TUGAS PRAKTIKUM NON BIOMEDIK: LITERATURE SEARCHING :

PRISMA & LIMA ABSTRAK

41160012 IKA IRMAWATI SUSANTO

41160080 SERAPINA AOLINA SAYU
41160079 JOSEPH IZMARDHA COUTEAU
41160069 REYNALDY VALENTINO P.MARPAUNG
41160068 GEORGIUS GREGAH GUMILAR
41160024 DOMINICUS BINTANG MAHARDHIKA J
41160047 DEWA KETUT KARTIKA PUTRA
41160055 DATU ANDRA S.D. SAMPETODING
41160100 GUSTI AGUNG SINTA SHAKUNTALA
41160071 DANNY SHAN VEDA
41160015 FERREN FANTRIZHA

UNIVERSITAS KRISTEN DUTA WACANA

YOGYAKARTA
2018
PRISMA GENERATOR: Hubungan HBA1c, stroke, diabetes, umur,sex
(Rawshani et al., 2018)

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
Rawshani A1, Rawshani A1, Franzén S1, Sattar N1, Eliasson B1, Svensson AM1, Zethelius B1,
Miftaraj M1, McGuire DK1, Rosengren A1, Gudbjörnsdottir S1.

Abstract

BACKGROUND:

Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general
population. We investigated whether the excess risk of death and cardiovascular events among
patients with type 2 diabetes could be reduced or eliminated.

METHODS:

In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the
Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of
age, sex, and county. We assessed patients with diabetes according to age categories and
according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-
density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox
regression was used to study the excess risk of outcomes (death, acute myocardial infarction,
stroke, and hospitalization for heart failure) associated with smoking and the number of variables
outside target ranges. We also examined the relationship between various risk factors and
cardiovascular outcomes.

RESULTS:

The median follow-up among all the study participants was 5.7 years, during which 175,345
deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased
stepwise for each risk-factor variable within the target range. Among patients with diabetes who
had all five variables within target ranges, the hazard ratio for death from any cause, as compared
with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute
myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95
(95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among
patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients
with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest
predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death.

CONCLUSIONS:

Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared
to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the
general population. (Funded by the Swedish Association of Local Authorities and Regions and
others.).

Bibliography

Rawshani, A. A., Rawshani, A. A., Franzén, S., Sattar, N., Eliasson, B., Svensson, A.-M., …
Gudbjörnsdottir, S. (2018). Risk Factors, Mortality, and Cardiovascular Outcomes in
Patients with Type 2 Diabetes. The New England Journal of Medicine, 379(7), 633–644.
https://doi.org/10.1056/NEJMoa1800256
(Zhao et al., 2014)

Sex differences in the risk of stroke and HbA(1c) among diabetic patients.
Zhao W1, Katzmarzyk PT, Horswell R, Wang Y, Johnson J, Hu G.
Abstract
AIMS/HYPOTHESIS:

Sex differences in macrovascular disease, especially in stroke, are observed across studies of
epidemiology. We studied a large sample of patients with type 2 diabetes to better understand the
relationship between glycaemic control and stroke risk.

METHODS:

We prospectively investigated the sex-specific association between different levels of HbA(1c)

and incident stroke risk among 10,876 male and 19,278 female patients with type 2 diabetes.

RESULTS:

During a mean follow-up of 6.7 years, 2,949 incident cases of stroke were identified. The
multivariable-adjusted HRs of stroke associated with different levels of HbA(1c) at baseline
(HbA(1c) <6.0% [<42 mmol/mol], 6.0-6.9% [42-52 mmol/mol] [reference group], 7.0-7.9% [53-
63 mmol/mol], 8.0-8.9% [64-74 mmol/mol], 9.0-9.9% [75-85 mmol/mol] and ≥10.0% [≥86
mmol/mol]) were 0.96 (95% CI 0.80, 1.14), 1.00, 1.04 (0.85, 1.28), 1.11 (0.89, 1.39), 1.10 (0.86,
1.41) and 1.22 (0.92, 1.35) (p for trend = 0.66) for men, and 1.03 (0.90, 1.18), 1.00, 1.09 (0.94,
1.26), 1.19 (1.00, 1.42), 1.32 (1.09, 1.59) and 1.42 (1.23, 1.65) (p for trend <0.001) for women,
respectively. The graded association between HbA(1c) during follow-up and stroke risk was
observed among women (p for trend = 0.066). When stratified by race, whether with or without
glucose-lowering agents, this graded association of HbA(1c) with stroke was still present among
women. When stratified by age, the adjusted HRs were significantly higher in women older than
55 years compared with younger women.

