Because decreases in the ratio of myocardial insoluble to soluble collagen parallel LV dilatation in rats, reductions in myocardial collagen cross-linking may be an important mechanism contributing to LV dilatation in heart disease.

These results demonstrate that diabetes mellitus can produce a stiff myocardium before the development of myocardial fibrosis. The stiff myocardium in the early stages of the development of the cardiomyopathy of diabetes mellitus is not a consequence of an increase in ventricular resistance afterload and in these circumstances is associated with the formation of collagen AGEs.

An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

One or more, high-quality single visit nurse-recorded auscultatory BP measurements may be equally as effective as ambulatory BP in predicting target organ damage in a population sample of African ancestry.

Abstract-Although central pulse pressure (PPc) is strongly related to central mean arterial pressure (MAPc), PPc predicts cardiovascular outcomes beyond MAPc. Whether modifiable risk factors for hypertension contribute to PPc and its determinants, independent of MAPc, is uncertain. In 635 randomly recruited participants, we assessed the independent relationship between 24-hour urinary sodium (Na ϩ ) or potassium (K ϩ ) excretion and brachial artery PP (in office or 24-hour; nϭ487), PPc, the forward (P1) and augmented (Paug) pressure wave components of PPc, central augmentation index, and determinants of central pressure waves, including aortic pulse wave velocity, effective reflecting distance, and reflective wave transit time. Central dynamics were determined using applanation tonometry of the carotid, femoral, and radial arteries. With adjustments for potential confounders, urinary Na ϩ /K ϩ was independently associated with in-office, central, and 24-hour PP, as well as Paug, P1, and central augmentation index (PϽ0.05 to PϽ0.005). With further adjustments for MAPc (or diastolic BP), urinary Na ϩ /K ϩ was independently associated with PPc, 24-hour PP, Paug, P1, and central augmentation index (PϽ0.05 to Pϭ0.005) but not with in-office PP, pulse wave velocity, effective reflecting distance, or reflective wave transit time. In conclusion, in a population of African ancestry, urinary salt excretion is independently related to central and 24-hour PP independent of MAPc or diastolic BP, effects that are attributed to increases in both P1 and Paug but not to pulse wave velocity. Hence, modifying salt intake could influence cardiovascular risk through effects on 24-hour and central PPs, as well as P1 and Paug, independent of steady-state pressure (MAP or diastolic BP) or pulse wave velocity. (Hypertension. 2010;56:584-590.) Key Words: pulse pressure Ⅲ arterial stiffness Ⅲ central blood pressure Ⅲ salt intake P ulse pressure (PP) predicts cardiovascular outcomes beyond other measures of blood pressure (BP), including measures of steady-state pressure, such as mean arterial pressure (MAP). [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Moreover, central PP may be more closely associated with cardiovascular outcomes than peripheral PP. [15][16][17][18][19] Thus, contemporary notions of the adverse actions of BP are viewed in terms of steady-state effects, indexed by MAP, and dynamic or pulsatile effects, indexed by PP, with central PP receiving the most attention. The effects of PP independent of MAP on cardiovascular outcomes 1-14 are particularly impressive considering the close relationship between MAP and PP. Developing strategies that decrease PP, particularly central PP, without necessarily influencing MAP, is, therefore, of considerable interest, and in this regard understanding the mechanisms responsible for these changes is of importance. Although aging has been identified as the major determinant of PP, with increases in both the augmented and the forward pressure wave contributing to central PP, 20 -23 the im...

Collagen cross-linking may determine the diverse relation that exists between increases in myocardial collagen concentrations and either myocardial stiffness or chamber remodelling in hypertension. These findings support the notion that fibrosis contributes to myocardial stiffness as well as LV dilatation in LVH, albeit an effect that is modulated by collagen quality.

We assessed the myocardial susceptibility to ischemic-reperfusion injury in obese rat hearts in the absence and the presence of predicted circulating concentrations of insulin and fatty acids. Feeding rats a high-calorie diet resulted in increases in body weight, visceral fat content, cardiac hypertrophy, plasma insulin, nonesterified free fatty acid, and triglyceride concentrations. In the absence of both insulin and fatty acids in the coronary perfusate, the hearts of obese rats developed an increased infarct size (41.9 +/- 1.9% for obese vs. 22.9 +/- 2.3% for control, P < 0.05) and a reduced percent recovery of aortic output (4.2 +/- 4.2% for obese vs. 27.7 +/- 3.4% for controls, P < 0.05) after coronary artery occlusion and reperfusion. In the presence of insulin in the coronary perfusate, a cardioprotective effect was noted in both groups, an action that was greater in hearts from obese compared with control rats and which abolished the obesity-induced changes in infarct size (13.8 +/- 1.2% for controls vs. 21.0 +/- 1.6% for obese), and percent recovery of aortic output (60.2 +/- 4.7% for controls vs. 45.7 +/- 9.4% for obese). Fatty acids (0.7 mM, control; and 1.5 mM, obese) added to the coronary perfusate with in vivo concentrations of insulin dramatically increased infarct size (48.2 +/- 3.1% for obese, and 37.5 +/- 2.7% for control; P < 0.05 vs. without fatty acids) and decreased percent aortic output recovery (control, 10.4 +/- 5.2%, and obese 7.8 +/- 3.5%; P < 0.05 vs. without fatty acids) in both groups to similar values. In conclusion, in obesity, the impact of an increased susceptibility of the myocardium to ischemic-reperfusion injury on myocardial injury is likely to be overshadowed by the comparatively greater roles played by predicted increases in circulating insulin and fatty acids found in vivo. These data support the notion that adiposity per se is unlikely to be a valuable predictor of outcomes in ischemic-reperfusion injury.

In a population sample with a high prevalence of obesity, excess adiposity promotes concentric, rather than eccentric LV geometric changes, effects which are independent of conventional, central artery or 24-h BP measured on a single occasion.