Hypertension and diabetes mellitus are not contagious diseases, have a high prevalence, and often occur together. In patients with diabetes mellitus, hypertension occurs two times more often than without diabetes, and the prevalence reaches 80%. The presence of these two diseases together, more commonly found in patients with obesity and old age.

Hypertension Management in Diabetic Patient
Image Source: www.klikdokter.com

Hyperglycemia accelerates the formation of atherosclerotic lesions. Therefore, diabetic patients have a 2-fold higher risk of cardiovascular disease than patients without diabetes. 

Although diabetes is associated with an increased risk of heart disease, the Framingham cohort study showed this increased risk occurs due to the coexistence of hypertension. The presence of diabetes and hypertension simultaneously causes an increased risk of coronary heart disease, left ventricular hypertrophy, heart failure, stroke, retinopathy, and nephropathy, up to 4 times greater when compared to patients without hypertension and diabetes.

Controlling blood pressure in hypertensive patients with diabetes is more complicated than without diabetes. Based on the results of the EUROASPIRE IV survey, only 54% of diabetic patients achieved blood pressure targets <140/90 mmHg. This was due to the presence of autonomic neuropathy, which causes interference with nocturnal blood pressure reduction, increased heart rate, and high blood pressure variability. 

When should antihypertensive drug treatment be initiated in diabetic patients?

Based on the latest recommendations from the American College of Cardiology (ACC) / American Heart Association (AHA) in 2017, hypertension is defined as blood pressure ≥130 / 80 mmHg. Patients included in the hypertension criteria need to be identified with the risk of cardiovascular disease within 10 years.

In patients with a risk of <10%, blood pressure control can be done by lifestyle modification. Whereas in patients with a high risk of cardiovascular disease (> 10%), including patients with diabetes, the antihypertensive drug is given at blood pressure ≥130 / 80 mmHg in addition to lifestyle modification.

In contrast to the American Diabetic Association (ADA) 2017 recommendations, hypertension is defined as blood pressure ≥140 / 90 mmHg. Therefore, antihypertensive administration in patients with diabetes is recommended if blood pressure is ≥140 / 90 mmHg.

The epidemiological analysis showed an increase in blood pressure ≥115 / 75 mmHg was associated with an increased incidence of cardiovascular disease, heart failure, retinopathy, kidney disease, and mortality. So,  blood pressure control is very important in influencing the clinical outcome of patients with diabetes mellitus.

One of the considerations in initiating antihypertensive therapy in diabetic patients is orthostatic hypotension. This condition is defined as a decrease in systolic blood pressure of 20 mmHg or diastolic 10 mmHg in 3 minutes on standing measurements compared to the results of blood pressure measurements when sitting or lying down. Orthostatic hypotension commonly occurs in patients with diabetes mellitus due to the neuropathy process of the autonomic nervous system. Therefore, in blood pressure that is not too high, the use of antihypertensive can worsen symptoms. Orthostatic hypotension is also associated with an increased risk of death and heart failure. 

Which antihypertensive drug is best for diabetics?

2017 ADA Guidelines Recommendations

Patients with blood pressure ≥140 / 90 mmHg should take the antihypertensive drug in addition to lifestyle modification. The administration antihypertensive drug starts with 1 type of drug and is titrated until it reaches the target blood pressure.

Patients with blood pressure ≥160 / 100 mmHg should start antihypertensive treatment with titration of two drugs or one combination preparation, in addition to lifestyle modification. Aggressive therapy is given to reduce cardiovascular events.

The recommended antihypertensive drugs types are:

  • ACE inhibitors (ACEi), 
  • angiotensin receptor blockers (ARBs), 
  • thiazide-like diuretics, 
  • calcium channel blockers (CCBs) dihydropyridine type. 

If the target of reducing blood pressure fails to be achieved, use these drugs combination, except for the combination of ACEi and ARB. The combination of ACEi and ARB increases the risk of hyperkalemia, fainting, and acute kidney damage.

The research compared the use of ACEi plus CCB dihydropyridine with the use of ACEi alone in diabetic patients with blood pressure ≥160 / 100 mmHg. It showed that within 3 months, 63% of patients with ACEi and CCB dihydropyridine managed to achieve the therapeutic target. Only 37% of patients with ACEi alone succeeded in reaching the target blood pressure (p = 0.002).

