rewind at night. Ambulatory 24-hr recordings of blood pressure (BP) and heart rate (HR) of 75 borderline hypertensive and 74 normotensive men were related to diary ratings of perceived control (PC) and to scores of psychological demand (P), control (C), and social support (S) at work determined by an occupational classification system. Multiplicative interaction terms for job strain (P x C), isostrain (P x C x S), and Job Strain x Perceived Control (P x C x PC) were calculated. The P x C x PC interaction predicted diastolic BP at night but not at work. A delayed latency to attain the lowest systolic BP during the night was found for jobs with high job strain and isostrain. Low perceived control and social support were associated with higher HR at work and at night. A logistic regression analysis indicated that the interaction between P x C x PC and the body mass index was independently associated with borderline hypertension.

Circulating heat shock protein 60 is associated with early cardiovascular disease.

The phylogenetically conserved nature of heat shock proteins (Hsp) has led to the proposition that they may provide a link between infection and the inflammatory component to vascular disease. Hypertension is associated with atherosclerosis. Here, we measured circulating heat shock protein and heat shock protein antibody levels in association with borderline hypertension. Seventy-two men with borderline hypertension patients and 75 normotensive control subjects (diastolic blood pressure 85 to 94 and <80 mm Hg, respectively) were selected from a population-screening program. The levels of Hsp60; Hsp70; and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibodies were determined with enzyme immunoassay. The presence of carotid atherosclerosis and the intima-media thickness values were determined with ultrasonography. A major novel observation in this report was the detection of circulating Hsp60, which was present at a significantly enhanced level in patients with borderline hypertension. Furthermore, serum Hsp60 was associated with intima-media thicknesses (P<0.01). Anti-Hsp65 antibody levels were higher in borderline hypertension (P<0.001), whereas Hsp70 and anti-Hsp70 antibody levels did not differ. In contrast to anti-Hsp65 antibody, anti-Hsp60 antibody levels were lower in borderline hypertension (P<0.03), although the difference was quantitatively small. None of the parameters evaluated were associated with atherosclerosis, metabolic factors, or smoking. We identified elevated Hsp60 levels in patients with borderline hypertension and an association between early atherosclerosis and Hsp60 levels. The physiological role of Hsp60 release has yet to be defined, but given the proinflammatory properties, these proteins could be involved in the induction/progression of both hypertension and atherosclerosis, as well as being markers for early cardiovascular disease.

Antibodies to platelet-activating factor are associated with borderline hypertension, early atherosclerosis and the metabolic syndrome.

OBJECTIVE: Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes and endothelial cells, and PAF can be retained in activated endothelial cell membranes. Furthermore, PAF-like lipids are produced in other phospholipid membranes as in oxidized LDL. Atherosclerosis is a chronic inflammation in the artery wall, but little is known about the role of immune reactions in the early stages of development of cardiovascular disease. In the present study we investigated if there are antibodies to PAF (aPAF) that may play a role in borderline hypertension and early atherosclerosis. DESIGN: Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure 85-94 and <80 mmHg, respectively) were recruited from a population screening programme. Antibody levels were determined by use of ELISA. Carotid intima-media (IM)-thickness and atherosclerosis was determined by B-mode ultrasonography. RESULTS: BHT men had 49.3% higher aPAF levels of IgG class than NT controls (P = 0.0007). Antibodies to the biologically inactive lysoPAF did not differ between BHT and NT group. aPAF levels were associated with IM-thickness in the left (P = 0.02) and right (P = 0.009) carotid artery. Furthermore, aPAF levels were enhanced in individuals with the metabolic syndrome (n = 44) as compared to those without (n = 102; P = 0.009), and also significantly associated with insulin levels (P = 0.02) and insulin resistance (P = 0.02). CONCLUSIONS: aPAF antibodies may reflect early vascular changes and thus serve as novel markers for disease, and they may also be pathogenic, by eliciting an inflammatory reaction in the vascular wall.

A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.

BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.

Autoantibodies to OxLDL are decreased in individuals with borderline hypertension.

