An estimated 21 million Americans have diabetes and 284,000 die from it each year. A total of 65% of the deaths are related to cardiovascular causes. Type 2 diabetes increases the risk for heart disease by two to four times.
The ACCORD study set out to investigate the effects of lowering Type 2 diabetes patients’ blood glucose levels to those found in nondiabetic patients (hemoglobin [Hb]A1c goal level of below 6%) to determine whether this reduces cardiovascular mortality. The HbA1c levels attained by diabetics in the USA are approximately 7–7.9%.
The study enrolled 10,250 patients between the ages of 40 and 80 years at particularly high risk for heart attack and stroke. Of these, 257 in the intensive-treatment, compared with 203 in the standard-treatment arms, died. However, the death rates were lower than those found in similar populations in other studies.
“A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these especially high risk patients with Type 2 diabetes,” said Elizabeth G Nabel, Director of the The US National Heart, Lung, and Blood Institute (NHLBI), organizers of the study. “Though we have stopped this part of the trial, we will continue to care for these participants, who now will receive the less-intensive standard treatment. In addition, we will continue to monitor the health of all participants, seek the underlying causes for this finding, and carry on with other important research within ACCORD.”
Extensive analyses by ACCORD researchers have not determined a specific cause for the increased deaths among the intensive treatment group. Based on ana-lyses conducted to date, there is no evidence that any medication or combination of medications is responsible.
The researchers will continue to monitor participants and conduct additional analyses to try and explain the findings.
Source: www.nhlbi.nih.gov
Genetic tolerance to colder climates may predispose to metabolic syndrome
Humans adapted to living in colder climates tend to be bulkier, with shorter arms and legs, thus having an increased BMI. Now, however, scientists from the University of Chicago (IL, USA) have discovered a strong correlation between climate and genetic variations that seem to influence the metabolic syndrome, both positively and negatively.
As our ancestors migrated from Africa to cooler areas there was a selection pressure for heat production and retention characteristics. Anna Di Rienzo, Professor of Human Genetics at the University of Chicago, said that, now, “in an era that combines widespread central heating with an overabundant food supply, those genetic alterations have taken on a different sort of significance. They alter our susceptibility to a whole new set of diseases, such as obesity, coronary artery disease and Type 2 diabetes.”
The researchers studied genetic variation in 1034 people from 54 populations, finding widespread correlations between the frequencies of certain genetic variations and colder climates.
“The biological processes that influence tolerance to climatic extremes are likely to play important roles in the pathogenesis of common metabolic disorders,” the authors conclude, “…our results argue for a role of climate adaptations in the biological processes underlying the metabolic syndrome and its phenotypes.”
Sources: news.uchicago.edu; Hancock AM, Witonsky DB, Gordon AS et al. Adaptations to climate in candidate genes for common metabolic disorders. PLoS Genet. 4(2), e32 doi :10.1371/journal.pgen.0040032 (2008).
Research shows link between low vitamin D and heart risk
The Harvard Medical School (MA, USA) researchers found that individuals with the lowest level of vitamin D had a 62% increased chance of suffering from cardiovascular problems compared to those with the highest blood vitamin D levels. Study author Thomas J Wang, an assistant professor of medicine at Harvard Medical School, believes it is too early to recommend routine supplementation and that there is still not enough evidence to put vitamin D deficiency on the same level as high cholesterol and other known risk factors.
“It is probably premature to consider vitamin D in the same light as those risk factors because this is one of the first clinical studies,” Wang said. “We don’t know whether increasing vitamin D levels with some kind of supplement decreases risk. That would require some kind of trial.”
Vitamin D is already known to be essential to strong bones, as it facilitates the uptake of calcium. Vitamin D can be obtained from sunlight, for example 1 h, of which, per week is thought to produce approximately 30 ng/l of blood, which is sufficient to prevent rickets. Black-skinned individuals are thought to need longer than white-skinned due to pigmentation that reduces the production of the vitamin. It can also be obtained from fortified milk and oily fish. Current US recommendations are for a daily intake of 200 international units (IU) for young, 400 IU for midde-aged and 600 IU for elderly people.
Getting sufficient vitamin D from these sources can be difficult, especially for elderly people in the winter months. Robert U Simpson, a professor of pharmacology at the University of Michigan, whose group was the first to identify vitamin D receptors in heart cells also believes the recommended levels are actually still too low. “People should get at least 1000 IU, perhaps 2000,” he said. “I take 1000 IU a day. I recommend that intake right now as part of a multivitamin supplement.”
