Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.

BACKGROUND: A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking. METHODS AND RESULTS: We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0). CONCLUSION: Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise.

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension

Doppler echocardiographic indexes and 24-h ambulatory blood pressure data in sedentary middle-aged men presenting exaggerated blood pressure response during dynamical exercise test.

Previous studies have pointed out that exaggerated blood pressure (BP) response during physical exercise could be an early marker of essential hypertension. Apparently some of the exaggerated BP responders present changes in the heart geometry and function that are usually found in the early course of the hypertensive disease. To evaluate the association between exaggerated BP response and these changes, we submitted 20 normotensive men presenting elevated BP response during bicycle exercise (hyperreactive group, systolic BP > or = 220 mmHg at maximal workload) to 24-h ambulatory blood pressure monitoring (ABPM) and to two-dimensionally guided M-mode echocardiography and pulsed Doppler. The results from this group were contrasted with those of a comparable group, which otherwise, presented normal BP response during the same procedure (control group, systolic BP < or = 210 mmHg at maximal workload). The ABPM measurements were normal and analogous between the two groups: the mean 24-h systolic blood pressure (SBP) was respectively 126 +/- 6 mmHg and 129 +/- 5 mmHg, diastolic blood pressure (DBP) 82 +/- 4 mmHg in both groups, and heart rate (HR), respectively 76 +/- 9 and 74 +/- 7 bpm. The univariate correlation (R) between the maximal BP response during bicycle exercise and BP measurements in the ABPM were in general weak, and as a whole, the hyperreactive group presented the weakest correlation coefficients. M-mode echocardiographic data such as the left ventricular mass index (LVMI, 80 +/- 10 vs. 81 +/- 11 g/m2), posterior wall and interventricular septal thickness (PWT, 8.8 +/- 0.6 vs. 8.6 +/- 0.7 mm; IVST, 9.0 +/- 0.4 vs. 8.8 +/- 0.6) were also normal and comparable between the groups. LV systolic functional indexes such as fractional shortening (LVFS, 39 +/- 2.8 vs. 40 +/- 3.5%) and ejection fraction (LVEF, 70 +/- 3.5 vs. 71 +/- 3.7%) were also normal and similar. Doppler-derived LV diastolic functional indexes such as the peak velocity of early flow divided by the peak velocity of late flow (RE/A) and isovolumetric relaxation time (IVRT) were also equivalent (RE/A, both 1.3 +/- 0.2, IVRT 79 +/- 7 vs. 81 +/- 6 msec). These results support the concept that an exaggerated BP elevation during physical activity, when not accompanied of higher levels of BP during daily activities are not associated with changes in the heart geometry or in the ventricular function, and might represent an hemodynamical behavior of limited pathological and clinical importance. These conclusions must be taken cautiously since personal characteristics such as life style, family history of hypertension, gender, race and also the levels of BP chosen to delimit a normal and an exaggerated BP response might be important factors determining the consequences of the hyperreactive behavior.

Noninvasive ambulatory 24-hour blood pressure in patients with high normal blood pressure and exaggerated systolic pressure response to exercise.

Few studies have investigated the significance of abnormal increases in systolic pressure during exercise in patients with high normal blood pressure and its correlation with 24-hour ambulatory blood pressure monitoring and left ventricular structure. This study was performed in 30 sedentary subjects (42 +/- 4 years old) with high normal blood pressure. Fifteen subjects presenting < 220 mm Hg systolic pressure during ergometric exercise were compared with 15 others with systolic pressure > or = 220 mm Hg. Average 24-hour (systolic, 127 +/- 5 versus 142 +/- 4 mm Hg, P < .01; diastolic, 82 +/- 4 versus 92 +/- 3 mm Hg, P < .01), daytime (systolic, 130 +/- 6 versus 144 +/- 4 mm Hg, P < .01; diastolic, 84 +/- 4 versus 92 +/- 4 mm Hg, P < .01), and nighttime (systolic, 116 +/- 7 versus 132 +/- 6 mm Hg, P < .01; diastolic, 72 +/- 6 versus 85 +/- 6 mm Hg, P < .01) ambulatory blood pressure monitoring values were significantly higher in subjects with an exaggerated blood pressure response to exercise. No significant differences were observed in left ventricular morphology. These findings indicate that subjects presenting high normal blood pressure and exaggerated systolic pressure during exercise show significantly high ambulatory blood pressure monitoring values that are not associated with left ventricular hypertrophy.