C-reactive protein (CRP) associated with risk of coronary heart disease, stroke, vascular mortality, and death from several cancers and lung disease

Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people.

This Lancet meta-analysis included records of 160,309 people without a history of vascular disease from 54 long-term prospective studies.

Risk ratios (RRs) were 1·23 for coronary heart disease; 1·32 for ischaemic stroke; 1·34 for vascular mortality; and 1·34 for non-vascular mortality.

CRP concentration has continuous associations with the risk of:

- coronary heart disease
- ischaemic stroke
- vascular mortality
- death from several cancers and lung disease

The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.

Is is still a topic of debate is whether CRP has a causal role in the development of cardiovascular disease.

However, even if CRP might not be involved in the causal pathway of atherogenesis and plaque rupture, it may still be a valuable tool in cardiovascular medicine.

In primary prevention, lovastatin therapy was more cost effective in people with increased CRP concentrations.

The JUPITER trial recently showed that, in people with relatively normal LDL cholesterol concentrations and CRP higher than 2 mg/L, rosuvastatin reduced cardiovascular risk. Even if CRP turns out to be not directly causal in cardiovascular disease, it might be useful to identify individuals at cardiovascular risk and to evaluate the efficacy of our preventing and therapeutic interventions.

References:
C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. The Lancet, Volume 375, Issue 9709, Pages 132 - 140, 9 January 2010.
C-reactive protein and cardiovascular risk: more fuel to the fire. S Matthijs Boekholdt a b, John JP Kastelein b. The Lancet, Volume 375, Issue 9709, Pages 95 - 96, 9 January 2010.

C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease - BMJ, 2011. http://goo.gl/d5lCH
Image source: C-reactive protein. Wikipedia, GNU Free Documentation License.

Glycated hemoglobin as a diagnostic test for diabetes predicts mortality more accurately than fasting glucose

Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose.

The glycated hemoglobin value at baseline was associated with newly diagnosed diabetes and cardiovascular outcomes.

For glycated hemoglobin, values of less than 5.0%, 5.0-5.5%, 5.5-6.0%, 6.0-6.5%, and 6.5% or greater, the hazard ratios for diagnosed diabetes were 0.52, 1.00, 1.86, 4.48, and 16.47, respectively.

For coronary heart disease, the hazard ratios were 0.96, 1.00, 1.23, 1.78, and 1.95, respectively. The hazard ratios for stroke were similar.

In contrast, glycated hemoglobin and death from any cause were found to have a J-shaped association curve.

The association between the fasting glucose levels and the risk of cardiovascular disease or death from any cause was not significant.

In this community-based population of nondiabetic adults, glycated hemoglobin was associated with a risk of diabetes and more strongly associated with risks of cardiovascular disease and death from any cause as compared with fasting glucose. These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes.

References:

Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults. NEJM, 2010.

Image source: OpenClipArt.org, public domain.

Short telomeres lead to chromosomal instability and increased cancer risk and mortality

Telomeres are essential to preserve the integrity of the genome. Critically short telomeres lead to replicative cell senescence and chromosomal instability and may thereby increase cancer risk.

Leukocyte telomere length was measured by quantitative polymerase chain reaction in 787 participants free of cancer at baseline in 1995 from a prospective, population-based study in Italy. The follow-up period was 10 years.

Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.

11.7% of participants developed cancer (incidence rate, 13.3 per 1000 person-years).

Short telomere length at baseline was associated with incident cancer independently of cancer risk factors (hazard ratio [HR] 1.60).

Compared with participants in the longest telomere length group, the HR for incident cancer was 2.15 in the middle length group and 3.11 in the shortest length group. Furthermore, short telomere length was associated with cancer mortality and individual cancer subtypes with a high fatality rate.

There is an inverse relationship between telomere length and both cancer incidence and mortality.

References:
Telomere Length and Risk of Incident Cancer and Cancer Mortality. Peter Willeit, MD; Johann Willeit, MD; Agnes Mayr, MD; Siegfried Weger, MD; Friedrich Oberhollenzer, MD; Anita Brandstätter, PhD; Florian Kronenberg, MD; Stefan Kiechl, MD. JAMA. 2010;304(1):69-75.

Aspirin 75 mg daily reduces incidence and mortality due to colorectal cancer

High-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects (bleeding) might limit its potential for long-term prevention. The long-term effectiveness of lower doses (75-300 mg daily) is unknown. This study in The Lancet assessed the effects of aspirin on incidence and mortality due to colorectal cancer over 20 years.

In the four trials of aspirin versus control (mean duration of treatment 6 years), 2·8% of 14,000 patients had colorectal cancer during a follow-up of 18 years.

Aspirin reduced the 20-year risk of colon cancer (incidence hazard ratio [HR] 0·76, but not rectal cancer (0·90).

Where subsite data were available, aspirin reduced risk of cancer of the proximal colon (0·45), but not the distal colon (1·10). Benefit increased with duration of treatment - aspirin taken for 5 years or longer reduced risk of proximal colon cancer by 70% and also reduced risk of rectal cancer (0·58).

There was no increase in benefit at doses of aspirin greater than 75 mg daily. However, risk of fatal colorectal cancer was higher on 30 mg versus 283 mg daily.

Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. Benefit was greatest for cancers of the proximal colon, which are not otherwise prevented effectively by screening with sigmoidoscopy or colonoscopy.

References:
Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. The Lancet, Volume 376, Issue 9754, Pages 1741 - 1750, 20 November 2010.

Image source: Colon (anatomy), Wikipedia, public domain.