Publications

BACKGROUND

Cardiovascular disease (CVD) is now a leading cause of death in HIV-infected persons; however, risk markers for CVD are ill defined in this population. We examined the association between longitudinal measures of kidney function and albuminuria with risk of atherosclerotic CVD and heart failure in a contemporary cohort of HIV-infected individuals.

METHODS AND RESULTS

We followed a national sample of 17 264 HIV-infected persons receiving care in the Veterans Health Administration for (1) incident CVD, defined as coronary, cerebrovascular, or peripheral arterial disease, and (2) incident heart failure. Rates of CVD and heart failure were at least 6-fold greater in the highest-risk patients with an estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m(2) and albuminuria > or =300 mg/dL versus those with no evidence of kidney disease (eGFR > or =60 mL/min per 1.73 m(2) and no albuminuria). After multivariable adjustment, eGFR levels 45 to 59, 30 to 44, and <30 mL/min per 1.73 m(2) were associated with hazard ratios for incident CVD of 1.46 (95% confidence interval, 1.15 to 1.86), 2.03 (1.47 to 2.82), and 1.99 (1.46 to 2.70) compared with eGFR > or =60 mL/min per 1.73 m(2). Similarly, albuminuria levels 30, 100, and > or =300 mg/dL had hazard ratios for CVD of 1.28 (1.09 to 1.51), 1.48 (1.15 to 1.90), and 1.71 (1.30 to 2.27) compared with absent albuminuria. The associations between eGFR and albuminuria with heart failure were larger in magnitude and followed the same trends.

CONCLUSIONS

In this national sample of HIV-infected persons, eGFR and albuminuria levels were strongly associated with risk of CVD and heart failure. Kidney function and albuminuria provide complementary prognostic information that may aid CVD risk stratification in HIV-infected persons.

Carbohydrate response element binding protein (ChREBP) is a recently discovered transcription factor whose levels and activity are increased by glucose leading to the activation of target genes, which include acetyl-CoA carboxylase, fatty acid synthase, and liver-type pyruvate kinase. Here, we demonstrate that lipopolysaccharide (LPS) treatment causes a marked decrease in ChREBP mRNA and protein levels in the liver of mice fed a normal chow diet or in mice fasted for 24 h and then re-fed a high carbohydrate diet. This decrease occurs rapidly and is a sensitive response (half-maximal dose 0.1 μg/mouse). The decrease in ChREBP is accompanied by a decrease in the expression of ChREBP target genes. Zymosan and turpentine treatment also decrease hepatic ChREBP levels and the expression of its target genes. Additionally, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) decrease liver ChREBP expression both in vivo and in Hep3B cells in culture. Finally, LPS decreased ChREBP expression in muscle and adipose tissue. These studies demonstrate that ChREBP is down-regulated during the acute phase response resulting in alterations in the expression of ChREBP regulated target genes. Thus, ChREBP joins a growing list of transcription factors that are regulated during the acute phase response.

BACKGROUND

Distal coronary artery disease (CAD) is less amenable to surgery or stenting compared with proximal disease. However, little is known about the epidemiology of distal versus proximal CAD.

METHODS

We determined the prevalence and factors associated with proximal, mid, and distally located plaque in the left anterior descending, left circumflex, and right coronary arteries in 418 subjects without prior CAD history who underwent coronary computed tomographic angiography for symptoms or stress test results. Clinical characteristics and coronary artery calcium (CAC) scores were also determined.

RESULTS

Most subjects (88%) had plaque, but only 18% of plaques were associated with stenosis >50%. In subjects with single-vessel plaque, only 7% had distal plaque, whereas 75% had proximal plaque. With 3-vessel plaque, 70% had distal and 100% had proximal plaques. Of subjects with a single location of plaque along a vessel, most had proximal plaque (69%); isolated distal-vessel plaque was rare (2%). Distal plaque was dominantly found in association with both proximal and mid plaque (88%). After multivariable adjustment for demographics, traditional, and nontraditional risk factors, both increasing number of vessels with plaque and clinically significant CAC scores were independently associated with higher odds of distal plaque, whereas associations of traditional risk factors were weaker. Distal plaque was independently associated with stenosis > 50%.

CONCLUSION

These data support the concept that early lesions are most often proximal and that CAC scoring may be a poor screening tool for detecting proximal disease. Furthermore, distal lesions are more associated with advanced disease than with traditional cardiovascular risk factors.