Wang is much more cautious. He does not take any vitamin supplement, but concedes that the 600 IU recommended daily intake for older people is “very, very difficult to achieve, especially in winter in northern parts of the country…Virtually all elderly people have to take supplements.”
The incidence of cardiovascular events for people with low vitamin D levels and high blood pressure was double that of people with higher blood levels of vitamin D. “The question becomes how much data such as ours is needed to justify a controlled trial,” Wang said. “The answer is, more than we have now.”
Source: Wang TJ, Pencina MJ, Booth SL et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation (2008) (Epub ahead of print).
Grant awarded to advance diagnosis for acute kidney injury
The 5-year grant will fund the study of new diagnostic techniques to speed the detection of acute kidney injury (AKI) in cardiac surgery patients. AKI is a common complication that can arise following cardiac surgery and causes increased mortality from this procedure. The current diagnostic technique, using serum creatinine, is slow; results from this test are usually normal until 2–3 days after cardiac surgery. The Yale researchers will study three alternative biomarkers: urine IL-18, urine neutrophil gelatinase associated lipocalin (NGAL) and serum cystatin C. They are hoping these biomarkers will give a more accurate and rapid detection compared with serum creatinine, enabling much earlier diagnosis of the occurrence of postoperative AKI – within 24–48 h.
“Having new biomarkers to replace serum creatinine will allow for the early and accurate diagnosis of AKI” said nephrologist Chirag Parikh, who will be leading the team.
The work will be carried out in conjunction with a clinical consortium of investigators, the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI). This consortium will study urine samples, serum samples and clinical data from 1800 hospitalized patients under-go-ing cardiac surgery. By comparing the timing of the increases in biomarkers with the clinical diagnosis of AKI, they hope to identify a biomarker that gives a more rapid detection of this disorder. This biomarker(s) may also prove useful in the rapid detection of other conditions. “Findings from this study will pave the way for larger multicenter studies of these biomarkers in other clinical conditions, and for clinical trials to prevent or treat AKI.” Parikh commented.
Source: Yale School of Medicine: www.yale.edu
Nanothin coating ‘hides’ artery stent
A new stent with a nanothin surface coating that ‘hides’ the stent from the body’s immune system shows great promise in the treatment of blocked arteries, according to a new study. Crucially, the superthin coating appears to avoid the potentially lethal clotting problems caused by the drug-eluting stents (DES) being used to treat plaque-clogged arteries at present.
Stents have been used to open up blocked arteries in the heart and elsewhere in the body since the mid-1990’s. However, following transplantation of a traditional stent, the body identifies it as a foreign object and overreacts to it accordingly. This brings about a scarring process that can cause the vessels to reclog – a process termed restenosis.
DES, aimed at combating the problem of restenosis, came into use 4 years ago. Although restenosis rates dropped dramatically following their introduction, research has shown that the chemotherapeutic agent used to coat the devices can interfere with the blood vessel’s healing process. There is an increased risk of a blood clot forming inside the stent and causing a heart attack.
Researchers estimate that DESs kill upwards of 1,000 people each year. To counteract the problem of thrombosis, it is recommended that patients receiving DES are placed on dual antiplatelet therapy for at least 1 year. “Although antiplatelet therapy delays the problem of thrombosis in DES, when the therapy is stopped, the problem returns,” said Corrado Tamburino, principal investigator of the study. “However, continuing on antiplatelet therapy indefinitely is problematic, too, because it increases the risk of bleeding, and may prevent future surgeries.”
Recently, a new stent has been designed to overcome this dilemma. The stent is coated with a superthin layer of poly[bis(trifluroexthoxy)phosphazene], or Polyzene®-F, a surface treatment comparable to Teflon® or silicone. In contrast, Polyzene-F is 15-times slicker than Teflon and is only approximately 40 nm thick, making it 25,000-times thinner than human hair and too thin to be seen with a traditional microscope. Essentially, the coating conceals the stent so that the body’s immune system does not react to it as a foreign object. This promotes the healing process as the stent is more readily incorporated into the body. Furthermore, because the coating is a medically inert chemical compound, rather than a drug, it ought to circumvent the problem of thrombosis associated with DES.
