Elevated dietary sodium intake exacerbates myocardial hypertrophy associated with cardiac-specific overproduction of angiotensin II

Introduction/hypothesis
Cardiac hypertrophy is an independent risk factor predictive of cardiovascular disease and is significantly associated with morbidity and mortality. The mechanism by which angiotensin II (Ang II) and dietary sodium exert additive effects on the development of cardiac hypertrophy is unclear. The goal of this study was to evaluate the hypothesis that, where there is a genetic predisposition to Ang II-dependent hypertrophy, there is also an increased susceptibility to sodium-induced hypertrophy mediated by AT₁-receptor expression.

Methods
Diets of low sodium (LS, 0.3% w:w) and high sodium (HS, 4.0% w:w) content were fed to adult (age 25 weeks) control wild-type mice (WT) and to weeks) control wild-type mice (WT) and to transgenic mice exhibiting cardiac specific overexpression of angiotensinogen (TG). At the conclusion of a 40-day dietary treatment period, cardiac tissue weights were compared and the relative expression levels of Ang II receptor subtypes (AT_1A and AT₂) were evaluated using RT-PCR.

Results
WT and TG mice fed HS and LS diets maintained comparable weight gains during the treatment period. The normalised heart weights of TG mice were elevated compared to WT, and the extent of the increase was greater for mice maintained on the HS diet treatments (WT 12% vs. TG 41% increase in cardiac weight index). While a similar pattern of growth was observed for ventricular tissues, the atrial weight parameters demonstrated an additional significant effect of dietary sodium intake on tissue weight, independent of animal genetic type. No differences in the relative (GAPDH normalised) expression levels of AT_1A- and AT₂-receptor mRNA were observed between diet or animal genetic groups.

Conclusion
This study demonstrates that, where there is a pre-existing genetic condition of Ang II-dependent cardiac hypertrophy, the pro-growth effect of elevated dietary sodium intake is selectively augmented. In TG and WT mice, this effect was evident with a relatively short dietary treatment intervention (40 days). Evaluation of the levels of Ang II receptor mRNA further demonstrated that this differential growth response was not associated with an altered relative expression of either AT_1A- or AT₂-receptor subtypes. The cellular mechanistic bases for this specific Ang II-dietary sodium interaction remain to be elucidated.

Pro-inflammatory dietary intake as a risk factor for CVD in men: a 5-year longitudinal study

Convincing evidence has identified inflammation as an initiator of atherosclerosis, underpinning CVD. We investigated (i) whether dietary inflammation, as measured by the 'dietary inflammatory index (DII)', was predictive of 5-year CVD in men and (ii) its predictive ability compared with that of SFA intake alone. The sample consisted of 1363 men enrolled in the Geelong Osteoporosis Study who completed an FFQ at baseline (2001-2006) (excluding participants who were identified as having previous CVD). DII scores were computed from participants' reported intakes of carbohydrate, micronutrients and glycaemic load. DII scores were dichotomised into a pro-inflammatory diet (positive values) or an anti-inflammatory diet (negative values). The primary outcome was a formal diagnosis of CVD resulting in hospitalisation over the 5-year study period. In total, seventy-six events were observed during the 5-year follow-up period. Men with a pro-inflammatory diet at baseline were twice as likely to experience a CVD event over the study period (OR 2·07; 95 % CI 1·20, 3·55). This association held following adjustment for traditional CVD risk factors and total energy intake (adjusted OR 2·00; 95 % CI 1·03, 3·96). This effect appeared to be stronger with the inclusion of an age-by-DII score interaction. In contrast, SFA intake alone did not predict 5-year CVD events after adjustment for covariates (adjusted OR 1·40; 95 % CI 0·73, 2·70). We conclude that an association exists between a pro-inflammatory diet and CVD in Australian men. CVD clinical guidelines and public health recommendations may have to expand to include dietary patterns in the context of vascular inflammation.