-Elevated antibody levels to oxidized low-density lipoprotein (aOxLDL) have been shown to correlate with the degree of atherosclerosis in some studies. On the other hand, immunization of experimental animals with OxLDL, leading to enhanced aOxLDL levels, inhibits the development of the disease. The role of antibodies to OxLDL during different stages of disease development is thus not clear. The objective of this study was to determine the level of aOxLDL in early cardiovascular disease, such as borderline hypertension (BHT). Seventy-three men with BHT were matched with 75 age-matched normotensive (NT) men (diastolic blood pressures, 85 to 94 and <80 mm Hg, respectively). Antibody levels to epitopes of OxLDL were determined by use of conventional and chemiluminescence ELISA techniques. Presence of carotid atherosclerosis was determined by B-mode ultrasonography; atherosclerotic plaques were detected in 29 individuals. BHT men had significantly lower aOxLDL levels of IgG class (P=0.001) and IgM class (P=0.001) than NT controls, as determined using chemiluminescence ELISA. Similar results were obtained using conventional ELISA, with which aOxLDL of IgG (P=0. 0002) and IgM (P=0.026) classes and antibody levels to malondialdehyde-LDL were significantly lower in BHT individuals. There was no difference in antibody levels between individuals with or without carotid atherosclerosis. It is not clear whether the decreased aOxLDL levels in BHT are due to a decreased immune reaction to OxLDL or to an increased consumption of aOxLDL due to binding to early atherosclerotic lesions. The possible implications of these findings are discussed.

Increased blood pressure reactivity in children of borderline hypertensive fathers.

OBJECTIVE: To evaluate the influence of heredity on blood pressure levels and reactivity in the offspring of borderline hypertensive and normotensive fathers. PARTICIPANTS AND OUTCOME MEASURES: Borderline hypertensive and normotensive men having normotensive wives (n = 25 and 26) were identified in a population screening program. Their children aged above 12 years were invited to participate. Seventeen having a borderline hypertensive father (BHT+) and 19 with a normotensive father (NT+) were investigated. Clinical and 24 h ambulatory blood pressure was measured, as well as blood pressure reactivity to an arithmetic mental stress test. RESULTS: The BHT+ group had a significantly higher clinical systolic blood pressure than the NT+ group (126 +/- 13 versus 115 +/- 7 mmHg, P< 0.01) but similar 24 h blood pressure levels. Systolic blood pressure variability (standard deviation of systolic blood pressure measurements each hour over 24 h) was significantly higher in the BHT+ group (18 +/- 4 versus 16 +/- 4 mmHg, P< 0.05). During mental stress test the BHT+ group had significantly higher increases in systolic and diastolic blood pressures at 4 min (NT+ 8% and 13% versus BHT+ 16% and 23% above baseline, P< 0.05) and significantly elevated DBP during the period after the stress test (NT+ 1% versus BHT+ 13% above baseline, P < 0.01). CONCLUSION: Even a mild level of hypertensive heredity affects important markers of blood pressure regulation, such as blood pressure variability and reactivity to mental stress. This might have prognostic implications; it also points to the possible importance of these variables as early signs of a familial predisposition to hypertension.

Antibodies to endothelial cells in borderline hypertension.

BACKGROUND: Antibodies to endothelial cells (aECs) and to cardiolipin (aCLs) are implicated in autoimmune diseases like systemic lupus erythematosus vasculitis. Beta2-Glycoprotein 1 (beta2GP1) is a cofactor for aCLs. The present study investigated the possible role of aECs, aCLs, and abeta2GP1 in borderline hypertension. METHODS AND RESULTS: Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure, 85 to 94 and <80 mm Hg, respectively) were recruited from a population screening program. Antibody levels were determined by ELISA. Presence of carotid atherosclerosis was determined by B-mode ultrasonography, and 29 individuals had atherosclerotic plaques. BHT men had significantly higher aEC and abeta2GP1 levels of IgG class than NT control subjects (P=0.029 and P=0.0001, respectively). aEC levels of IgM class were higher in BHT (P=0.012), but not abeta2GP1 levels. There was no correlation between aCL levels and BHT. Individuals with atherosclerotic plaques had significantly higher aEC levels of both IgG (P=0.042) and IgM subclasses (P=0.018) than those without plaques, but no difference was found in aCL and abeta2GP1 levels. Endothelin and aECs of IgM class were significantly associated. CONCLUSIONS: We demonstrate the first evidence of a significant elevation of aEC and abeta2GP1 levels in borderline hypertension. These findings provide a new link between hypertension and atherosclerosis and indicate that humoral immune reactions to the endothelium may play an important role in both conditions.