Another study comparing the use of ACEi plus thiazide-like diuretics with only ACEi in patients with blood pressure ≥160 / 95 mmHg showed a significant increase in the proportion of successful blood pressure control in 6 months in the drug combination group compared to the group with ACEi alone (65% vs. 53 %, p = 0.026)

Use ACEi or ARB up to the maximum tolerable dose, be first-line therapy in diabetic patients with renal impairment (ratio of urine albumin and creatinine ≥300 mg / g), or albuminuria (excretion of albumin ≥30 mg / g creatinine) to prevent worsening renal impairment.
Monitoring of fluid adequacy, serum creatinine levels, renal, and potassium filtration rates need to be done in diabetic patients using ACEi, ARB, or diuretics.

In patients with a history of orthostatic hypotension, the use of alpha-blockers and diuretics should be avoided. In addition, drug delivery time can be adjusted, for the example given at night. The use of stockings can also reduce the onset of symptoms.

ACC / AHA 2017 Guidelines Recommendations.

  1. Antihypertensive drugs recommended are first-line drugs are ACEi, ARB, dihydropyridine CCH, and diuretics.
  2. In patients with diabetes and hypertension with albuminuria, ACEi, and ARB are the first choices.

What levels should systolic blood pressure be lowered?

The American Diabetes Association (ADA) recommends a target reduction in blood pressure in diabetic patients at least <140/90 mmHg, whereas the 2017 ACC / AHA guidelines recommend a lower target of <130/80 mmHg. A meta-analysis of 73,913 diabetic subjects reported a 39% reduction in stroke incidence in systolic blood pressure <130 mmHg.

Another study titled ACCORD BP shows controlling blood pressure intensively does not reduce cardiovascular events significantly, but reduces the risk of stroke by 41%. Some other studies, HOT and SPRINT, have shown similar results that intensive blood pressure lowering in a group of patients with diabetes up to <130/80 mmHg can reduce the risk factors for cardiovascular disease events.

The ADA guidelines have also stated that a more intensive blood pressure reduction target (<130/80 or <120/80 mmHg) can be beneficial in a large population of diabetic patients with hypertension, especially those who have a previous history of cardiovascular disease.

Although it is considered capable of reducing the risk of cardiovascular disease, lower therapeutic targets also have side effects that increase the risk of electrolyte imbalances, and acute kidney disease.

Setting too low blood pressure targets increases the risk of orthostatic hypotension. Therefore, setting blood pressure targets must be made personally based on the condition of each patient.

The presence of diabetes and hypertension together causes an increased risk of coronary heart disease, left ventricular hypertrophy, heart failure, stroke, retinopathy, and nephropathy up to two times compared to patients with one condition alone.
In diabetic patients with hypertension, the administration of antihypertensive medications starts at blood pressure ≥130 / 80 mmHg despite lifestyle modification.
The recommended antihypertensive drugs are ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), thiazide-like diuretics, or dihydropyridine type calcium channel blockers (CCBs).
ACEi and ARB are the first choices for diabetics patients with hypertension and albuminuria.
ACC / AHA 2017 recommendations target blood pressure in diabetic patients is <130/80 mmHg.

1. A. Grossman, E. Grossman, Cardiovasc Diabetol , 2017,16(3). https://cardiab.biomedcentral.com/articles/10.1186/s12933-016-0485-3
2. T.A. Aksnes, S.N.Skarn, S.E. Kjeldsen, Expert Rev. Cardiovasc. Ther, 2012, 10(6), 727–734. http://www.tandfonline.com/doi/full/10.1586/erc.12.59
3. P.K. Whelton, R.M. Carey, et al., hypertension, 2017, 00,000-000. http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf
4. I.H. de Boer, S. Bangalore, A. Benetos, A.M. Davis, E.D. Michos, P. Muntner, et al, Diabetes Care, 2017,40,1273–1284. http://care.diabetesjournals.org/content/diacare/40/9/1273.full.pdf
5. G. Reboldi , G. Gentile, F. Angeli , et al, J Hypertens, 2011,29,1253-1269. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0032392/
6. W.C. Cushman, G.W. Evans, R.P. Byington, et al., N Engl J Med, 2010, 362, 1575-1585. http://www.nejm.org/doi/full/10.1056/NEJMoa1001286
7. V. Perkovic, A.Rodgers, N Engl J Med, 2015, 373, 2175-2178. http://www.nejm.org/doi/full/10.1056/NEJMe1513301