The results of the first use of this surface-treated stent in humans are being presented at the 20th annual International Symposium on Endovascular Therapy (ISET). The 6-month follow-up information is available for 40 of the 55 patients who received the new stent and the results look promising; despite antiplatelet therapy being discontinued at 30 days, no patients have developed thrombosis to date and restenosis rates are low. “Our preliminary research suggests that this polymer-coated stent is a very promising solution to restenosis and thrombosis” said Tamburino.
Source: Tamburino C. Assessment of the Latest Non-Thrombogenic Angioplasty (ATLANTA) Stent Study: Preliminary Results. Presented at: The 20th Annual International Symposium on Endovascular Therapy (ISET). FL, USA, 20–24 January, 2008.
Off-label DES fair better than BMS in practice
Experience at Wake Forrest University School of Medicine (NC, USA) suggests that patients who receive a drug-eluting stent (DES) for ‘off-label’ indications have a reduced risk for nonfatal myocardial infarction and death in the following 2 years compared to patients receiving a bare-metal stent (BMS).
In order to investigate proposed safety concerns with regard to the use of DESs implanted off-label, 1164 consecutive patients who received BMS in the year before the introduction of DES and 1285 consecutive patients who received DES after these stents became fully available, were compared.
The study published in the Journal of the American College of Cardiology found that 530 (22%) of the overall population met criteria for on-label stent use and the remaining 78% were off-label procedures. Stents were used for off-label indications in 75% of the BMS and 80% of the DES procedures.
At 2 years, the risks for target vessel revascularization, nonfatal myocardial infarction or death, and all-cause mortality were lower using DES compared with BMS in the overall population, at a hazard ratios of 0.62, 0.77 and 0.71, respectively.
The authors conclude: “The observations of lower cumulative rates of non-fatal MI and all-cause mortality at 2 years in DES-treated patients compared with BMS-treated patients in spite of a low incidence of late DES thrombosis is reassuring that use of DES in routine practice is safe.”
Source: Applegate RJ, Sacrinty MT, Kutcher MA et al. “Off-label” stent therapy 2-year comparison of drug-eluting versus bare-metal stents. J. Am. Coll. Cardiol. 51, 607–614 (2008).
Beetroot juice may reduce blood pressure
The key ingredient that is responsible for the observed antihypertensive effect appears to be nitrate, which is also present in green, leafy vegetables. The research suggests that drinking beetroot juice, or including other nitrate-rich vegetables into the diet, might be an easy and low-cost approach to the prevention and treatment of hypertension and cardiovascular disease.
Hypertension is the underlying cause of 50% of coronary heart disease and approximately 75% of strokes. Currently, over 25% of the global adult population are hypertensive, a figure which looks set to rise to 29% by the year 2025.
It is well-known that diets rich in fruit and vegetables reduce blood pressure (BP) but exactly how they achieve this has not yet been fully elucidated. Until now, the protective effects of vegetable-rich diets have primarily been attributed to their antioxidant vitamin content. This new study proposes a new candidate, dietary nitrate, as underlying the cardiovascular health benefits demonstrated by such diets.
Healthy volunteers were given beetroot juice to drink and their BP levels were measured at intervals throughout the ensuing 24 h. Interestingly, the study found that BP levels were reduced within an hour of drinking the juice, BP reduction was even more pronounced after 3–4 h and a degree of reduction continued to be observed for up to 24 h.
The authors hypothesize that the observed effects are a consequence of beetroot juice containing a high level of nitrate and thus being a good source of vasoprotective nitric oxide (NO). They explain that approximately 25% of the nitrate consumed by humans is reduced to nitrite by anerobic bacteria on the surface of the tongue. After swallowing, some of this nitrite is reduced, in the acidic environment of the stomach, to NO. Alternatively, the nitrite re-enters the circulation where it can be reduced to NO at a later time. The theory that the authors propose is supported by other findings from their study; changes in BP levels after drinking beetroot juice were inversely correlated with plasma nitrite levels and, significantly, no drop in BP was recorded in participants who refrained from swallowing their saliva during, and for 3 h after, drinking the juice.
This new study suggests that consuming nitrate-rich vegetables could be a drug-free, simple and cost-effective approach to tackle the modern day problem of rising blood pressure.
Although the results of this preliminary study are certainly promising, more research needs to be conducted in order to ascertain whether dietary nitrate is effective at reducing high blood pressure in a sustained manner over a prolonged period of time.
Sources: Webb AJ, Patel N, Loukogeorgakis S et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension Feb 4 [Epub ahead of print] (2008); Barts and The London School of Medicine: www.smd.qmul.ac.uk