Insulin-like growth factor binding protein-1 as a marker of the metabolic syndrome--a study in borderline hypertension.

AIM: To evaluate insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) in borderline hypertension (BHT) in relation to plasma lipoprotein and insulin levels, anthropometric variables and 24-h ambulatory blood pressure (BP). Seventy-five BHT men diastolic BP (DBP) 85-94 mmHg) and 75 age-matched normotensive controls (NT, DBP < or = 80 mmHg) were recruited from a population-based screening program. RESULTS: There was no difference in IGF-I or IGFBP-1 between BHT and NT men. However, subjects with insulin resistance (IR) had decreased levels of IGF-1 (145 +/- 36 vs 153 +/- 28 microg/L, p < 0.05) and IGFBP-1 (41 +/- 15 vs 52 +/- 20 microg/L, p < 0.01) compared to those without IR. IGF-I correlated inversely to BP levels in the BHT group (r = -0.24 to -0.28, p < 0.05). IGFBP-1 correlated inversely with BMI, lipoprotein and insulin levels (r = -0.29 to -0.48, p < 0.01), independent of IR. CONCLUSION: While there are no differences between BHT and NT men in IGF-I and IGFBP-1, both are significantly decreased in IR subjects. IGFBP-1 exhibits a close correlation to metabolic factors. Decreased IGFBP-1 could thus be suggested as a variable marking the "metabolic syndrome" of hypertension.

The dopaminuric response to high salt diet in insulin-dependent diabetes mellitus and in family history of hypertension.

Alterations in the renal dopamine [DA] system have been suggested to contribute to the development of hypertension and diabetic nephropathy. To identify early abnormalities in renal handling of DA and sodium we challenged 16 normotensive patients with uncomplicated insulin-dependent diabetes (IDDM), 18 normotensive nondiabetic subjects with familial borderline hypertension, and 16 healthy controls, 14-29 years old, with a high-sodium diet (HSD). Systolic blood pressure was slightly higher in subjects with familial borderline hypertension than in the other groups on a normal sodium diet (NSD) (P < 0.05). Blood pressure and 24-h urinary measurements were performed on a NSD and after 3 days on a HSD. Twenty-four-hour urinary DA excretion was similar in all groups on NSD. A significant rise in DA excretion was noted after HSD in control subjects (P < 0.01), but not in subjects with a family history of hypertension or with IDDM. Urinary sodium excretion increased in all groups. A correlation between the change in DA and sodium/creatinine ratio after HSD was seen in healthy controls (r = 0.57, P = 0.02) but not in those with familial borderline hypertension (r = 0.18, P = 0.47) or with IDDM (r = 0.40, P = 0.15). A rise in systolic (but not diastolic) pressure was noted only in the IDDM group after HSD (P = 0.02). In conclusion, an impairment in the renal DA and sodium system can be detected early in IDDM and in individuals with familial hypertension. We speculate that this impairment may contribute to the development of hypertension and microvascular disease in both conditions.

Association of serum antibodies to heat-shock protein 65 with borderline hypertension.