CONCLUSIONS/INTERPRETATION:

The current study suggests a graded association between HbA1c and the risk of stroke among
women with type 2 diabetes. Poor control of blood sugar has a stronger effect in diabetic women
older than 55 years.

Bibliography

Zhao, W., Katzmarzyk, P. T., Horswell, R., Wang, Y., Johnson, J., & Hu, G. (2014). Sex
differences in the risk of stroke and HbA(1c) among diabetic patients. Diabetologia, 57(5),
918–926. https://doi.org/10.1007/s00125-014-3190-3
(Andersson et al., 2012)

Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause
mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes.
Andersson C1, van Gaal L, Caterson ID, Weeke P, James WP, Coutinho W, Finer N, Sharma
AM, Maggioni AP, Torp-Pedersen C.
Author information
Erratum in

 Diabetologia. 2012 Oct;55(10):2860. Couthino, W [corrected to Coutinho, W].

Abstract
AIMS/HYPOTHESIS:

The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in
obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was
therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes
(SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or
cardiovascular disease.

METHODS:

HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke,
resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using
Cox regression models.

RESULTS:

Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA(1c)
available at baseline (i.e. study randomisation). Median age was 62 years (range 51-86 years),
median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were women. The median HbA(1c)
concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150 mmol/l]) and median diabetes duration
was 7 years (0-57 years). For each 1 percentage point HbA(1c) increase, the adjusted HR for the
primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12
for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than
in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA(1c) increase (p
= 0.02 for interaction). There was no evidence of increased risk associated with HbA(1c) ≤ 6.4%
(≤ 46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of
cardiovascular disease did not modify the associations.

CONCLUSIONS/INTERPRETATION:

In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA(1c)

concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-
cause mortality.
Bibliography

Andersson, C., van Gaal, L., Caterson, I. D., Weeke, P., James, W. P. T., Coutinho, W., … Torp-
Pedersen, C. (2012). Relationship between HbA1c levels and risk of cardiovascular adverse
outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women
and men with type 2 diabetes. Diabetologia, 55(9), 2348–2355.
https://doi.org/10.1007/s00125-012-2584-3
(Cederholm et al., 2009)

Effect of tight control of HbA1c and blood pressure on cardiovascular diseases in type 2 diabetes:
an observational study from the Swedish National Diabetes Register (NDR).
Cederholm J1, Zethelius B, Nilsson PM, Eeg-Olofsson K, Eliasson B, Gudbjörnsdottir S;
Swedish National Diabetes Register.
Collaborators (6)
Author information
Abstract
AIM:

To estimate hazard ratio (HR) of first incident fatal/non-fatal cardiovascular diseases (CVD) in
female/male type 2 diabetic patients, with tight versus adverse control of HbA1c and blood
pressure (BP) at baseline, age 30-70 years, no baseline CVD, followed for mean 5.7 years.

METHODS:

2593 patients with tight control of HbA1c <7.5% and BP < or = 140/90 mmHg (median
6.5%/130/80 mmHg), and 2160 patients with adverse control 7.5-9.0%/141-190/91-110 mmHg
(median 8.1%/155/85 mmHg).

RESULTS:

The hazard ratio (HR) for CVD with tight/adverse control was 0.67 (0.55-0.80; p<0.001),
adjusting for age, sex, duration, hypoglycaemic treatment, smoking, BMI, lipid-lowering drugs,
antihypertensive drugs, microalbuminuria. Adjusted HR for myocardial infarction, coronary heart
disease, stroke and total mortality were 0.72 (0.56-0.92; p=0.01), 0.69 (0.55-0.86; p<0.001), 0.62
(0.45-0.84; p<0.001), 1.00 (0.72-1.39). The partial population-attributable risk percent for
myocardial infarction, stroke and CVD was 23%, 33%, 29% if adverse HbA1c/BP control could
be avoided, while 43%, 38%, 39% with overweight and smoking also avoided. Baseline lower
BMI and absence of microalbuminuria were associated with tight control.