Heat-shock proteins protect cells from damage but are also often the target of immune responses in inflammation and may therefore both induce and perpetuate the chronic inflammation characterizing atherosclerosis. Hypertension is a well-established risk factor for atherosclerosis, and recently, borderline hypertension also has been related to atherosclerosis. The present study investigated the possible role of heat-shock proteins in borderline hypertension and their relation to atherosclerosis by investigating antibody titers against the 65-kD heat-shock protein (HSP65). Sixty-six men with borderline hypertension and 67 age-matched normotensive men (diastolic pressure, 85 to 94 and < 80 mm Hg, respectively) were recruited from a population screening program. Titers of antibodies to HSP65 were determined by enzyme-linked immunosorbent assay. The presence of carotid atherosclerosis was determined by B-mode ultrasonography. Twenty-seven individuals had atherosclerotic plaques: 48 were smokers (more than one to two cigarettes per day). Borderline hypertensive men had higher anti-HSP65 reactivity than normotensive control subjects (P = .034). Smokers with atherosclerosis had low levels of antibodies to HSP65 compared with nonsmokers with atherosclerosis (P = .002). Furthermore, when high-risk individuals (borderline hypertension plus plaque, n = 15) were compared with matched low-risk individuals (normotensive with no plaque, n = 15), the high-risk men had significantly enhanced antibody titers to HSP65 (P = .041). In conclusion, we demonstrate that serum antibody titers to HSP65 are enhanced in individuals with borderline hypertension, which may indicate an ongoing immune reaction in the artery wall.

Stress-induced laboratory blood pressure in relation to ambulatory blood pressure and left ventricular mass among borderline hypertensive and normotensive individuals.

Our primary aim in the present study was to investigate the association between blood pressure measured in the laboratory and in the ambulatory state in a group of middle-aged borderline hypertensive men and age-matched normotensive control subjects. In addition, we examined the relation between stress-induced blood pressure measurements and left ventricular mass. Blood pressure and heart rate were measured noninvasively during a standardized laboratory stress protocol and four times per hour throughout 24 hours. Borderline hypertensive subjects had significantly higher systolic and diastolic pressures than normotensive subjects during both the daytime (systolic pressure, 141.1 +/- 9.7 versus 130.9 +/- 8.6 mm Hg; diastolic pressure, 88.8 +/- 7.0 versus 79.4 +/- 6.2 mm Hg, P < .001) and nighttime (systolic pressure, 114.0 +/- 9.9 versus 107.1 +/- 8.3 mm Hg; diastolic pressure, 71.5 +/- 7.5 versus 64.6 +/- 7.2 mm Hg, P < .001). The borderline hypertensive group also displayed increased systolic pressure reactivity in the laboratory compared with the normotensive group. The groups did not differ significantly in left ventricular mass (index). In both borderline hypertensive and normotensive individuals, blood pressure levels during stress testing were closely related to ambulatory blood pressure levels (r = .51 to .82). Furthermore, stress-induced blood pressure levels were significantly correlated to left ventricular mass in borderline hypertensive (r = .33 to .40) but not normotensive subjects. Since stress-induced blood pressure levels were significantly associated with both ambulatory blood pressure levels and left ventricular mass in borderline hypertensive subjects, the addition of standardized stress testing to casual blood pressure measurements may improve risk estimation.

Elevation of plasminogen activator inhibitor 1 in borderline hypertension is linked to concomitant metabolic disturbances.

In the present study we investigated plasma levels of plasminogen activator inhibitor 1 (PAI-1), fibrinogen and von Willebrand factor (vWF) in borderline hypertensive (BHT) men [diastolic blood pressure (DBP) 85-94 mmHg, n = 75] and age-matched normotensive (NT) control subjects (DBP < or = 80 mmHg, n = 75), in relation to smoking, body mass index (BMI) and fasting lipoprotein and insulin levels. PAI-1 levels were elevated in the BHT group [16.3 vs. 13.7 arbitrary units (AU), P = 0.032], whereas levels of fibrinogen and vWF were similar in the two groups. The PAI-1 elevation was even more pronounced in dyslipidaemic BHT subjects than in normolipidaemic NT subjects (20.0 vs. 10.3 arbitrary units (AU), P = 0.001). PAI-1 levels showed strong correlations with insulin, lipoproteins and BMI (P < 0.01-0.001), but not with DBP. The results show that disturbances in the fibrinolytic system appear even in borderline hypertension. The elevation of PAI-1 levels seems to be more strongly linked to concomitant metabolic disturbances than to blood pressure levels.

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension.

OBJECTIVES: To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. DESIGN: A case-control study. SUBJECTS: Borderline hypertensive men (diastolic blood pressure (DBP) 85-94 mmHg, n = 69) and age-matched normotensive controls (DBP < or = 80 mmHg, n = 69) from a population screening programme. MAIN OUTCOME MEASURES: Echocardiography (M-mode), insulin (RIA) and 24-APBM (Del Mar P-IV) levels. RESULTS: The borderline group showed a significant increase in septal thickness (10.4 +/- 1.5 vs. 9.7 +/- 1.5 mm, P < 0.01), peak systolic wall stress (218 +/- 38 vs. 202 +/- 38 10(3) dynes cm-2, P < 0.05) and a decrease in LV ejection time (28.4 +/- 2.5 vs. 29.5 +/- 2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13 +/- 0.14 vs. 1.06 +/- 0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22-0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34-0.47, P < 0.01) but not the borderline, group. CONCLUSIONS: Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.

Carotid intima-media thickness and plaque in borderline hypertension.

BACKGROUND AND PURPOSE: In this study, we investigated intima-media thickness and plaque occurrence in the carotid arteries of men with borderline hypertension compared with that in normotensive control subjects and investigated the relations of these variables to atherosclerotic risk factors. METHODS: Using B-mode ultrasonography, we compared carotid artery intima-media thickness and plaque occurrence in men with borderline hypertension (diastolic blood pressure of 85 to 94 mm Hg, n = 73) with that in age-matched normotensive control subjects (diastolic blood pressure of 80 mm Hg, n = 72). We evaluated the relationships of intima-media thickness and plaque occurrence to atherosclerotic risk factors such as age, smoking, lipoprotein levels, and fasting insulin levels. RESULTS: The borderline hypertensive group exhibited a slight increase in overall intima-media thickness (0.73 versus 0.69 mm, P = .07), which was most evident in the right carotid artery (0.72 versus 0.67 mm, P < .05). There were more borderline hypertensive subjects with plaque (26% versus 16%, NS), again more evident on the right side (18% versus 6%, P < .05). Age and high-density lipoprotein cholesterol were consistently related to intima-media thickness (t = 1.94 to 3.24 and t = -2.25 to -2.69, respectively, P < .05), whereas age was the only significant determinant for plaque/nonplaque (F = 6.4, P < .05). In addition, there was a significant difference in intima-media thickness between the right and left carotids, irrespective of group (F = 4.43, P < .05). CONCLUSIONS: Our results indicate that vascular structural changes occur even in borderline hypertension, although this seems more related to general atherosclerotic risk factors than to blood pressure alone. Additionally, a possible difference in the development of atherosclerotic lesions of the left and right carotid arteries is suggested, emphasizing the importance of measuring and reporting values from both sides when studying carotid intima-media thickness and plaque occurrence.

Dyslipoproteinemic changes in borderline hypertension.

The present study examined plasma lipoprotein, lipoprotein lipase, hepatic lipase, and insulin levels in men with borderline hypertension (diastolic blood pressure 85 to 94 mm Hg) compared with age-matched normotensive control subjects (diastolic blood pressure less than or equal to 80 mm Hg, n = 75 + 75). High-density lipoprotein (HDL) subclasses were determined in a subset (n = 45 + 45). While total and low-density lipoprotein cholesterol levels were similar, levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides (0.46 versus 0.41 mmol/L, P = .027, and 1.0 versus 0.85 mmol/L, P = .031) and total triglycerides (1.53 versus 1.33 mmol/L, P = .009) were elevated and HDL cholesterol was reduced in the borderline group compared with the normotensive group (1.17 versus 1.26 mmol/L, P = .043). The HDL subclass HDL2b concentration was lower (0.16 versus 0.24 mmol/L, P = .006), while HDL3b and HDL3c concentrations were higher in the borderline group (0.38 versus 0.32 mmol/L, P = .016, and 0.19 versus 0.16 mmol/L, P = .042). Significantly higher activities of hepatic lipase in the borderline group (282 versus 232 mU/mL, P = .024) and significant correlations between lipoprotein lipase activity and VLDL and HDL concentrations suggest an involvement of these enzymes in the development of these differences. When adjusted for body mass index or insulin level, all differences disappeared, except for HDL3b and HDL3c concentrations, which remained significantly elevated. These results indicate that dyslipoproteinemic changes are present in early hypertension. Although most of these changes are related to obesity, alterations in HDL profile were not explained by influences of body mass index and insulin.