CONCLUSION:

Median difference of HbA1c/BP 1.6%/25/5 mmHg between tight and adverse control
considerably reduced the risk of cardiovascular diseases. The findings call for a multi-factorial
approach to improve HbA1c, BP, obesity, smoking, and microalbuminuria.

BIBLIOGRAPHY

Cederholm, J., Zethelius, B., Nilsson, P. M., Eeg-Olofsson, K., Eliasson, B., Gudbjörnsdottir, S.,
& Swedish National Diabetes Register. (2009). Effect of tight control of HbA1c and blood
pressure on cardiovascular diseases in type 2 diabetes: an observational study from the
Swedish National Diabetes Register (NDR). Diabetes Research and Clinical Practice,
86(1), 74–81. https://doi.org/10.1016/j.diabres.2009.07.003
(Metcalf, Kyle, Kenealy, & Jackson, 2017)

HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at

baseline.
Metcalf PA1, Kyle C2, Kenealy T3, Jackson RT4.
Author information
Abstract
AIMS:

We compared the utility of glycated hemoglobin (HbA1c) and oral glucose tolerance (oGTT) in
non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease
(CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes
microvascular complications.

METHODS:

Data from a New Zealand community setting were prospectively linked to hospitalization,
mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior
laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or
CVD event), there were 31,148 adults who had an HbA1c and 2-h 75g oGTT. HbA1c was
measured by ion-exchange high-performance liquid chromatography, and glucose using a
commercial enzymatic method. We compared glycemic measures and outcomes using
multivariable Cox proportional hazards regression.

RESULTS:

The median follow-up time was 4years (range 0 to 13). The mean age was 57·6years and 53·0%
were male. After adjusting for other glycemic measures (fasting glucose, 2-h glucose and/or
HbA1c where relevant) in addition to age, sex, ethnicity and smoking habit, the hazard ratios for
incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h
glucose levels, followed by HbA1c and lastly by fasting glucose. However, all-cause mortality
and CHD were significantly associated with HbA1c concentrations only, and ischemic stroke and
CVD events with 2-h glucose only. Circulatory complications showed a stronger association with
HbA1c.

CONCLUSION:
Apart from neuropathy, HbA1c showed stronger associations with outcomes compared to fasting
glucose and provides a convenient alternative to an oGTT
Bibliography
Metcalf, P. A., Kyle, C., Kenealy, T., & Jackson, R. T. (2017). HbA1c in relation to incident
diabetes and diabetes-related complications in non-diabetic adults at baseline. Journal of
Diabetes and Its Complications, 31(5), 814–823.
https://doi.org/10.1016/j.jdiacomp.2017.02.007
Kumpulan semua Daftar Pustaka:
Andersson, C., van Gaal, L., Caterson, I. D., Weeke, P., James, W. P. T., Coutinho, W., … Torp-Pedersen, C.
(2012). Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-
cause mortality in overweight and obese cardiovascular high-risk women and men with type 2
diabetes. Diabetologia, 55(9), 2348–2355. https://doi.org/10.1007/s00125-012-2584-3
Cederholm, J., Zethelius, B., Nilsson, P. M., Eeg-Olofsson, K., Eliasson, B., Gudbjörnsdottir, S., & Swedish
National Diabetes Register. (2009). Effect of tight control of HbA1c and blood pressure on
cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National
Diabetes Register (NDR). Diabetes Research and Clinical Practice, 86(1), 74–81.
https://doi.org/10.1016/j.diabres.2009.07.003
Metcalf, P. A., Kyle, C., Kenealy, T., & Jackson, R. T. (2017). HbA1c in relation to incident diabetes and
diabetes-related complications in non-diabetic adults at baseline. Journal of Diabetes and Its
Complications, 31(5), 814–823. https://doi.org/10.1016/j.jdiacomp.2017.02.007
Rawshani, A., Rawshani, A., Franzén, S., Sattar, N., Eliasson, B., Svensson, A.-M., … Gudbjörnsdottir, S.
(2018). Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The
New England Journal of Medicine, 379(7), 633–644. https://doi.org/10.1056/NEJMoa1800256
Zhao, W., Katzmarzyk, P. T., Horswell, R., Wang, Y., Johnson, J., & Hu, G. (2014). Sex differences in the
risk of stroke and HbA(1c) among diabetic patients. Diabetologia, 57(5), 918–926.
https://doi.org/10.1007/s00125-014-3190-3